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8th International Congress
The Queen Elizabeth II Conference Centre, London, UK
www.psoriasisg2c.com
Programme & Abstracts 30th November – 2nd December 2017
PSORIASISfrom gene to clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.com
3
CO-CHAIRS
Jonathan Barker London, UK Christopher Griffiths Manchester, UK
LOCAL ORGANISING COMMITTEE
David Burden Edinburgh, UKCatherine Smith London, UKRichard Warren Manchester, UK SCIENTIFIC COMMITTEE
Hervé Bachelez Paris, France James Elder Ann Arbor, USAMichel Gilliet Lausanne, Switzerland Lars Iversen Aarhus, DenmarkAlexa Kimball Boston, USA James Krueger New York, USAAlan Menter Dallas, USA Errol Prens Rotterdam, The Netherlands Jörg Prinz Munich, GermanyPeter van de Kerkhof Nijmegen, The Netherlands
ORGANISING SECRETARIAT
Psoriasis from Gene to ClinicConference and Events ServicesBritish Association of Dermatologists4 Fitzroy SquareLondon W1T 5HQ, UK
Tel: +44 (0) 20 7391 6358
Email: [email protected]: www.psoriasisg2c.com
PSORIASIS FROM GENE TO CLINIC
8TH INTERNATIONAL CONGRESSTHE QUEEN ELIZABETH II CONFERENCE CENTRE, LONDON, UK
PROGRAMME & ABSTRACTS BOOK
PSORIASISfrom gene to clinic
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Welcome 3
Congress Information 4- 5
Thursday Scientific Programme 6 - 7
Friday Scientific Programme 8 - 11
Saturday Scientific Programme 12 - 13
Poster Presentations 14 - 25
Invited & Keynote Lecturers Abstracts 26 - 55
Free Communication Abstracts 56 - 71 Poster Abstracts 72 - 128 Author Index 129 - 133
CONTENTS
WELCOME
The outlook for patients with psoriasis has never been better. New medicines are being introduced into clinical practice that offers the prospect of long-term disease control. These advances are built upon significant insights into the immunopathogenesis of psoriasis and how it potentially relates to other conditions. But there is much more that needs to be done. For example, can immunology and genetics provide insight into the mechanisms underlying different forms of psoriasis? Can these insights translate into more targeted therapy for patients? How close are we to delivering the right treatment for the right patient at the right time?
Building on the success of our previous International Congresses, held every three years over the past 21 years, Psoriasis: from Gene to Clinic is designed to provide a forum for experts from around the world to present and discuss cutting edge issues. Delegates are anticipated to include clinicians, scientists and members of the biotechnology and pharmaceutical industries. The Congress will be entirely plenary allowing attendees to listen to all invited and submitted oral presentations and meet all poster presenters. The programmed sessions will be dedicated to key areas of current scientific and clinical interest ranging from genetics and immune mechanisms to comorbidities and therapeutics. Stratification approaches to both the diagnosis and treatment of psoriasis will feature prominently. The scientific programme will include invited lectures from experts drawn predominantly from outside dermatology. These will include keynote lectures given by two internationally renowned experts: Professor Sir John Savill, London, UK and Dr Leroy Hood, Seattle, USA. Between these presentations there will be free communications chosen from submitted abstracts. Each day will feature sponsored lectures, poster presentations and opportunity for informal discussions.
The high quality of the meeting is reflected in our choice of venue. The Queen Elizabeth II Conference Centre is uniquely situated in the shadow of Big Ben and Westminster Abbey. The welcome reception will take place at the Conference Centre and the Congress Dinner will be held at the magnificent Natural History Museum, a unique, historic venue in the heart of London.
Winter is an excellent time to visit London and we look forward to welcoming you.
Jonathan N W N Barker Christopher E M GriffithsSt John’s Institute of Dermatology The Dermatology CentreKings College London, UK University of Manchester, UK
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NOTES FOR SPEAKERS AND POSTER PRESENTERS
The Speaker Preview Room will be located in the East Long room on the third floor. It is essential to the smooth running of the Congress that all speakers take their presentation to the Speaker Preview Room as soon as possible after their arrival at the Congress Venue but not later than 1 hour before the beginning of their session.
SCIENTIFIC POSTER DISPLAY
The scientific poster display will be situated in the Whittle Room on the third floor. The poster area will be available for presenters to mount their posters from 07:30 on Thursday 30th November. Posters are to be removed by 14:00 on Saturday 2nd December. Presenters of odd numbered posters are asked to be at their poster sites for discussion from 12:45 to 13:45 on Thursday 30th November and those with even numbers between the times of 12:15 to 13:15 on Friday 1st December.
AWARDS FOR BEST POSTER AND BEST ORAL PRESENTATION
Awards will be made to the presenters of the best oral and best poster presentation. The presentation of these awards will be made at the end of the last Congress session on Saturday 2nd December.
WELCOME RECEPTION
THURSDAY 30TH NOVEMBER 17:00 - 19:30
A welcome drinks reception will be held in the Britten Room at The Queen Elizabeth II Conference Centre at the end of the day’s scientific sessions on Thursday 30th November. All registered delegates are invited to attend. We hope this will be a perfect opportunity to relax, catch up with old acquaintances and form new friendships.
CONGRESS DINNER
FRIDAY 1ST DECEMBER 19:30 - 23:00
The Congress Dinner will be held at The Natural History Museum. With its outstanding history, the Natural History Museum is an iconic building in the heart of London. With many galleries, collections, paintings and incredible design it remains an outstanding slice of British history. A splendid three course meal will take place in the magnificent Central Hall, the home of the blue whale skeleton.
Tickets should have been purchased in advance when registering and can be found in your delegate pack.
Dress Code: Business or lounge suit
CONGRESS INFORMATION
Transport for the dinner will depart from and return to the Queen Elizabeth II Conference Centre. Coaches will depart at 19:00.
CERTIFICATES OF ATTENDANCE
Certificates of attendance can be found in your delegate pack.
CLOAKROOM
The Cloakroom is located on the Ground Floor.
CPD CREDITS
Psoriasis: from Gene to Clinic has been approved for 15 credits by the Royal College of Physicians, approval number 115363. All physicians registered for CPD must record their attendance hours in accordance with the guidelines given by the RCP.
LUNCH AND REFRESHMENTS
Lunch and refreshments as indicated in the Programme are included in your registration fee.
PROFESSIONAL & PATIENT ORGANISATIONS
The following professional organisations, patient support groups, charities and psoriasis research programmes will be represented at the Congress:
International Psoriasis CouncilThe Psoriasis AssociationThe Psoriasis and Psoriatic Arthritis Alliance British Skin FoundationBritish Association of Dermatologists Biologic Interventions Register (BADBIR)The International League of Dermatological Societies (ILDS)UK TREND
REGISTRATION
Tel: +44 (0)20 7798 4091
The registration desk will be staffed between the following hours:
Thursday 30th November 07:30 – 17:30Friday 1st December 07:30 – 17:30Saturday 2nd December 08:00 – 13:30
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THURSDAY 30TH NOVEMBER 2017
07:30 Registration opens
10:00 – 10:15 Welcome and Introduction J. Barker (London, UK) C. Griffiths (Manchester, UK)
SCIENTIFIC SESSION 1Chairs: H. Bachelez (France), E. Prens (The Netherlands)
10:15 – 10:25 FC – 1 Psoriasis and risk of malignant lymphoma: a population-based cohort study M. Kamstrup, L. Skov, C. Zachariae, J. Thyssen and A. Egeberg
10:25 – 10:35 FC - 2 Developing a therapeutic range and predicting response to biologics in patients with psoriasis: a multicentre prospective observational cohort study T. Tsakok and the PSORT Consortium 10:35 – 10:45 FC - 3 The differential production of interleukin (IL)-26 vs. IL-17 by T helper 17 cells contributes to the development of different forms of psoriasis A. Fries, J. Di Domizio, O. Demaria and M. Gilliet
10:45 – 11:15 Invited speaker The human skin microbiome and implications for disease B. Andersson (Stockholm, Sweden)
11:15 – 11:45 Coffee break
11:45 – 11:55 FC – 4 Psoriasis-associated late cornified envelope proteins have antibacterial activity H. Niehues, L. Tsoi, D. van der Krieken, P. Jansen, M. Oortveld, D. Rodijk-Olthuis, I. van Vlijmen-Willems, W. Hendriks, R. Helder, J. Bouwstra, R. Mesman, L. van Niftrik, E. van den Bogaard, P. Stuart, R. Nair, J. Elder, P. Zeeuwen and J. Schalkwijk
11:55 – 12:05 FC – 5 Environmental antigens may trigger HLA-C*06:02-mediated autoimmunity in psoriasis Y. Arakawa, A. Arakawa, S. Vural, A. Galinski, S. Vollmer and J. Prinz
12:05 – 12:15 FC – 6 Analysis of psoriasis host-microbiome interactions using a universal transcriptomic approach T. Furnholm, M. Foo, J. Henderson, K. Shedden and A. Johnston
THURSDAY PROGRAMME
12:15 – 12:45 Invited speaker Induction and regulation of Th17 Cells V. Kuchroo (Boston, USA)
12:45 – 13:45 Lunch and poster viewing
SCIENTIFIC SESSION 2Chairs: R. Warren (UK), C. Smith (UK)
13:45 – 13:55 FC – 7 Genetic variation contributes to response to biologics: initial findings of the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium N. Dand on behalf of the PSORT consortium
13:55 – 14:05 FC – 8 Comparative evaluation of cellular and molecular changes associated with response to selective interleukin (IL)-23 blockade vs. dual IL-12/23 blockade in psoriasis skin K. Li, K. Campbell, S. Garcet, C. Brodmerkel and J. Krueger
14:05 – 14:15 FC – 9 Functional immunophenotyping analysis reveals adalimumab-induced impairment of tumour necrosis factor signalling in lymphoid cells in psoriasis R.A. Ejarque on behalf of the PSORT consortium
14:15 – 15:00 Keynote lecture The importance of academic-industrial collaboration to the future of medical research J. Savill (London, UK)
15:00 – 15:45 Tea break
15:45 – 16:15 Lilly Sponsored lecture Targeting IL-17: findings from recent clinical trials A. Blauvelt (Portland, USA) This presentation has been organised and funded by Lilly, Lilly products will be discussed in this session.
16:20 – 16:50 Almirall Sponsored lecture The epidemiology and interrelation of psoriasis and other IL-23 related diseases A. Kimball (Boston, USA)
17:00 – 19:30 Welcome Reception The Queen Elizabeth II Conference Centre
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FRIDAY 1ST DECEMBER 2017
SCIENTIFIC SESSION 3Chairs: J. Elder (USA), M. Gilliet (Switzerland)
08:00 – 08:30 LEO Pharma Sponsored lecture Pro-inflammatory redundancy in the IL-17 pathway - the role of the individual IL-17 cytokine family members in psoriasis J. Krueger (New York, USA)
08:35 – 09:05 Janssen Sponsored lecture IL-23 inhibition as a strategy to treat immune-mediated inflammatory diseases J. Prinz (Munich, Germany) & S. Danese (Milan, Italy)
09:05 – 09:15 FC – 10 The genetic basis for most patients with pustular skin disease remains elusive U. Hüffmeier, S. Löhr, P. Schulz, A. Körber, J.C. Prinz, K. Schäkel, S. Philipp, K. Reich, H. Ständer, A. Jacobi, K. Kingo, S. Koks, S. Gerdes, T. Schill, K.G. Griewank, S. Frey, K. Steinz, S. Uebe, M. Sticherling, H. Sticht, P. Gkogkolou, V. Oji, D. Wilsmann-Theis and R. Mössner 09:15 – 09:25 FC – 11 ADAM17 and TIMP3 are psoriasis-relevant checkpoints controlling T helper 17 programming by inflammatory dermal dendritic cells A. Kunze, A. Rendon, S. Oehrl, G. Murphy, A. Enk and K. Schäkel
09:25 – 09:35 FC – 12 Genotype and phenotype analyses revealed novel susceptibility genes and new clinical classification for psoriasis B.-J. Feng, S. McCarthy, H. Li, K. Praveen, J. Walsh, J. Hawkes, M. Milliken, D. Goldgar, J. Reid, J. Overton, F. Dewey, C. Gonzaga-Jauregui, S. Guthery, K. Callis Duffin and G. Krueger
09:35 – 09:45 FC – 13 Advances in genomic studies of psoriasis in China X. Zhang
09:45 – 10:15 Invited speaker From GWAS to systematic host-microbiome association studies in complex immune-mediated diseases A. Franke (Kiel, Germany)
10:15 – 10:45 Coffee break
FRIDAY PROGRAMME
Chairs: L. Iversen (Denmark), J. Krueger (USA)
10:45 – 10:55 FC – 14 iRhom2: a mechanistic hub in keratinocyte hyperproliferation and psoriasis? M. Brooke, T. Maruthappu, A. Chikh and D. Kelsell
10:55 – 11:05 FC – 15 Identifying chromatin interactions between psoriasis-associated variants and target genes using Capture Hi-C Helen Ray-Jones, A. McGovern, P. Martin, K. Duffus, S. Eyre and R.B. Warren
11:05 – 11:15 FC – 16 The psoriasis-associated Act1(D10N) variant reduces responses to interleukin-17 but enhances T helper 17 responses to polyclonal activation S. Lambert, C. Hambro, A. Johnston, R. Nair and J. Elder
11:15 – 11:25 FC - 17 ERAP1 risk variants in psoriasis vulgaris affect autoantigen presentation A. Arakawa, S. Vollmer, E. Reeves, E. James and J.C. Prinz
11:25 – 11:55 Invited speaker Functional variation in the human genome: lessons from the transcriptome T. Lappalainen (New York, USA) 11:55 – 12:05 FC – 18 Tumour necrosis factor blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis C. Conrad, J. Di Domizio, A. Mylonas, O. Demaria, C. Belkhodja, A. Navarini, A.-K. Lapointe, L. French, M. Vernez and M. Gillliet
12:05 – 12:15 FC – 19 Activation of resident T cells in resolved psoriasis reveals tissue responses that stratify clinical outcome I.G. Sérézal, C. Classon, S. Nylén, N.X. Landén, E. Martini, S. Cheuk and L. Eidsmo 12:15 – 13:15 Lunch and poster viewing
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FRIDAY 1ST DECEMBER 2017 CONTINUED
SCIENTIFIC SESSION 4Chairs: A. Kimball (USA), D. Burden (UK)
13:15 – 13:25 FC – 20 Longitudinal follow-up of arterial structure and function in patients with severe psoriasis treated by anti-interleukin (IL)-12/IL-23 agents compared with tumour necrosis factor inhibitors M. Viguier, H. Khettab, I. Hamdidouche, P. Boutouyrie and H. Bachelez
13:25 – 13:35 FC – 21 Real-world experience with apremilast in patients with psoriasis: interim analysis of 104 patients from the APPRECIATE study E. Kleyn, M. Radtke, C. Bundy, K. Eyerich, M. Ståhle, M. Cordey, V. Koscielny, C.E.M. Griffiths and M. Augustin
13:35 – 13:45 FC - 22 Topical methotrexate gold nanoparticles reduce imiquimod-induced inflammation in mice A. Özcan, D. Bunton, G. Macluskie, M. Duric, J. Barry and A. Kolios
13:45 – 13:55 FC - 23 Efficacy and safety of secukinumab in patients who have failed antitumour necrosis factor-α treatment from the U.K. and Republic of Ireland: results of the SIGNATURE study R.B. Warren, J. Barker, D. Burden, A. Finlay, C. Hatchard, P. Jeffery, R. Williams and C.E.M. Griffiths
13:55 – 14:25 Invited speaker Why biologics fail A. Gils (Leuven, Belgium)
14:25 – 15:10 Tea break
FRIDAY PROGRAMME CONTINUED
SCIENTIFIC SESSION 5Chairs: P. Van de Kerkhof (The Netherlands), H. Bachelez (France) 15:10 – 15:20 FC – 24 The genetic analysis of a large pustular psoriasis resource highlights differential effects for IL36RN and AP1S3 mutations S. Twelves, K. Farkas, S.E. Choon, D. Burden, C.E.M. Griffiths, A. Irvine, E. Tan, M. Szell, Z. Bata-Csorgo, C. Smith, F. Capon and J. Barker
15:20 – 15:30 FC – 25 Transcriptomic profiling of interleukin (IL)-36A, IL-36B and IL-36G cytokine responses in keratinocytes demonstrates a high degree of overlap and dependency on MYD88 and nuclear factor-kB signalling W. Swindell, M. Sarkar, M. Beamer, X. Xing, M. Kahlenberg, N. Ward, J. Voorhees, L. Tsoi, Y. Liang and J. Gudjonsson
15:30 – 16:00 Invited Lecture Biology and pathology of IL-36 J. Towne (San Diego, USA) 16:05 – 16:35 AbbVie Sponsored lecture The evolution of T cell targeted therapy in psoriasis J. Barker (London, UK)
16:40 – 17:10 UCB Pharma Sponsored lecture Re-evaluating the role of IL-17F in immune-mediated chronic inflammation: dual neutralisation of both IL-17A and IL-17F as a novel targeting approach in psoriatic diseases S. Shaw (Slough, UK)
19:30 – 23:00 Congress Dinner The Natural History Museum
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SATURDAY 2ND DECEMBER 2017
SCIENTIFIC SESSION 6Chairs: A. Menter (USA), J. Prinz (Germany)
08:40 – 09:10 Novartis Sponsored lecture Disease modification, from bedside to bench L. Iversen (Aarhus, Denmark) & L. Eidsmo (Stockholm, Sweden)
09:15 – 09:45 Celgene Sponsored lecture The complex management of patients with psoriasis and comorbidities: the role of therapy choice P. Gisondi (Verona, Italy)
09:45 – 09:55 FC – 26 Effectiveness, drug survival and safety of fumaric acid esters for moderate-to-severe psoriasis in routine care: results from the German Psoriasis Registry PsoBest M. Augustin, U. Mrowietz, M.A. Radtke, D. Thaci, K. Ralph, A. Körber and K. Reich
09:55 – 10:05 FC - 27 The lymphatic system plays an important role in the migration of pathogenic T cells towards synovial joints and entheses in psoriasis D. Verhaegh, E. Prens, A.M.C. Mus, P.S. Asmawidjaja, N. Davelaar, A. Hofman, J.-B. Jaquet, J.M.W. Hazes, M.R. Kok, E. Lubberts and R.J. Bisoendial
10:05 – 10:15 FC – 28 Systemic inflammation and evidence of a cardiosplenic axis in patients with psoriasis K.F. Hjuler, L.C. Gormsen, M.H. Vendelbo, A. Egeberg, J. Nielsen and L. Iversen
10:15 – 10:45 Invited Lecture Challenging conventional classification dogma: towards a new clinical taxonomy of psoriasis U. Mrowietz (Kiel, Germany)
10:45 – 11:15 Coffee Break
SATURDAY PROGRAMME
Chairs: J. Barker (UK), C. Griffiths (UK)
11:15 – 11:25 FC – 29 Efficacy and safety of risankizumab, an interleukin-23 inhibitor, in patients with moderate-to-severe chronic plaque psoriasis: 16-week results from the phase III IMMhance trial A. Blauvelt, K.A. Papp, M. Gooderham, R.G. Langley, C. Leonardi, J.-P. Lacour, S. Philipp, S. Tyring, M. Bukhalo, J.J. Wu, J. Bagel, E.H. Frankel, D. Pariser, M. Flack, J. Scherer, Z. Geng, Y. Gu, A. Camez and E.H.Z. Thompson
11:25 – 11:35 FC – 30 Quality of care and use of systemic drugs for psoriasis in the past 12 years: results from a series of nationwide health care studies in Germany M. Radtke, M. Augustin and K. Reich
11:35 – 12:05 Invited Lecture The price and value of biologic drugs J. Scannell (Edinburgh, UK) 12:05 – 12:15 FC – 31 Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a phase II study K. Reich, R. Bissonnette, A. Menter, P. Klekotka, D. Patel, J. Li, J. Tuttle and K. Papp 12:15 – 12:25 FC – 32 Certolizumab pegol for the treatment of patients with moderate-to-severe chronic plaque psoriasis: an overview of three randomized controlled trials A. Blauvelt, K. Reich, M. Lebwohl, D. Burge, C. Arendt, L. Peterson, J. Drew, R. Rolleri and A. Gottlieb 12:25 – 12:35 FC – 33 Switching or restarting of tumour necrosis factor-α inhibitors after interruption under daily-life conditions: efficacy report from the Austrian Psoriasis Registry (PsoRA) P. Wolf, W. Weger, L. Richter, A. Mlynek, P. Sator, W. Saxinger, G. Ratzinger, C. Kölli, C. Painsi, C. Bangert, R. Tatarski, M. Schütz-Bergmayr, P. Ponholzer, F. Trautinger, R. Strohal, R. Müllegger, M. Inzinger, R. Lichem, W. Salmhofer and F. Quehenberger
12:35 – 13:20 Keynote lecture Systems Medicine, Big Data and Scientific Wellness are Transforming Healthcare L. Hood (Seattle, USA) 13:20 Presentation of best oral and best poster prize C. Griffiths (Manchester, UK) J. Barker (London, UK)
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30TH NOVEMBER – 2ND DECEMBER 2017
THE QUEEN ELIZABETH II CONFERENCE CENTRE – WHITTLE ROOM
P – 1 Evaluation of serum uric acid among patients with psoriasis in a developing country S.D. Joshi and L. Limbu
P – 2 A transcriptomic study investigating the pathogenesis of generalized pustular psoriasis M. Catapano, F. Capon, F. Ciccarelli and J. Barker
P – 3 Patient perception and the importance of clear/almost clear skin as a treatment goal in moderate-to-severe plaque psoriasis: results of the ‘Clear about Psoriasis’ worldwide patient survey A. Armstrong, S. Jarvis, W.-H. Boehncke, M. Rajagopalan, P. Fernández-Peñas, R. Romiti, A. Bewley, M. O’Donnell, L. Huneault, E. Dekker, M. Sodha and R.B. Warren
P – 4 Immunogenicity with tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, in a pooled analysis of three randomized controlled trials in patients with chronic plaque psoriasis A. Kimball, A. Blauvelt, K. Reich, Q. Li, F. van Aarle, T. Kerbusch and D. Montgomery
P – 5 Next-generation sequencing identifies epidermal microRNAs deregulated in psoriasis skin A. Srivastava, L. Pasquali, F. Meisgen, M. Stahle, N.X. Landén, A. Pivarcsi and E. Sonkoly
P – 6 Effect of adipose-derived stem cells on an imiquimod-induced psoriasiform mouse model by hypodermic injection J. Deng, C. Lu, L. Han and Y. Huang
P – 7 Impairment of gustatory and olfactory senses in plaque psoriasis P. Rüter, V. Grünthaler, Y. Zopf and M. Sticherling
P – 8 Psoriasis in children: a single-centre analysis F. Heppt, J. Raap and M. Sticherling
P – 9 Interleukin-36γ detection via noninvasive tape stripping reliably diagnoses psoriasis A. Keszegpal, A. Latzko, G. Brown, M. Goodfield, P. Laws, T. Macleod, J. Ainscough, A. Alase, D. Reid, J. Wenzel, P. Helliwell, M. Stacey and M. Wittmann
P – 10 Caffeine in the treatment of atopic dermatitis and psoriasis: a review M. Alashqar1 and N. Goldstein
POSTER PRESENTATIONS
P – 11 Population pharmacokinetic modelling of tildrakizumab (MK-3222), an anti-interleukin-23-p19 monoclonal antibody, in healthy volunteers and patients with psoriasis P. Jauslin, P. Kulkarni, R. Wada, S. VataKuti, A. Hussain, L. Wenning and T. Kerbusch
P - 12 Poster withdrawn.
P – 13 Immune modulation by topical PH-10 aqueous hydrogel (rose Bengal disodium) in psoriasis lesions J.G. Krueger, S. Garcet, J. Fuentes-Duculan, N. Kunjravia, I. Cueto, X. Li, J.M. Singer and E.A. Wachter
P – 14 Favourable safety profile of ixekizumab: results from 11 moderate-to-severe psoriasis and three psoriatic arthritis clinical trials A. Gottlieb, K. Papp, W. Xu, L. Mallbris and N. Agada
P – 15 Poster withdrawn.
P - 16 Cytokine effects of apremilast as a mechanism of efficacy in systemic-naive patients with moderate plaque psoriasis: results from the UNVEIL trial B. Strober, M. Alikhan, B. Lockshin and P. Schafer
P – 17 Patient- and physician-reported outcomes with apremilast for patients with plaque psoriasis during routine dermatology care in Germany: an interim analysis K. Reich, S. Bomas, B. Korge, M. Manasterski, U. Schwichtenberg, H. Mentz, K. Groegel and N. Núnez Gómez
P - 18 Shear wave elastography in patients on high-dose methotrexate: a prospective study D. Kivelevitch, R. Rahimi and A. Menter
P – 19 Do patients with certain human leucocyte antigen expression have a higher risk of developing psoriasis? A. Anandan, K. Radhakrishnan, R. Prasada and V.K. Panicker
P – 20 Utility study to map utilities to the Psoriasis Area and Severity Index and Dermatology Life Quality Index instruments in patients with chronic plaque psoriasis C. Baker, J. Sullivan, P. Davey and J. Wilson
P – 21 Secukinumab shows high and sustained efficacy in nail psoriasis: 2.5-year results from the TRANSFIGURE study K. Reich, P. Arenberger, U. Mrowietz, S. Jazayeri, M. Augustin, A. Parneix, P. Regnault, R. You and J. Frueh
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P - 22 Secukinumab pooled and long-term safety: analysis of 19 psoriasis clinical trials P. van de Kerkhof, K. Reich, C. Leonardi, A. Blauvelt, N. Mehta, T.-F. Tsai, R. You, P. Papanastasiou, M. Milutinovic and C.E.M. Griffiths
P – 23 Lysosomal action in the regulation of inflammatory processes on the example of psoriasis K. Bocheńska, M. Moskot, E. Smolińska, J.J.-Banecka and M. Gabig-Cimińska
P – 24 Secukinumab demonstrates significantly lower immunogenicity potential than ixekizumab in human in vitro assays S. Spindeldreher, B. Maillère, E. Correia, M. Tenon, A. Karle, P. Jarvis and F. Kolbinger
P – 25 Decreased expression of interleukin-27 in moderate-to-severe psoriasis and its anti- inflammatory role in an imiquimod-induced psoriasis-like mouse model W. Chen, Y. Gong, X. Zhang, Y. Tong, X. Wang, C. Fei, H. Xu, Q. Yu, Y. Wang and Y. Shi
P – 26 Secukinumab shows high and sustained efficacy in patients with moderate-to-severe palmoplantar psoriasis: 2.5-year results from the GESTURE study A. Gottlieb, J. Sullivan, A. Kubanov, R. You, P. Regnault and J. Frueh
P - 27 Efficacy and safety of infliximab in the treatment of the Chinese patients with psoriasis J.-Z. Guo, W.-H. Wang and C.-L. Zhang
P – 28 Secukinumab clinical outcomes in a tertiary referral centre O. Jagun, S.T. Cheung, O. Jagun and S.T. Cheung
P – 29 Sustained response to adalimumab over multiple years in patients with plaque psoriasis: analyses from the British Association of Dermatologists Biologic Interventions Register (BADBIR) B. Kirby, J.-F. Maa, T. Festini, B. Calimlim and O.R. Servín
P - 30 Successful treatment of psoriasis with secukinumab after ustekinumab in a patient with multiple sclerosis S. Kaneko, H. Oguro and E. Morita
P – 31 Development of pulmonary sarcoidosis in a patient with psoriasis under treatment with ustekinumab: comorbidity or drug-related ‘paradoxical’ phenomenon? C. Fotiadou, E. Lazaridou, E. Sotiriou and D. Ioannides
POSTER PRESENTATIONS CONTINUED
P – 32 Factors associated with the choice of the first biologic in psoriasis: real-life analysis from the Psobioteq cohort E. Sbidian, C. Giboin, H. Bachelez, C. Paul, M. Beylot-Barry, A. Dupuy, M. Viguier, J.-P. Lacour, J.-L. Schmutz, P. Bravard, E. Mahé, N. Beneton, L. Misery, E. Delaporte, P. Modiano, S. Barbarot, S. Régnier, D. Jullien, M.-A. Richard, P. Joly, F. Tubach and O. Chosidow
P – 33 The Psoriasis Association as a role model for other support groups: how far can (dare) we go? H.H. Oon
P – 34 Paradoxical psoriasis caused by tumour necrosis factor inhibitor therapy: a model system to study the interplay between environmental triggers and genetic susceptibility? T. Maruthappu, A. Connolly, S. Mahil, B. Kirkham, P. DiMeglio and C. Smith
P – 35 The coexistence of generalized pustular psoriasis and pemphigus foliaceus in a woman with Cushing syndrome: a case report A. Kusumawardani, S.E. Ilona, D.A. Mira and Suradi Radiono
P – 36 Retrospective audit on psoriasis, assessment and management: National Institute for Health and Care Excellence guideline CG153 within a dermatology department M. Verma, A. Leong and S. Velangi
P – 37 Role of Thevetia neriifolia in the treatment of psoriasis: clinical case report D. Maryam, S. Souad, O.S. Charifa and S.-B. Rachida
P – 38 Large-scale imputation of killer cell immunoglobulin-like receptor copy number in psoriatic arthritis R. Ahn, D. Vukcevic, A. Motyer, D. Ellinghaus, L.C. Tsoi, R.P. Nair, C. Palmer, J. Oksenberg, J. Foerster, J.T. Elder, A. Franke, S. Leslie and W. Liao
P - 39 Psoriasis following PD-1 inhibitor therapy: features and treatment P. O’Connor and J.P. Dutz
P – 40 Evaluation of body composition in patients with psoriasis treated with ustekinumab M. Galluzzo, S. D’Adamio, R. Pastorino, L. Bianchi and M. Talamonti
P – 41 Characteristics and risk profile of patients with psoriasis included in the Turkish national registry PSR-TR N. Onsun, E.B. Baskan, D. Dizman, D.B. Ozkaya, A.C. Erkılıc, G. Ozarmagan and M.A. Gurer
P – 42 Treatment profile of patients with moderate-to-severe psoriasis included in the Turkish national registry PSR-TR N. Onsun, E.B. Baskan, D. Dizman, D.B. Ozkaya, A.C. Erkılıc, G. Ozarmagan and M.A. Gürer
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P - 43 An ongoing independent study to monitor the uptake of interleukin-17 inhibitors among U.S. dermatologists J. Robinson and L. Price
P – 44 Electronic monitoring of psoriasis outcomes and goals in practice: development and introduction of a standard dataset and a digital management system M. Augustin, J. Wimmer, M. Otten, V. Djamei, A. Navarini and M.A. Radtke
P – 45 Real-world data identify reasons for biological switching in patients with psoriasis J. Robinson and L. Price
P – 46 Comanagement with rheumatologists for patients with psoriatic arthritis receiving treatment with a biological agent or apremilast J. Robinson and L. Price
P – 47 Investigation of the role of IKKε role in the pathogenesis of psoriasis I. Weimar, L. Iversen and C. Johansen
P – 48 The interleukin-17A/F heterodimer regulates psoriasis-associated genes through IκBζ T. Bertelsen, C. Johansen and L. Iversen
P – 49 The psoriasis-associated interleukin-17A induces and cooperates with interleukin-36 cytokines to control keratinocyte differentiation and function C. Pfaff, Y. Marquardt, D. Kluwig, K. Fietkau, B. Lüscher and J. Baron
P – 50 Investigation of the efficacy and safety of acitretin treatment in children with pustular psoriasis X. Zhang, J. Liang and C. Li
P – 51 Real-world use of fumaric acid esters in psoriasis: results from the British Association of Dermatologists Biologic Interventions Register (BADBIR) K.J. Mason, M. Lunt, H.J. Hunter, Z.K. Jabbar-Lopez, B. Kirby, C.E. Kleyn, S. Kreppel, K. McElhone, N.J. Reynolds, R.B. Warren and C.E.M. Griffiths; on behalf of the BADBIR Study Group
P – 52 A real-world comparison of effectiveness and safety outcomes between clinical trial-eligible and -ineligible patients in the British Association of Dermatologists Biologic Interventions Register (BADBIR) K.J. Mason, J.N.W.N. Barker, C.H. Smith, P.J. Hampton, M. Lunt, K. McElhone, R.B. Warren, Z.Z.N. Yiu, C.E.M. Griffiths and A.D. Burden; on behalf of the BADBIR Study Group
POSTER PRESENTATIONS CONTINUED
P – 53 Guselkumab treatment provided higher frequency of complete skin clearance compared with adalimumab treatment among patients with moderate-to-severe plaque psoriasis P. Foley, M. Song, Y.-K. Shen, Y. You, Y. Wasfi and C.E.M. Griffiths
P - 54 Antibodies to guselkumab are not associated with reduction in clinical response or development of injection-site reactions in patients with moderate-to-severe plaque psoriasis Y. Zhu, J.C. Marini, Y. Wasfi, B. Randazzo, Y.-K. Shen, S. Li and H. Zhou
P – 55 Psoriasis Longitudinal Assessment and Registry (PSOLAR): description of demographic data from the Greek population upon full enrolment V. Chasapi, C. Antoniou, D. Rigopoulos, A. Roussaki-Schulze, D. Ioannides, I. Bassukas, W. Langholff and E. Soura
P – 56 Short-term reasons for withdrawal, and safety of apremilast as a monotherapy and combination therapy for psoriasis in clinical practice compared with clinical trials: a multicentre retrospective study A. Ighani, J.R. Georgakopoulos, N.H. Shear, S. Walsh and J. Yeung
P – 57 A comparison of apremilast monotherapy and combination therapy for plaque psoriasis in clinical practice: a multicentre retrospective study A. Ighani, J.R. Georgakopoulos, S. Walsh, N.H. Shear and J. Yeung
P – 58 An evaluation of the quality of life, treatments and resources available for patients with psoriasis in Canada: a comparison of biologic and nonbiologic users A. Ighani and M.F. Manolson
P – 59 Identification of promising biomarkers to predict therapeutic response to biologics in psoriasis A. Medeiros, L. Grine, M. Van Gele, P. Spuls and J. Lambert
P – 60 Evaluation of carcinogenic risk of psoralen,ultraviolet A (PUVA) vs. retinoid,PUVA in patients with psoriasis H. Mashaly, M. Fathy, S. Hamdy and O. Shaker
P – 61 Successful treatment of recalcitrant hyperkeratotic palmoplantar psoriasis with itolizumab: a case series of three patients U. Chakravadhanula and B.K. Jha
P – 62 Systemic therapy and the risk of nonmelanoma skin cancer among patients in the Psoriasis Longitudinal Assessment and Registry R. DeShazo, R. Soltani-Arabshahi, S. Krishnasamy, C. Galindo, W. Langholff, R. Langley, S. Kalia, S. Fakharzadeh, K. Goyal, M. Ståhle, B. Srivastava and G.G. Krueger
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P – 63 Interleukin-10 regulates skin thickness and scaling in imiquimod-induced psoriasis-like skin inflammation in mice X. Xu, E. Prens, E. Florencia, L. Boon, P. Asmawidjaja, A.-M. Otten-Mus and E. Lubberts
P – 64 The identification of interleukin (IL)-17A+, IL-17RA+ and IL-17RC+ lymphoid and myeloid cells in blood of treatment-naive early patients and in synovial fluid of established patients with psoriatic arthritis X. Xu, N. Davelaar, A.-M. Otten-Mus, P. Asmawidjaja, H. den Braanker, J. Hazes, R. Bisoendial, M. Vis and E. Lubberts
P – 65 Distinct and overlapping activities of interleukin (IL)-17A and tumour necrosis factor (TNF) on the expression of proinflammatory cytokines and matric metalloproteinases in psoriatic arthritis: rationale for anti-IL-17A/anti-TNF-α combination therapy? X. Xu, N. Davelaar, A.-M. Otten-Mus, P. Asmawidjaja, J. Hazes, D. Baeten, M. Vis, R. Bisoendial and E. Lubberts
P – 66 Unopposed interleukin (IL)-36 activity promotes clonal CD4+ T-cell responses with IL-17A production in generalized pustular psoriasis A. Arakawa, S. Vollmer, P. Besgen, B. Summer, P. Thomas, T. Ruzicka and J.C. Prinz
P – 67 Remarkable response of recalcitrant hyperkeratotic palmoplantar psoriasis to itolizumab: a case report U. Chakravadhanula and B.K. Jha
P – 68 Effects of methotrexate on treatment and serum inflammatory cytokines in paediatric patients with severe plaque psoriasis Z. Xu, Y. Gu and Z. Wang
P – 69 Sustained remission in a patient with chronic plaque psoriasis treated with itolizumab: a 4-year follow-up experience S.G. Parasramani, G.G. Kunder, S.H. Suresh and D.R. Pawar
P – 70 Treat to target in psoriasis: a Belgian attempt to define a tight control strategy for psoriasis management L. Grine, S. Segaert, J. Lambert, M. de la Brassinne, P.-D. Ghislain, F. Willaert, T. Hillary and J. Lambert
P – 71 Retrospective review of psoriasis ustekinumab outcomes using real clinic data analysed using starting Psoriasis Area and Severity Index (PASI) and worst PASI in the preceding 5 years with PASI 75 and 90 reported C. Goodhead and P. Hampton
POSTER PRESENTATIONS CONTINUED
P – 72 Role of keratin 24 in human epidermal keratinocytes M. Min, X.-B. Chen, P. Wang, L. Landeck, J.-Q. Chen, W. Li, S. Cai, M. Zheng and X.-Y. Man
P – 73 Deletion of PCSK9 can suppress psoriasis-like inflammation in an animal model M. Chen, R. Yuan, C. Luan, X. Chen, J.M. Osland, S.J. Gerber, M. Dodds and Y. Hu
P – 74 Correlation between Dermatology Life Quality Index and Psoriasis Area and Severity Index in patients with psoriasis treated with ustekinumab J.H. Hesselvig, A. Egeberg, N.D. Loft, C. Zachariae, K. Kofoed and L. Skov
P – 75 Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis A. Egeberg, M.B. Ottosen, R. Gniadecki, S. Broesby-Olsen, T. Dam, L.E. Bryld, M.K. Rasmussen and L. Skov
P – 76 Predictive factors of pruritus among patients with psoriasis C. Ebongo, S. Mansouri and B. Hassam
P – 77 Education of patients with psoriasis C. Ebongo, S. Mai, M. Meziane and B. Hassam
P – 78 Psychiatric comorbidity, psychotropic medication prescribing and suicidality in patients with psoriasis: a population-based cohort study R. Parisi, R.T. Webb, C.E. Kleyn, M.J. Carr, N. Kapur, C.E.M. Griffiths and D.M. Ashcroft
P - 79 Dithranol in psoriasis: keratinocyte–neutrophil cross-talk as the early target T.H. Benezeder, C. Painsi, G. Mayer, U. Schmidbauer, K. Hammer, B. Lange-Asschenfeld and P. Wolf
P - 80 Effectiveness and safety of off-label secukinumab dosing regimens for the treatment of moderate-to-severe plaque psoriasis in adult patients: a retrospective multicentre study M. Phung, J.R. Georgakopoulos, A. Ighani and J. Yeung
P – 81 Comorbidities in patients with psoriasis according to Charlson Comorbidity Index: 6 years of experience in Bogotá, Colombia C. Cortes, E. Peñaranda, D. Chaparro, L. Peña and E. Roa
P – 82 Relationship between age of onset, male-to-female ratio and family history of Japanese patients with psoriasis: comparison with other East Asian countries B. Bayaraa and S. Imafuku
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P – 83 The journey of adult patients with psoriasis towards biologics past and present: results from the BioCAPTURE registry J. van den Reek, M. Seyger, P. van Lüimig, R. Driessen, L. Schalkwijk, M. Berends, P. van de Kerkhof and E. de Jong
P – 84 Skin mast cells: critical drivers of psoriasis? M.J. Barron, C.E.M. Griffiths and S. Bulfone-Paus
P - 85 Secukinumab demonstrates high sustained efficacy and a favourable safety profile through 5 years of treatment in moderate-to-severe psoriasis R. Bissonnette, T. Luger, D. Thaçi, D. Toth, A. Lacombe, S. Xia, R. Mazur, P. Manmath, C. Pascal, M. Milutinovic and C. Leonardi
P – 86 Infliximab is associated with an increased risk of serious infection in patients with psoriasis: results from the British Association of Dermatologists Biologic Interventions Register (BADBIR) Z. Yiu, C. Smith, D. Ashcroft, M. Lunt, S. Walton, R. Murphy, N. Reynolds, A. Ormerod, C.E.M. Griffiths and R.B. Warren
P- 87 Efficacy and tolerance assessment of an anti-itching spray in patients with psoriasis S. Virassamynaik, B. Chadoutaud, C. Eydieux, J. Riviere and M. Sayag
P – 88 Gene expression and protein changes from blood and skin correlate with disease improvement in patients with psoriasis treated with PF06700841, a tyrosine kinase2/ Janus kinase 1 inhibitor L. Xi, E. Kieras, M. Suarez-Farinas, B. Zhang, K. Page, J. Lee, S. Du, L. Fitz, W. Gordon, W. Zhang, J. Krueger and E. Peeva
P - 89 Interleukin (IL)-36γ induces IL-23 production and angiogenesis in psoriasis C. Bridgewood, G. Fearnley, A. Keszegpal, P. Laws, S. Ponnambalam, A. Graham, M. Stacey and M. Wittmann
P – 90 One-year pilot study to evaluate sequential therapy with ciclosporin and itolizumab in treatment of chronic plaque psoriasis U. Chakravadhanula, B.S. Chandrashekar, M. Parekh, D.S. Krupashankar, H.S. Swaroop and D. Pawar
P - 91 Examining the impact of treatment by a dermatologist vs. nondermatologist in psoriasis care M. Porter, N. Golbari, S. Lockwood and A. Kimball
POSTER PRESENTATIONS CONTINUED
P – 92 Ixekizumab maintains reductions in Psoriasis Area and Severity Index through the third year of treatment: results from the UNCOVER-3 extension study P. Fernández-Peñas, O. Goldblum, L. Berggren, N. Burkhardt and L. Puig
P – 93 Starting biologic treatment sequences for plaque psoriasis with ustekinumab or adalimumab is the most cost-effective: a costutility analysis based on 10 years of Dutch real-world evidence from BioCAPTURE S. Klijn, J. van den Reek, G. van de Wetering, A. van der Kolk, E. de Jong and W. Kievit
P – 94 52-Week results from IXORA-S: a randomized head-to-head trial of ixekizumab and ustekinumab in patients with moderate-to-severe plaque psoriasis C. Paul, P. van de Kerkhof, Y. Dutronc, C. Henneges, M. Dossenbach, K. Hollister and K. Reich
P – 95 The genotype of susceptibility genes in psoriasis predicting the response and hepatotoxicity to methotrexate treatment J. Xu, X. Zhang and K. Yan
P – 96 Evaluation of the efficacy of granulocyte and monocyte adsorption apheresis on skin manifestation and joint symptoms of patients with pustulotic arthro-osteitis H. Kawakami, N. Abe, Y. Matsumoto, H. Hirano, R. Tsuboi and Y. Okubo
P – 97 Multicomponent biomarkers: a novel method for accurate diagnosis of psoriasis F. Lättekivi, E. Reimann, M. Keermann, K. Abram, S. Kõks, K. Kingo and A. Fazeli
P – 98 Genome-wide DNA methylation profiling identifies differential methylation in uninvolved psoriatic epidermis D. Verma, A.-K. Ekman, C.B. Eding and C. Enerbäck
P – 99 Gene expression changes induced by individual interleukin (IL)-17 family cytokines signalling through IL-17RA D.A. Ewald, P. Lovato, T. Skak-Nielsen and H. Norsgaard
P – 100 Validity of self-reported psoriasis in a Danish birth cohort C. Blegvad, T.E.T. Nielsen, C. Zachariae, A.-M.N. Andersen and L. Skov
P – 101 Intentional and unintentional medication nonadherence in psoriasis: the role of patients’ medication beliefs and habit strength R. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft and L. Cordingley; on behalf of the PSORT study group and BADBIR
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P – 102 Prognostic effect of psoriasis and psoriatic arthritis in patients with suspected coronary artery disease assessed by cardiac computed tomography: a multicentre cohort study K.F. Hjuler, S. Winther, M. Bøttcher and L. Iversen
P – 103 Safety of guselkumab in patients with plaque psoriasis through 2 years: a pooled analysis from VOYAGE 1 and VOYAGE 2 K. Reich, K. Papp, A.W. Armstrong, Y. Wasfi, G. Jiang, Y.-K. Shen, B. Randazzo, M. Song and A.B. Kimball
P – 104 Additional efficacy benefit of continuous ixekizumab every-2-week dosing among patients with psoriasis who do not respond by week 12 K. Papp, M. Gooderham, P. Polzer, L. Zhang and M. Augustin
P – 105 Absolute Psoriasis Area and Severity Index improvement through 2 years of guselkumab treatment in the VOYAGE 1 trial of patients with plaque psoriasis K. Papp, C.E.M. Griffiths, A.B. Kimball, S. Li, Y.-K. Shen, Y. Wasfi and A. Blauvelt
P – 106 Guselkumab treatment results in more effective and durable inhibition of T helper (Th)17 and Th22 cells and downstream effectors compared with adalimumab X. Liu, P.J. Branigan, Y. Chen, S. DePrimo, K. Campbell and E.J. Munoz
P – 107 Cost of topical therapies for patients with psoriasis in Georgia K. Tsagareishvili and N. Chijavadze
P – 108 Looking beyond 12 weeks: long-term drug survival and safety of secukinumab in real-world patients with plaque psoriasis J.R. Georgakopoulos, A. Ighani, M. Phung and J. Yeung
P – 109 Efficacy and safety of ixekizumab in secukinumab nonresponders: therapeutic options for nonanti-interleukin-17A-naive patients J.R. Georgakopoulos, M. Phung, A. Ighani and J. Yeung
P – 110 Long-term, real-world efficacy of infliximab for psoriasis L. Mercieca, R.B. Warren and C.E.M. Griffiths
P – 111 Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis in a Chinese population X. Fan, H. Wang, L. Sun, X. Yin, X. Zuo, Q. Peng, K. A. Standish, X. Zheng, Z. Wang, F. Xiao, S. Yang, X. Zhang and N.J. Schork
P – 112 Retrospective study of childhood psoriasis M.S. Zorko and O. Tockova
POSTER PRESENTATIONS CONTINUED
P – 113 Immature progenitor cells are enriched in psoriasis epidermis A.-K. Ekman, C.B. Eding, I. Rundquist and C. Enerbäck
P – 114 PRINS long noncoding RNA regulates the expression of interleukin-6 and CCL-5 by direct interaction J. Danis, A. Göblös, L. Janovák, Z. Bata-Csörgő, L. Kemény and M. Széll
P – 115 CARD14 variants in pityriasis rubra pilaris A. Göblös, J. Danis, B. Gál, K. Farkas, E. Varga, I. Korom, L. Kemény, N. Nagy, M. Széll and Z. Bata-Csörgő
P – 116 Early changes in peripheral leucocyte populations during oral dimethylfumarate treatment P. Morrison, D. Stölzl, S. Kurras, S. Gerdes and U. Mrowietz
P – 117 Randomized controlled trial of patient-initiated care for patients with psoriasis L. Khoury, T. Møller, C. Zachariae and L. Skov
P – 118 Establishment of an intradermal ear injection model of interleukin (IL)-17A and IL-36γ as a tool to investigate the psoriatic cytokine D. Kluwig, S. Huth, C. Pfaff, L. Huth, Y. Marquardt, K. Fietkau, J.M. Baron and B. Lüscher
P – 119 Pharmacogenomic signature of response to genistein therapy for psoriasis: effects of genistein in vitro and in vivo and its mechanism of action E. Smolińska, M. Moskot, K. Bocheńska, A. Lewczuk, T. Brodniewicz, J. Jakóbkiewicz-Banecka and M. Gabig-Cimińska
P - 120 Itch and pain perception and epidemiology in patients with psoriasis: results from a prospective two-centre study N. Max, K. Torz, U. Mrowietz, V. Oji, S. Ständer and S. Gerdes
P – 121 Body locations of difficult-to-treat psoriasis in the era of treatment with biological agents: a Danish multicentre study K.F. Hjuler, L. Iversen, K. Kofoed, M. Rasmussen, L. Skov and C. Zachariae
P – 122 The effect of monomethylfumarate on human blood neutrophils I. Suhrkamp, A.-S. Erkens, P. Morrison and U. Mrowietz
P – 123 Psychological distress in patients using systemic therapies for psoriasis: the role of beliefs about illness and anger suppression R. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft and L. Cordingley; on behalf of the PSORT study group and BADBIR
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INDUCTION AND REGULATION OF TH17 CELLS
PROFESSOR VIJAY KUCHROOBoston, USA
Dr. Vijay Kuchroo is the Samuel L. Wasserstrom Professor of Neurology at Harvard Medical School, Senior Scientist at Brigham and Women’s Hospital, and Co-Director of the Center for Infection and Immunity, Brigham Research Institutes, Boston. Vijay Kuchroo is also an associate member of the Broad Institute and a participant in a Klarman Cell Observatory project that focuses on T cell differentiation. He was just named the Director of the newly formed Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women’s Hospital. His major research interests include autoimmune diseases - particularly the role of co-stimulation - the genetic basis of experimental autoimmune encephalomyelitis and multiple sclerosis, and cell surface molecules and regulatory factors that regulate induction of T cell tolerance and dysfunction. His laboratory has made several transgenic mice that serve as animal models for human multiple sclerosis. Dr. Kuchroo first described the inhibitory receptor TIM-3, which is being exploited as a target for cancer immunotherapy. He was first to describe the development of highly pathogenic Th17 cells, which has been shown to induce multiple different autoimmune diseases in humans. He has published over 325 original research papers in the filed of Immunology and a paper describing development of Th17 authored by Dr. Kuchroo has been one of the highest cited papers in Immunology.
Dr. Kuchroo came to the United States in 1985 and was at the National Institutes of Health, Bethesda as Fogarty International Fellow for a year before joining the department of pathology at Harvard Medical School as a research fellow. He later joined the Center for Neurologic Diseases at Brigham and Women’s Hospital as a faculty member in 1992.
He obtained his degree in Veterinary Medicine from the College of veterinary medicine, Hisar, India. Subsequently, he specialized in pathology at the University of Queensland, Brisbane (Australia) where he obtained a Ph.D. in 1985. He received the Fred Z. Eager Research prize and medal for his Ph.D. research work at the University of Queensland. Based on his contributions, he was awarded the Javits Neuroscience Award by the National Institutes of Health in 2002 and the Ranbaxy prize in Medical Research from the Ranbaxy Science Foundation in 2011. He was named Distinguished Eberly lecturer in 2014 and obtained Nobel Laureate Peter Doherty lecture/prize in 2014.
Dr. Kuchroo has 25 patents and has founded 6 different biotech companies. He also serves on the scientific advisory boards of a number of big pharmaceutical companies including Pfizer, Novartis, Sanofi/Genzyme and Glaxo-Smith-Klein (GSK).
SPEAKER BIOGRAPHIES
ABSTRACT
IL-17 producing Th17 cells are distinct from TH1 or TH2 cells and have been shown to play a crucial role in the induction of multiple human autoimmune diseases including psoriasis, psoriatic arthritis, ankylosing spondylitis and multiple sclerosis. Th17 differentiation is accomplished by three overlapping steps: Induction, Amplification and Stabilization mediated by distinct cytokines. Whereas TGF-b+ IL-6 or IL-1 + IL-6 induces them, IL-21 amplifies Th17 cells, IL-23 stabilizes the phenotype of Th17 cells. Loss of any of the cytokines (TGF-β, IL-1, IL-6, IL-21 or IL-23) in the pathway results in a defect in generation of Th17. However not all Th17 cells are pathogenic and induce autoimmunity, IL-23 is a key cytokine that induces pathogenicity in Th17 cells (Lee et al., 2012). Using expression profiling at very high temporal resolution, novel computational algorithms and innovative nano-wire based “knock-down” approaches, we have developed a regulatory network that governs the development of Th17 cells. In addition to high-density temporal microarray analysis, we have performed single-cell RNA-seq of Th17 cells in order to characterize cellular heterogeneity, identify subpopulations, functional states and learn how gene expression variation affects Th17 functional states. We have identified novel regulators of Th17 cells both in vivo and in vitro that do not affect Th17 differentiation but affects pathogenic vs. non-pathogenic functional states of Th17 cells. One of the regulators CD5L (CD5like) has both cell intrinsic and cell extrinsic effects. Soluble forms of CD5L makes homo and heterodimers and regulates differentiation of Th17 cells and inhibit development of tissue inflammation and autoimmunity.
NOTES
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THE HUMAN SKIN MICROBIOME AND IMPLICATIONS FOR DISEASE
PROFESSOR BJORN ANDERSSONStockholm, Sweden
Björn Andersson received his PhD in 1992 and was a post-doctoral fellow at Baylor College of Medicine 1992-1995. He is now, after working as an assistant and associate professor at Uppsala University and Karolinska Institutet, a professor at the Department of Cell and Molecular Biology, Karolinska Institutet since 2007. With a background in human genetics and the human genome project, his own laboratory has focused on the study of human pathogens using genomics and bioinformatics methods. He has, for example, pioneered studies on protozoan genomes by leading the Trypanosoma cruzi genome project and viral microbiome projects (published in Science 2005, PNAS 2005, J. Virol. 2007), as well as participated in a large skin microbiome study.
ABSTRACT
The involvement of the human microbiome in disease is currently a rapidly developing field. The skin microbiome has been characterized in smaller sample sets and mainly in healthy individuals, in order to understand microbial diversity in skin homeostasis, but the relevance of microbial dysbiosis in inflammatory disease is still relatively unexplored. We have carried out the microbiome part of a large European study of the development of allergic and autoimmune skin disease, in this case atopic dermatitis and psoriasis. We have deeply sequenced skin microbial communities both by 16S sequencing and shotgun sequencing, and coupled this with transcriptome data of cutaneous gene expression in skin biopsies from the to date largest patient cohort characterized to date. The analysis of the 16S data showed that the microbiome signatures of atopic dermatitis and psoriasis samples showed clear differences from those of healthy volunteers. We were able to associate the microbiome with changes in gene expression for both diseases and identify inflammatory pathways of interest. The shotgun data has been analyzed and has deepened the analysis to include specific genes and strains as well as fungi and viruses. The analysis is still ongoing and the latest results will be discussed. These data sets provide information that can lead to the development of new biomarkers as well as new insight into factors important for skin diseases and symptoms.
SPEAKER BIOGRAPHIES
THE IMPORTANCE OF ACADEMIC-INDUSTRIAL COLLABORATION TO THE FUTURE OF MEDICAL RESEARCH
PROFESSOR SIR JOHN SAVILLLondon, UK
Professor Sir John Savill BA, MBChB, PhD, FRCP, FRCPE, FASN, FMedSci, FRS, FRSE, a clinician scientist from Edinburgh, took up the position as chief executive and deputy chair of the Medical Research Council on 1 October 2010. The appointment was initially for three years; after which it was extended until April 2016, and subsequently to 30 September 2018. He was a member of the Council from 2002 to 2008 and chaired two Research Boards during this period.
Between 2008 and 2010 John worked part-time as the chief scientist for the Scottish Government Health Directorates.
He was knighted in the 2008 New Year Honours List for services to clinical science.
John started his research career with a degree in Physiological Sciences from Oxford University in 1978, followed by degrees in Medicine at the University of Sheffield in 1981. He received a PhD from the University of London in 1989.
After junior hospital appointments in Sheffield, Nottingham and London, he spent seven years in the Department of Medicine at Hammersmith Hospital with spells as an MRC clinical training fellow and Wellcome Trust senior clinical research fellow.
In 1993, he moved to the chair of medicine, at the University of Nottingham, then in 1998 became professor of medicine at the University of Edinburgh, where he was the first director of the University of Edinburgh/MRC Centre for Inflammation Research, directing a group interested in the molecular cell biology of renal inflammation.
In 2002, John was appointed as the first vice-principal and head of the College of Medicine and Veterinary Medicine, University of Edinburgh. He retains an ongoing, research active involvement with the University of Edinburgh part time throughout his appointment as our chief executive.
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LILLY SPONSORED LECTURE
TARGETING IL-17: FINDINGS FROM RECENT CLINICAL TRIALS.
DR ANDREW BLAUVELTPortland, USA
Andrew Blauvelt hails from Portland, OR, USA, and is President and Investigator at Oregon Medical Research Center – a small company dedicated to conducting high-quality clinical studies in dermatology. A native of Michigan, Dr. Blauvelt received degrees in Electrical Engineering at Purdue University (West Lafayette, IN), and Medicine at Michigan State University (East Lansing, MI), before completing his MBA at Portland State University/Oregon Health & Science University (OHSU, Portland, OR). Dr. Blauvelt trained in dermatology at the University of Miami from 1989–1992 and in basic immunology and virology in Dr. Steve Katz’s laboratory at the National Institutes of Health (NIH) from 1992–1996. He has held senior staff positions at the NIH and more recently was Professor of Dermatology and Microbiology at OHSU and Chief of Dermatology at the Portland VA Medical Center.
Dr. Blauvelt’s clinical and research expertise spans immunology, virology, infectious diseases, psoriasis, atopic dermatitis, and biologic therapies for complex medical dermatology patients. He has published more than 200 papers and spoken globally on these topics. Dr. Blauvelt is an elected member of both the American Society for Clinical Investigation, a leading society for physician-scientists; and the International Psoriasis Council, a premier group of psoriasis experts worldwide. More recently, he has participated extensively in clinical trials assessing biologic therapies for atopic dermatitis, and has served as a lead scientific advisor for companies working in this area.
ABSTRACT
This will be an overview of recent Lilly clinical trial data. This presentation has been organised and funded by Lilly and Lilly products will be discussed in this session.
SPEAKER BIOGRAPHIES
NOTES
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ALMIRALL SPONSORED LECTURE
THE EPIDEMIOLOGY AND INTERRELATION OF PSORIASIS AND OTHER IL-23 RELATED DISEASES
PROFESSOR ALEXA KIMBALLBoston, USA
Alexa Boer Kimball, MD, MPH is President and Chief Executive Officer of Harvard Medical Faculty Physicians at BIDMC, Inc., an academic multi-specialty group practice with over 1200 Harvard Medical School faculty members at Beth Israel Deaconess Medical Center in Boston, Massachusetts and an additional 400 physicians based in the community . She is also President of the Beth Israel Deaconess Care Organization (BIDCO) Physician LLC which maintains a membership of approximately 2500 physicians. A Professor of Dermatology at Harvard Medical School, Dr. Kimball’s areas of research include psoriasis and hidradenitis suppurativa. She has published over 275 papers, is the author of the book “100 Questions and Answers about Psoriasis,” which has been translated into Spanish, Greek, and Korean, and editor of “Dermatologic Diseases and Cumulative Life Course Impairment.” Dr. Kimball is widely recognized for her research on physician workforce economics, quality of life, and outcomes, for which she was awarded the American Skin Association Research Award for Health Policy and Medical Education and the Mass General Hospital Bowditch Prize for increasing quality of care while reducing costs. Dr. Kimball has served on multiple non-profit Boards including: the Society for Investigative Dermatology, where she was elected Vice President, the Massachusetts Foundation for the Humanities and Public Policy, and the Hidradenitis Suppurativa Foundation. She was previously Senior Vice President of the Massachusetts General Physician Organization, which employs more than 2500 physicians, and also served as Medical Director (chief medical officer) of this organization. She is current President of the International Psoriasis Council.
ABSTRACT
The elucidation of the role of IL-23 in psoriasis and other diseases has been a fascinating story of concurrent and synergistic discovery driven by laboratory findings, translational investigation, clinical observation, and epidemiology. As has often been in the case in dermatology, clinical observation drove some of the early hypotheses. The clinical and laboratory observations that p40 inhibitors that affected both IL12 and a relatively newly recognized cytokine in a novel pathway led to clarifications that ultimately revealed the TH-17 pathway and the pivotal role of IL23. Comorbid conditions in patients with psoriasis were being described in depth in parallel and soon thereafter, genetic epidemiology confirmed a biologic basis for these relationships. Yet there appear to be interesting biologic differences between the effects across these related comorbid but disparate diseases which will be discussed. Our understanding of these differences and the fundamental biology will only improve as we observe the effects of new agents that target the p19 moiety of IL-23 and therefore are expected to have even more targeted effects in clinical practice.
SPEAKER BIOGRAPHIES
LEO PHARMA SPONSORED LECTURE
PRO-INFLAMMATORY REDUNDANCY IN THE IL-17 PATHWAY - THE ROLE OF THE INDIVIDUAL IL-17 CYTOKINE FAMILY MEMBERS IN PSORIASIS
PROFESSOR JAMES KRUEGERNew York, USA
James G, Krueger, MD, PhD is Head of the Laboratory for Investigative Dermatology at the Rockefeller University. He also serves as a Physician, Co-director, Center for Clinical and Translational Science at the Rockefeller University Hospital, and Chief Executive Officer of the Rockefeller University Hospital in New York City.
Dr.Krueger earned his bachelor’s degree from Princeton University and a PhD in virology and cell biology from the Rockefeller University. He received an MD from Cornell University Medical College, where he also completed an internship in internal medicine and residency in dermatology. Dr.Krueger is certified by the American Board of Dermatology.
His research group at Rockefeller was the first to conduct clinical trials with specific, targeted immune antagonists in psoriasis and this work established that elimination of pathogenic T-cells from skin lesions could reverse the full pathological phenotype of psoriasis. Since then his group has used immune-based therapeutics to dissect inflammatory pathways in psoriasis and to conduct parallel pharmacogenomic studies that define mechanisms of targeted therapeutics in human populations. A more recent focus has been definition of new inflammatory pathways, as well as new types of inflammatory cells in psoriasis lesions that are now being targeted with new biologic drugs. He has been an advocate of bidirectional translational research (bench to bedside and back) in humans using psoriasis as a model inflammatory disease to dissect pathogenic pathways that cannot be studied in animal models.
ABSTRACT
The interleukin-17 (IL-17) pathway is central in the pathophysiology of psoriasis as evidenced by the high levels of skin clearance achieved by therapies that directly target the IL-17 cytokine or it’s receptor. Increased expression of IL-17 cytokines, which signal through the IL-17 receptor complex directly on the surface of keratinocytes and immune cells, leads to release of pro-inflammatory mediators, resulting in inflammation and clinical manifestations of psoriasis. IL-17 is not a single cytokine, but comprises a family of 6 pro-inflammatory cytokine members: IL-17A to IL-17F. IL-17A, IL-17C, IL-17E, IL-17F and the IL-17A/F heterodimer have all been described to have a role in psoriasis.
This lecture will review the current understanding of each IL-17 family member and their role in psoriasis, presenting new transcriptomics data, and linking it to a better understanding of the pro-inflammatory redundancy in the IL-17 pathway.
PSORIASISfrom gene to clinic
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JANSSEN SPONSORED LECTURE
IL-23 INHIBITION AS A STRATEGY TO TREAT IMMUNE-MEDIATED INFLAMMATORY DISEASES
PROFESSOR JÖRG PRINZMunich, Germany
Jörg Prinz is Professor of Dermatology and Venereology at the Clinic for Dermatology and Allergology of the Ludwig-Maximilian University (LMU) in Munich, Germany. He graduated with a medical degree in 1983. After 5 years of basic immunology research as a postdoctoral fellow, he joined the Clinic for Dermatology and Allergology in 1990, where he founded the Research Group for Immunopathology. Professor Prinz earned specialist qualifications in dermatology and venerology in 1995 and in allergology in 1996, and was appointed as Full Professor of Dermatology in 2001. His current responsibilities include being deputy chair of the department and supervising the phototherapy unit and psoriasis centre, and the serological analysis laboratory. At medical school he received several rewards for his commitment to education.
Professor Prinz’s main research interest is in the analysis of the T-cell mediated immunopathogenesis of psoriasis and the identification of psoriatic autoantigens; he is also interested in developing experimental therapies for T-cell mediated autoimmune disorders, and has been actively involved in preparing evidence-based guidelines for psoriasis treatment. He has published extensively in major peer-reviewed journals.
Professor Prinz is a member of the European Academy of Dermatology and Venereology, the International Psoriasis Council, and the International Federation of Psoriasis Associations. He was the Scientific Chairman of the 2nd World Psoriasis and Psoriatic Arthritis Conference in Stockholm, Sweden, in 2009.
PROFESSOR SILVIO DANESEMilan, Italy
Silvio Danese is Head of the Inflammatory Bowel Disease (IBD) Center, Division of Gastroenterology, at Humanitas Research Hospital and Professor in Gastroenterology at Humanitas University, both in Milan, Italy. He trained in gastroenterology at Policlinico Gemelli, Rome, Italy, and earned his PhD there in 2004. Professor Danese also worked in Prof. Claudio Fiocchi’s laboratory at the Case Western Reserve University, Cleveland, OH, USA from 2001 to 2004.
His main research area of interest is the investigation of the fundamental mechanisms underlying IBD pathogenesis, while his daily clinical activity is related to IBD service. He is actively involved in many international clinical trials in IBD-related areas and has published more than 300 papers in peer-reviewed journals, including Gastroenterology, Gut, Journal of Clinical Investigation, Nature, and Journal of Immunology.
SPEAKER BIOGRAPHIES
Professor Danese is a member of many organizations related to the IBD field, including the European Crohn’s and Colitis Organisation (ECCO), where he served as Secretary from 2012 to 2015 and as President-elect from March 2016 to present. He is also Scientific Secretary for the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) and sits on the Editorial Board of Gut and Alimentary Pharmacology & Therapeutics.
ABSTRACT
The recent introduction of novel treatments targeting the IL-23/Th17 immune pathway has had major implications for our management of patients with moderate-to-severe plaque psoriasis, and potentially for management of patients with other immune-mediated inflammatory diseases (IMIDs) such as inflammatory bowel disease (IBD). Patients suffering from moderate-to-severe psoriasis now have additional treatment options that have been shown to significantly improve skin clearance and reduce the debilitating symptoms such as itch, pain, stinging, burning, and skin-tightness.
In our presentations, we will show how the effectiveness of IL-23 inhibition in treating IMIDs is based on a thorough understanding of the role of IL-23 in disease pathogenesis. Clinicians have been able to formulate effective management strategies for day-to-day clinical practice based on an understanding both of this role and of how the different IL-23 inhibitors act and where they have effect.
Our presentation will include: • The IL-23/Th17 immune pathway in psoriasis and other IMIDs: activation, differentiation, and amplification,
and the implications for patient treatment • A review of the latest clinical data on IL-23-specific inhibitors • Practical lessons learned from the use of these agents in day-to-day clinical practice
We will also address unmet medical needs in the management of IMIDs, and demonstrate how these needs can be met by IL-23 inhibition. Importantly, and uniquely, we will also offer insights from both the dermatological and gastroenterological perspectives, highlighting the benefits of a cross-specialty approach in managing IMIDs.
PSORIASISfrom gene to clinic
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FROM GWAS TO SYSTEMATIC HOST-MICROBIOME ASSOCIATION STUDIES IN COMPLEX IMMUNE-MEDIATED DISEASES
PROFESSOR ANDRE FRANKEKiel, Germany
Professor Franke’s main scientific interests are the development and establishment of novel high-throughput technologies, the inherent bioinformatic integration and application of both to identify genetic and epigenetic causes of chronic inflammatory diseases such as Crohn’s disease, ulcerative colitis, psoriasis, primary sclerosing cholangitis, and atopic eczema. Having worked on genome-wide association studies for the last years, his research agenda currently focuses on clinical data management, whole-genome and whole-exome resequencing, microbiome analyses and immunogenetics studies.
ABSTRACT
Genome-wide association (GWAS) have significantly contributed to our understanding of the etiology of chronic and complex immune-mediated diseases (CID). Inflammatory bowel diseases (IBD) with its main sub phenotypes Crohn’s disease and ulcerative colitis, are prototypic CIDs that affect about 2-3 persons out of a 1000 in Western countries. IBD shares part of its genetic and immunological background with diseases like psoriasis, ankylosing spondylitis, and primary sclerosis cholangitis. To this end, over 250 genetic susceptibility loci were identified in the past 10 years through GWAS and candidate-gene association studies. Complex immunogenetics efforts are currently being undertaken to solve CID. Still, the exact cause of most CID has not been identified and components of the gut microbiome are also likely disease-causing environmental factors for CID. In my talk I will focus on our ongoing efforts in host-microbiome association analyses and allude to the methodological challenges of these kind of analyses. I will show immunogenetics and host-microbiome interaction approaches, which could serve as a role model for psoriasis research projects.
SPEAKER BIOGRAPHIES
FROM GENOME WIDE ASSOCIATION TO FUNCTIONAL RELEVANCE
DR TUULI LAPPALAINENNew York, USA
Tuuli Lappalainen is an Assistant Investigator and Core Member at the New York Genome Center, and an Assistant Professor in the Department of Systems Biology at Columbia University. She got her PhD from University of Helsinki in 2009, and did postdoctoral research with Manolis Dermitzakis at University of Geneva, and Carlos Bustamante at Stanford University. Her research focuses on functional genetic variation in human populations and its contribution to traits and diseases. She has pioneered in integration of large-scale genome, transcriptome and epigenetic data to learn how genetic variation affects gene regulation – the largely unknown factor that underlies the majority of human diversity and disease risk. Her research group tackles these questions by both computational analysis of large data sets and experimental work using genome editing assays. She has contributed to several international research consortia in human genomics, including the 1000 Genomes Project, the Geuvadis project, and the Genotype Tissue Expression (GTEx) Project.
ABSTRACT
Detailed characterization of cellular effects of genetic variants is essential for understanding biological processes that underlie genetic associations to disease, as well as basic genome function. One approach to address this challenge is map genetic effects on the transcriptome across multiple human tissues and conditions. In this talk, I will discuss our recent work in integrating large-scale data sets of genome and transcriptome variation to understanding genetic regulatory variants, genetic effects on transcriptional response to immune stimuli, and their contribution to autoimmune and other diseases.
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
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WHY BIOLOGICS FAIL
PROFESSOR ANN GILSLeuven, Belgium
As a pharmacist, Ann Gils obtained her PhD in Pharmaceutical Sciences in 1997. She is a full professor at the Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium. The core technology of the laboratory is the development of monoclonal antibodies and antibody fragments with the aim to develop these antibodies either as therapeutics or as diagnostics.
In the past few years, she has developed and validated a number of assays to measure the serum and anti-drug antibody concentrations of biologicals (infliximab; adalimumab; etanercept, golimumab, vedolizumab, secukinumab and ustekinumab) and has participated in Therapeutic Drug Monitoring studies in the field of gastroenterology, rheumatology and dermatology. Through PKPD modeling, she studies the effect of co-variates on PK and PD. She has published more than 200 papers in the field of thrombosis and therapeutic drug monitoring of biologicals.
ABSTRACT
Chronic inflammatory diseases such as rheumatic diseases, spondyloarthritis, inflammatory bowel diseases and plaque psoriasis have a high prevalence and typically start early in life, thereby strongly affecting the quality of life and productivity of young and active individuals. Patients have to be treated life-long and this requires safe, tolerable and cost-effective treatments. The introduction of biologics has revolutionized the short- and long-term outcome of patients with chronic inflammatory diseases. Unfortunately, 10-30% of patients (primary non-response) will not respond to treatment and 30-60% of patients initially responding will lose clinical benefit during treatment (secondary loss of treatment). Primary non-response is defined as a lack of clinical response to the treatment, assessed 8-12 weeks after initiation. It is believed that this primary non-response is mainly driven through mechanistic override of the disease. Another explanation is that primary non-response is caused by non-sufficient exposure to the drug. A drug can only exert its pharmacological effect when adequate concentrations of drug are achieved in the circulation and at the drug’s site of action. Inter-and intra-individual differences in bioavailability and pharmacokinetics may contribute to the problem of insufficient exposure. Secondary loss of response is defined as a loss of clinical benefit after initially responding to the drug. The secondary loss of response can either be attributed to disease-related factors or drug-related factors such as the formation of anti-drug antibodies.
SPEAKER BIOGRAPHIES
In inflammatory bowel diseases and rheumatoide arthritis patients, it has recently been shown that adequate serum concentrations of biologics are associated with sustainable clinical response. Pharmacological guidance using drug concentrations of biologics is emerging in European countries as a valuable tool for clinical decision making and growing evidence suggests that monitoring drug concentrations and anti-drug antibody concentrations together with clinical response also allows a better management of patients with plaque psoriasis. A growing body of evidence demonstrates an exposure-response association for psoriasis patients treated with infliximab, adalimumab and to some extent for ustekinumab. For etanercept, an age-dependent association between exposure and psoriasis severity was recently reported.
NOTES
PSORIASISfrom gene to clinic
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BIOLOGY AND PATHOLOGY OF IL-36
DR JENNIFER TOWNESan Diego, USA
Dr. Towne completed her doctoral degree in the Department of Molecular Genetics, Biochemistry, and Microbiology at the University of Cincinnati School of Medicine where she studied the role of aquaporins in pulmonary inflammation and edema. She subsequently joined Immunex as a post-doctoral fellow investigating the role of novel IL-1 family members in physiology and pathophysiology. Dr. Towne was hired at Immunex as a full time scientist and worked at Immunex/Amgen for 13 years focusing first on the biology of IL-1 family members, primarily IL-36, IL-17 family members, and IL-23 in the skin, lung and gut. She led or was a key contributor to multiple large and small molecule project teams currently in clinical development for psoriasis and inflammatory bowel disease (IBD). For the last several years she was responsible for developing the strategy and leading the IBD discovery team at Amgen. Dr. Towne started at Janssen in November 2014 as Scientific Director, Immunology Discovery, where she was responsible for the IBD discovery efforts on the West coast. Dr. Towne is currently the discovery lead for the IBD disease area stronghold across Janssen where she is responsible for discovery efforts to develop innovative therapeutics for the treatment, prevention and cure of IBD. Dr. Towne is a longstanding member of the International Cytokine and Interferon Society (ICIS) and has served as the co-chair of the awards committee and of the publication committee.
ABSTRACT
IL-36α, IL-36β and IL-36γ are members of the IL-1 family of cytokines that signal through a common receptor composed of IL-36R and IL-1RAcP to activate NFκB and mitogen activated protein kinases such as p38 and JNK and promote inflammatory responses. IL-36Ra is a natural antagonist of the three IL-36 agonists that binds to IL-36R, inhibits binding of the agonistic ligands, does not recruit the co-receptor IL-1RAcP and does not stimulate any intracellular responses. These cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells and fibroblasts. Processing of the N-terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response and is implicated strongly through both functional and genetic evidence in the pathology of psoriatic disorders. Emerging data also suggests a role for this cytokine family in pulmonary and intestinal physiology and pathology. Although much has been learned about the biochemistry of IL-36 and its role in various tissues, it is clear that we are at an early stage in our understanding of the full biology of these cytokines.
SPEAKER BIOGRAPHIES
NOTES
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ABBVIE SPONSORED LECTURE
THE EVOLUTION OF T CELL TARGETED THERAPY IN PSORIASIS
PROFESSOR JONATHAN BARKERLondon, UK
Jonathan Barker is Professor of Medical Dermatology and Head of St John’s Institute of Dermatology, King’s College London and honorary consultant dermatologist at Guy’s and St. Thomas’s Hospitals. He specialises in complex hospital based medical dermatology. He is co-director of the severe psoriasis service and Skin Therapy Research Unit. His research extends from genetic discovery through to clinical outcome measurement. It has been funded from multiple sources including European Union, Medical Research Council (MRC UK), National Institute for Health Research, medical charities and industry. He is a key investigator in national and international consortia aiming to identify genetic susceptibility to important chronic skin diseases such as psoriasis, acne and eczema and in biomarker discovery of outcomes to interventions.
Professor Barker is course director of the Institute’s MSc Clinical Dermatology for overseas graduates. This internationally renowned course has existed for more than 40 years and has helped train many dermatologists around the globe extending from the Caribbean through Africa to the Middle and Far East.
Professor Barker has published over 250 peer-reviewed papers, authored and edited several books including the new edition of the ‘Rook Book’- the most comprehensive textbook in the English language. Highly cited publications include those in the Lancet, Nature Genetics and New England Journal of Medicine. He sits on the editorial boards of several dermatology journals. He has delivered plenary keynote lectures at many meetings internationally including Dohi Memorial Lecture at Japanese Dermatology Association in 2016 and Eugene M Farber Oration at Society for Investigative Dermatology, USA in 2017. He is a past President of the European Dermatology Forum and the European Society for Dermatological Research. He is currently President-elect of the International Psoriasis Council. He is an honorary overseas member of the several national dermatological associations including Denmark, Germany, Japan and the USA.
ABSTRACT
Over the last thirty years, in-depth research has revolutionised our understanding of the immunopathogenesis of psoriasis, leading to the discovery of new therapeutic targets and evolving the way we manage our patients. Moving target identification from serendipity to science-driven mechanistic rationale, the development of T cell-targeted therapies has brought new innovations to the management of psoriasis. These innovations have resulted in dramatic clinical advances and have equally created new questions that demand further research. In this lecture, Professor Jonathan Barker will take the audience through a review of the past, present and future of T cell-targeted therapies for psoriasis.
SPEAKER BIOGRAPHIES
As our perception of psoriasis shifted from a skin disease to a systemic, T cell-driven condition involving multiple cytokines, research shone new light onto the recurrent nature of lesions and the psoriasis pathogenesis model. The union of immunology and genetics, enabled the introduction of more specific targeted therapeutic agents, able to alter the T-cell-driven inflammatory cascade associated with T cell activation.As we advance our understanding of psoriasis, we continue to identify even more specific targeted T cell therapies. The potential of IL-23 p19 inhibition underpins one of the latest innovations in psoriasis and may change the way psoriasis is currently managed.
The clinical landscape of psoriasis is changing rapidly, with the introduction of biosimilars alongside the development of new agents with new modes of action, with results that may not be fully explained by our current understanding of the disease.
NOTES
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UCB PHARMA SPONSORED LECTURE
RE-EVALUATING THE ROLE OF IL-17F IN IMMUNE-MEDIATED CHRONIC INFLAMMATION: DUAL NEUTRALISATION OF BOTH IL-17A AND IL-17F AS A NOVEL TARGETING APPROACH IN PSORIATIC DISEASES
DR STEVAN SHAWSlough, UK
Stevan Shaw joined Celltech in 1993 as a research graduate in the immunology therapeutic area. Whilst an employee, he completed his immunology PhD training at Imperial College London focusing on lymphocyte biology; specifically, in vivo functions of Th1 and Th2 cells. Post-PhD training Stevan completed a sabbatical in the USA working in the immunology target discovery department where he designed, developed and implemented in vivo immunology screens for target identification and validation for autoimmune diseases. Post acquisition of Celltech by UCB, Stevan has gained a thorough understanding of antibody-based therapeutics leading projects within the UCB preclinical immunology portfolio and in his functional role as Head of Preclinical Pharmacology. In 2012, Stevan took on the role of leading the UCB4940 clinical programme through to Phase 2b and is now responsible for scientific research to further the understanding of how targeting IL-17A and IL-17F biology may translate into patient value.
ABSTRACT
Identification of immunological pathways pivotal in the pathogenesis of immune-mediated chronic inflammation has led to the development of treatments targeted against key pro-inflammatory cytokines (e.g., TNF, IL-17A and IL-23).1,2 While the benefit of current therapies is evident, achieving and maintaining complete skin clearance remains a challenge; therefore, treatments targeting other mediators of inflammation could provide additional patient value.
Historically, the most extensive research into the IL-17 family of cytokines (IL-17A, IL-17B, IL-17C, IL-17D, IL-17E [also known as IL-25] and IL-17F) has been focused on strategies for the inhibition of IL-17A. However, the role of IL-17F, which shares approximately 50% structural homology and overlapping biological function with IL-17A, has been re-evaluated based on recent insights from murine and human data that suggest it may also play an important role in psoriatic diseases. In this talk, we will discuss the contribution of IL-17F to immune-mediate chronic inflammation and describe the preclinical and early clinical data supporting dual neutralisation of IL-17A and IL-17F as a novel targeting approach in psoriatic diseases.
SPEAKER BIOGRAPHIES
In lesional skin tissue and inflamed synovium from patients with psoriatic arthritis (PsA), similar patterns of expression and upregulation have been demonstrated for IL-17A and IL17F. Moreover, in preclinical models, both IL-17A and IL-17F co-operate with other pro-inflammatory cytokines, such as TNF, amplifying inflammatory responses in a qualitatively similar manner. Dual neutralisation of IL-17A and IL 17F in disease-relevant human cellular systems resulted in reduced expression of inflammation-linked genes and pro-inflammatory cytokines and greater suppression of immune cell migration when compared with IL-17A blockade alone. These data suggest that IL-17F plays an important role in chronic inflammation, beyond that of IL-17A.
IL-25, another member of the IL-17 family of cytokines which is implicated in Th2 responses, which shares a receptor subunit with IL-17A and IL-17F, has been found to indirectly modulate pro-inflammatory cytokine production. Targeted dual neutralisation of IL-17A and IL-17F, without interfering with the function of IL-25, may therefore produce optimal inhibition of IL-17-mediated inflammatory signalling responses in psoriatic diseases.
Given the evidence to support a role for both IL-17A and IL-17F in driving immune-mediated inflammatory diseases, rational design was utilised to generate UCB4940, a humanised immunoglobulin G1 monoclonal antibody that has strong affinity for both cytokines.
The therapeutic potential of UCB4940 has been evaluated in a first-in-human study in patients with mild psoriasis and a proof-of-concept study in patients with moderate-to-severe PsA. In these studies, UCB4940 was associated with a rapid onset of clinically meaningful efficacy and sustained reductions in disease activity measures, with no unexpected safety signals. These preliminary findings suggest that dual neutralisation of IL-17A and IL-17F with UCB4940 may offer a further approach in the treatment of psoriatic diseases.
1. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361:496–509.2. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007;445:866–73.
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NOVARTIS SPONSORED LECTURE
DISEASE MODIFICATION, FROM BEDSIDE TO BENCH
PROFESSOR LARS IVERSENAarhus, Denmark Lars Iversen is the Head of the Psoriasis Clinic at the Department of Dermatology, Aarhus University Hospital and Professor of Dermatology at Aarhus University, Denmark, where he received his medical degree in 1991. In addition to his teaching duties at Aarhus University, Professor Iversen serves as a reviewer of PhD dissertation and doctoral theses at several European institutes.
Professor Iversen has authored more than 160 publications in peer-reviewed journals and is a reviewer for several medical journals including the Nature Immunology, Proceedings of the National Academy of Sciences, the EMBO Journal and Blood. Professor Iversen has received several prizes including the Nordic Prize of Dermatology and Venereology in 2001 and Advances in Psoriasis in 2008. His research interests include all aspects of psoriasis ranging from molecular biology and epidemiological studies, to clinical research. In addition, he is currently conducting research in cutaneous T-cell lymphomas.
ASSOCIATE PROFESSOR LIV EIDSMOStockholm, Sweden
Group leader at Department of Medicine, Karolinska Institutet and practicing dermatologist at Karolinska University Hospital in Sweden. Liv Eidsmo received her MD 1999 and a PhD in Immunobiology in 2006, both from Karolinska Institutet. Following a postdoc in Frank Carbone’s laboratory at Melbourne University, Liv Eidsmo established her own research group in 2010 in Mona Ståhle’s laboratory at Karolinska Institutet and became a board-certified dermatologist in 2017. Dr Eidsmo is a Wallenberg Clinical Fellow, a Ragnar Söderberg Fellow of Medicine and was recently awarded the Ellis and Ivar Janzen prize from the Swedish Society of Medicine.
Dr Eidsmo’s research focus on resident immune cells in human skin. The group recently defined functionally distinct subsets of tissue resident memory T (TRM) cells based on the expression of the integrin CD49a and have characterized pathogenic TRM cells in vitiligo and psoriasis.
SPEAKER BIOGRAPHIES
ABSTRACT
Could early intervention in psoriasis result in and disease modification?Professor Lars IversenAarhus, Denmark
Most published guidelines for the treatment of psoriasis recommend the conventional step-up treatment approach starting with topical treatment and followed by narrow band UVB and/or systemic treatment if the disease is not well controlled. Thus, in recent years there has been an evolving hypothesis in some immune mediated inflammatory diseases like rheumatoid arthritis and Crohn’s disease suggesting that early intensive treatment with biologic drugs can dampen the immune mechanisms that lead to a chronic inflammation. This early and more aggressive treatment approach has been shown to significantly improve long-term outcomes in disease activity in these diseases. 1,2
In this symposium, we will discuss the scientific rational behind the hypothesis that early and more intensive intervention in subjects with new-onset moderate to severe plaque psoriasis may lead to superior outcomes and lasting benefits compared to the traditional step-up treatment approach.
Involvement of skin-resident T cells in relapsing psoriasis.Associate Professor Liv EidsmoStockholm, Sweden
Tissue resident immune cells are crucial components barrier immunity and the human skin harbours a heterogeneous pool of resident memory T (Trm) cells. We recently reported that CD49a marks CD8+ T cells poised to cytotoxicity and IFN-gamma production, while IL-17 producing T cells lacks CD49a-expression in healthy skin. The balance of functionally distinct subsets of resident memory T (Trm) cells is altered in human inflammatory skin diseases. In psoriasis, Trm cells poised to IL-17 are enriched and these cells persist in clinically resolved lesions. Following ex vivo activation, Trm cells from active and resolved psoriasis lesions induce pathogenic tissue responses capable of steering focal pathology 3. Furthermore, pathogenic Trm cell responses are associated with short time in remission following UVB treatment. An ongoing study may offer a possibility to test if the composition and functionality of Trm cells steer recurrent psoriasis in a clinically relevant setting 4.
In this symposium, the pathogenic properties of Trm cells in psoriasis and how early intervention may prevent disbalances in the set-up of Trm cells afflicted skin will be discussed.
References:
1 Smolen et al. Ann. Rheum. Dis. 76; 960–9772 Danese et al. Gut 2017; 0, 1-93 Cheuk et al J Immunology 2014 and Cheuk et a Immunity 2017.4 https://clinicaltrials.gov/ct2/show/NCT03020199?cond=stepin+study&rank=1
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CELGENE SPONSORED LECTURE
THE COMPLEX MANAGEMENT OF PATIENTS WITH PSORIASIS AND COMORBIDITIES: THE ROLE OF THERAPY CHOICE
PROFESSOR PAOLO GISONDIVerona, Italy Professor Paolo Gisondi began his clinical career at the Catholic University of the Sacred Heart in Rome, Italy, where he graduated in Medicine in 1997 and in Surgery in 1998. Subsequently, he worked as a doctor in Rome at the San Gallicano Dermatological Institute-IRCCS and at the Institute of the Immaculate Dermopatico-IRCCS, taking care of hospitalised patients. He specialised in Dermatology and Venereology in 2002 at the Dermatology Clinic of the University of Parma, Italy.
Professor Gisondi began his scientific work at the Institute of the Immaculate Dermopatico-IRCCS, where he was actively involved in clinical dermatology through planning and participation in epidemiological studies, and studies on quality of life in psoriasis, psoriatic arthritis and atopic dermatitis, collaborating with Professor G. Girolomoni. At the same time, he participated as a sub-investigator in research protocols, mainly on clinical biologics in the treatment of psoriasis, and topical calcineurin inhibitors in atopic dermatitis. Since 2005, he has worked at the Dermatology Clinic of the University of Verona, Italy, where he is involved in the design and implementation of epidemiological studies to assess the association between psoriasis and the metabolic syndrome, and therapeutic impact of psoriasis intervention by correcting the underlying metabolic disorders.
ABSTRACT
The clinical presentation of chronic plaque psoriasis is highly variable among patients because of factors such as the age of onset, the involvement of different areas and the severity of the disease. In addition, approximately 40% of patients develop psoriatic arthritis.1 Other comorbidities are also frequently associated with the disease, including metabolic syndrome, obesity, type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular disease.
It is likely that genetic, metabolic and environmental factors contribute to comorbidities in psoriasis patients.2
In particular, emerging evidence suggests that psoriasis and metabolic syndrome share similar pathogenic pathways.2 In this context, adipose tissue has received special attention because of its role as an active endocrine and paracrine organ involved in lipid and glucose metabolism and in the regulation of inflammation.2
SPEAKER BIOGRAPHIES
Psoriasis is a chronic disease with an unpredictable natural history that requires long-term treatment. The presence of comorbidities in psoriasis patients can bring additional levels of complexity to treatment decisions. The long-term use of treatments for psoriasis should take into account this complex picture, and consequently, treatment approaches should be personalised according to the specific characteristics and needs of the patient.3
These elements should be considered in order to achieve optimal care.2
References
1. Husted JA, et al. Arthritis Care Res (Hoboken) 2011;63:1729–1735.2. Gisondi P, et al. Clinics in Dermatology 2017 [Epub] doi: 10.1016/j.clindermatol.2017.09.005.3. World Health Organization - Global report on psoriasis. Available at: http://apps.who.int/iris/ bitstream/10665/204417/1/9789241565189_eng.pdf (Accessed October 2017)
NOTES
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CHALLENGING CONVENTIONAL CLASSIFICATION DOGMA: TOWARDS A NEW CLINICAL TAXONOMY OF PSORIASIS
PROFESSOR ULRICH MROWIETZKiel, Germany
Professor Ulrich Mrowietz is a Dermatologist and Head of the Psoriasis Center at the University Medical Center Schleswig-Holstein, Campus Kiel.
His main scientific and clinical interests are psoriasis and psoriasis management. His recent research focuses on trigger factors for psoriasis, pustular psoriasis and the mechanisms of action of fumarates. He has worked on establishing management procedures for psoriasis that have been included in the first Global Report on Psoriasis by the WHO.
Professor Mrowietz serves as the Editor-in-Chief of the Archives of Dermatological Research. He is an active member of the cluster of excellence “Inflammation at Interfaces” at the University of Kiel, a former member of the Executive Board of the German Dermatological Association (2007-2015), as well as a member of the Scientific Advisory Board of the German Psoriasis Association. He is also a member of numerous national and international Dermatological Societies and a co-author of the German and European Guidelines for the treatment of psoriasis and lead the European Consensus Programme on Treatment Goals in psoriasis. Professor Mrowietz has published more than 270 articles referenced in the Medline data base, and has written numerous chapters in textbooks including “Fitzpatrick’s Dermatology in General Medicine” and Braun-Falco’s “Dermatologie und Venerologie”.
ABSTRACT
Although psoriasis as a disease entity is known since more than hundred years the understanding of its pathogenesis and genetic background is still insufficient as well as their value to the predict the clinical course of disease and response to treatment.
It is of note that the clinical appearance of psoriasis is heterogeneous and in the past a large number of clinical subtypes have been described. Until today there is no international consensus regarding the nomenclature of a clinical classification of psoriasis. Generation of a consensus is hampered by a varying phenotype in different ethnic groups, diverse textbook descriptions and country-specific peculiarities. Phenotypic variability of psoriasis lesions exists not only among different individuals but also within the same patient during the disease course and after trigger factor-induced exacerbations.
SPEAKER BIOGRAPHIES
It is accepted in the dermatological community to separate pustular from non-pustular psoriasis, and early-onset from late-onset disease. However, plaque psoriasis, the prototype of non-pustular psoriasis, may show pustular eruptions during flares. Genetic studies have shown that HLA-C*0602 shows strongest association to plaque psoriasis and may explain at least in part an autoimmunological background of the disease. However, many patients with severe psoriasis lack this genetic marker.
It has been conclusively demonstrated that a number of conditions are associated with psoriasis including psoriatic arthritis, diabetes mellitus, hypertension, dyslipidemia and obesity. The latter represents an independent risk factor for psoriasis and the influence of obesity on the course of disease may be more important as compared to genetic markers.
A consensus definition of the different psoriasis phenotypes and their relation to genetic markers as well as to comorbidity is a major challenge. One initiative, the global psoriasis atlas, may be helpful to generate an inventory of psoriasis phenotypes across different ethnic groups and countries. Together with information about genotype and comorbidity this may help to generate a first unifying clinical taxonomy of psoriasis. As genetic markers and other measures to predict treatment outcomes particularly using targeted therapies have failed so far a more sophisticated clinical definition of psoriasis may fill this gap.
NOTES
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THE PRICE AND VALUE OF BIOLOGIC DRUGS
DR JACK SCANNELLEdinburgh, UK Jack Scannell is co-head European Pharmaceuticals, Investment Research, at UBS Investment Bank. Prior to joining UBS in 2016, Jack consulted to the drug and biotech industry, and to public sector bodies, on R&D productivity and drug pricing. He also conducted academic research on R&D productivity and remains an Honorary Fellow at the University of Edinburgh, and an Associate of CASMI at Oxford University. From 2012 to 2014, Jack was Head of drug discovery at a e-Therapeutics PLC, a bio-informatics based biotechnology firm, that sought to exploit analytic methods he had worked on as an academic, in the late 1990s. From 2005 to 2012, Jack was an investment analyst. He led the European Healthcare team at Sanford Bernstein in London. He has a degree in Medical Sciences from Cambridge University and a PhD in Physiology (Computational Neuroscience) from Oxford University.
ABSTRACT
If I offered to buy your shoes you would think I was strange, but we could probably haggle a price. If I offered to buy your children, we would not get to the haggling stage. The difference between trading shoes and children is not merely legal. It is also moral. People find it unpalatable, even taboo, to put prices on things that we treat as absolutes; life, liberty, or health. People have moral qualms about the cost of medicines for the genuinely sick, but not about the cost of Botox or liposuction. Yet medicines do not exist in a parallel universe, free from economics. Taxes are paid, as are health insurance premiums; healthcare budgets are set; doctors earn money; professors seek riches as biotech entrepreneurs; venture capitalists gamble other people’s money on the professors’ ideas; drug companies pay wages to employees and dividends to shareholders. Moral queasiness tends to reduce the quality of, and polarize, public debate on drug pricing. “Cost”, “value”, “power” and “prizes” are four ways that people think, talk or write about the mechanism by which drugs are priced. “Cost” refers to cost-based pricing; the idea that the price of goods is based on how much it costs to produce them. “Value” refers to value-based pricing; the idea that the price of goods reflects their value to the buyer. “Power” is the exercise of intellectual property rights, to create scarcity and to find the maximum price that the market will bear. “Prizes” are the incentives provided by profit tomorrow, made credible by profit today, for investors gambling on the R&D that might create tomorrow’s drugs. At present, “Value” seems the intellectually fashionable approach. In the talk, I will argue that value-based pricing appeals to the drug industry and some health economists, but that it can be bad public policy.
SPEAKER BIOGRAPHIES
NOTES
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SYSTEMS MEDICINE, BIG DATA AND SCIENTIFIC WELLNESS ARE TRANSFORMING HEALTHCARE
DR LEROY HOODSeattle, USA
Dr. Leroy E. Hood graduated from the Johns Hopkins University School of Medicine in 1964 with an MD and from Caltech with a PhD in biochemistry in 1968. After three years as a Senior Investigator at NIH, his academic career began at Caltech, where he and his colleagues developed the DNA gene sequencer and synthesizer, and the protein synthesizer and sequencer–four instruments that paved the way for the successful mapping and understanding of the human genome. A pillar in the biotechnology field, Dr. Hood has played a role in founding fifteen biotechnology companies including Amgen, Applied Biosystems, Integrated Diagnostics and Arivale. He is a member of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. Of the more than 6,000 scientists world-wide who belong to one or more of these academies, Dr. Hood is one of only fifteen people nominated to all three. Dr. Hood has co-authored numerous textbooks in biochemistry, immunology, molecular biology and genetics, as well as a popular book on the human genome project, The Code of Codes and he is just finishing up a text on systems biology. He is the recipient of numerous national and international awards, including the Lasker Award for Studies of Immune Diversity (1987), the Kyoto Prize in advanced technology (2002), the Heinz Award for pioneering work in Systems Biology (2006), and the coveted NAE 2011 Fritz J. and Delores H. Russ Prize for developing automated DNA sequencing. In addition to having received 17 honorary degrees from prestigious universities in the U.S. and abroad, Dr. Hood has published over 750 peer-reviewed articles and currently holds 36 patents. In 2013, he received the National Medal of Science from President Obama. Hood has been named by The Best Schools as one of the 50 Most Influential Scientists in the World Today (2014) http://isb.io/top50. Scientific American has named Hood as one of the top 6 in their selection of 100 biotech visionaries world-wide (2015) http://isb.io/visionary.
ABSTRACT
Systems medicine, the application of systems approaches to disease, places medicine at a fascinating tipping point—promising a revolution in the practice of healthcare. I will discuss how systems biology approaches have framed systems medicine and I will discuss some of the new systems-driven technologies and strategies that have catalyzed this tipping point. Moreover, four converging thrusts—systems medicine, big data (and its analytics), the digitalization of personal measurements and patient-activated social networks—are leading to a proactive healthcare that is predictive, personalized, preventive and participatory (P4). I will contrast P4 healthcare with contemporary medicine and discuss its societal implications for healthcare. P4 healthcare has two central thrusts—wellness and disease.
SPEAKER BIOGRAPHIES
I will discuss our successful effort to introduce P4 healthcare into the current healthcare system with a P4 pilot program on scientific wellness—a longitudinal, high-dimensional data cloud study on each of 108 well patients over 2014. The preliminary results both with regard to data analyses and patient responses from these studies are striking. They point to the emerging discipline of scientific wellness—and the fact that it will catalyze several new thrusts in healthcare: 1) optimizing wellness, 2) identifying the earliest disease transitions for all common diseases and learning how to reverse them and 3) employing the dense, dynamic, personal data cloud approach to study diseases (e.g. cancer, Alzheimer’s, diabetes) and their responses to therapy. Scientific wellness will also pioneer N=1 experiments to deconvolute the staggering complexity of human biology and disease. We started Arivale, a company focused on scientific wellness for the consumer, in 2015 and already have about 4000 individuals enrolled. I will also discuss some preliminary results from the Arivale studies.
My institute, the Institute for Systems Biology (ISB), in 2016 affiliated with Providence St. Joseph Health to become its research arm and I became its Chief Science Officer. Providence is one of the largest non-profit healthcare systems in the US—and ISB/Providence will be initiating a series of “translational pillars” moving applications of systems (P4) medicine from the bench to the bedside. These pillars include scientific wellness, bringing scientific wellness to cancer survivors, making Alzheimer’s a reversible and preventive disease, rather than a relentlessly progressive disease, taking a systems approach to type 2 diabetes and exploring how the deep, dynamic, personal data clouds can be used to gain a deep understanding of glioblastoma and provide new diagnostic and therapeutic approaches to this inevitably fatal tumor. It is fair to say that dense, dynamic, personal data clouds followed longitudinally on hundreds of thousands of patients/consumers will allow us to see the earliest wellness to disease transitions for all of the common cancers—and generate biomarkers for early detection and identify the drug targets or strategies (e.g., immunotherapy) that will allow us to reverse the disease before it ever manifests itself as a disease phenotype. Systems medicine, P4 healthcare and scientific wellness will open up powerful new approaches to dealing with diseases of the skin—including psoriasis.
Thus scientific wellness will catalyze a transformation in contemporary healthcare and it will provide eventually millions of dense, dynamic, personal data clouds that will present striking new opportunities for pharma, biotech, nutrition and diagnostic companies to identify biomarkers and drug target candidates. As the cost of the assays for the dense, dynamic, personal data clouds decline dramatically; scientific wellness can be brought to the developing world leading to a democratization of healthcare unimaginable even a few years ago.
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ABSTRACTSBJD
British Journal of Dermatology
Psoriasis Gene to Clinic, 8th International Congress. TheQueen Elizabeth II Conference Centre, London, U.K.,30th November – 2nd December 2017
Free communicationsFC01Psoriasis and risk of malignant lymphoma:a population-based cohort studyM. Kamstrup, L. Skov, C. Zachariae, J. Thyssen andA. EgebergDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital,
Hellerup, DenmarkPsoriasis is a chronic proliferative inflammatory skin disease.
Epidemiological studies have suggested an association between
psoriasis and lymphoma, but data are limited. The aim of the
study was to quantify the 5-year risks of new-onset Hodgkin
lymphoma (HL), non-Hodgkin lymphoma (NHL) [excluding
cutaneous T-cell lymphoma (CTCL)] and CTCL in patients with
psoriasis. We performed a Danish nationwide cohort study
including data on all individuals aged ≥ 18 years between 1 Jan-
uary 2008 and 31 December 2012. Incidence rates (IRs) per
10 000 person-years for HL, NHL and CTCL were calculated,
and hazard ratios (HRs) with 95% confidence intervals (CIs)
were obtained using Cox regression analysis and adjusted for
age, sex, socioeconomic status and systemic treatment. The pso-
riasis cohort was stratified according to severity by systemic
antipsoriatic therapy. In total 58 138 patients with psoriasis and
4 303 731 general population controls were identified. The IRs
in patient with psoriasis for HL (IR 1.02, 95% CI 0.70–1.47),NHL (IR 4.04, 95% CI 3.36–4.87) and CTCL (IR 0.44, 95% CI
0.25–0.77) were higher among patients with psoriasis than in
the general population. Adjusted HRs revealed significant associ-
ations between psoriasis and HL (HR 1.50, 95% CI 1.01–2.23)but not NHL (HR 1.02, 95% CI 0.84–1.24) or CTCL (HR 1.66,
95% CI 0.88–3.13). When stratified by disease severity, adjusted
HRs were significant for mild psoriasis and HL (HR 2.08, 95%
CI 1.38–3.15) and for severe psoriasis and NHL (HR 1.64, 95%
CI 1.12–2.40) and CTCL (HR 13.63, 95% CI 6.72–27.64). Inconclusion, patients with severe psoriasis have a higher co-
occurrence of NHL and especially CTCL than the general popula-
tion. Patients with mild psoriasis have a slightly increased risk of
HL. The relative contributions of an initial incorrect diagnosis,
possible overlap in disease pathogenesis, and complications of
systemic medication need further investigation.
FC02Developing a therapeutic range and predictingresponse to biologics in patients with psoriasis: amulticentre prospective observational cohort studyT. Tsakok and the PSORT ConsortiumKing’s College London and St John’s Institute of Dermatology, London, U.K.
Biological therapies have transformed treatment in immune-
mediated inflammatory diseases, yet significant numbers of
patients experience treatment failure. Variability in drug levels
correlates with outcomes across multiple inflammatory dis-
eases, but with limited data in psoriasis. In this prospective
observational cohort study (60 dermatology specialist centres)
we determine the clinical utility of therapeutic drug monitor-
ing using the exemplar tumour necrosis factor antagonist
adalimumab. Adults (n = 515) recruited to Biomarkers of Sys-
temic Treatment Outcomes in Psoriasis (BSTOP) within the
biologics pharmacovigilance British Association of Dermatolo-
gists Biologic Interventions Registry (BADBIR) with serial
adalimumab level measurements up to 1 year were included
(888 samples; 63% male; mean age 44 � 12 years).
Response to treatment at 6 months was defined as ≥ 75%
improvement in Psoriasis Area and Severity Index (PASI 75;
primary outcome). We found that drug level can discriminate
responders from nonresponders with a minimally effective
adalimumab level identified as 3.3 lg mL�1 [sensitivity 80%;
specificity 57%; area under the curve 0.73, 95% confidence
interval (CI) 0.67–0.79]. Multilevel mixed-effect logistic
regression modelling to account for clustering of samples
within patients, and to adjust for covariates, indicates that a
target drug level of 7 lg mL�1 will achieve a minimum 80%
probability of response (81%, 95% CI 76–86). Early serum
drug level was confirmed as an additional independent indica-
tor of 6-month PASI 75 response [OR(√drug level) 1.95, 95%
CI 1.06–3.57, P = 0.031] and PASI 90 response [OR(√drug
level) 2.38, 95% CI 1.26–4.50, P = 0.008], substantially
improving the model’s goodness of fit. Smoking and disease
duration were also key baseline predictors influencing
interindividual variation. This real-world study with pragmatic
drug level sampling provides strong evidence to support
proactive measurement of drug levels in the management of
psoriasis, and highlights the importance of taking drug levels
into account when searching for biomarkers of treatment
response.
FC03The differential production of interleukin (IL)-26 vs.IL-17 by T helper 17 cells contributes to thedevelopment of different forms of psoriasisA. Fries, J. Di Domizio, O. Demaria and M. GillietUniversity Hospital Lausanne, Lausanne, SwitzerlandInterleukin (IL) 17-producing helper T cells (Th17 cells) play
a role in protection against infections and have also been
linked to autoimmune diseases like psoriasis. Th17 cells pro-
duce IL-17A/F, IL-22 and IL-26. Whereas the induction of
© 2017 British Association of Dermatologists British Journal of Dermatology (2017) 1
IL-17 and IL-22 expression during Th17 differentiation has
been well described, the mechanism regulating the production
of IL-26 remains ill defined. Here, we found that IL-6 alone is
required to generate IL-26-producing T cells from naive T
cells, but it is not sufficient to induce IL-17-producing T cells.
By contrast, the generation of IL-17-producing T cells required
the presence of IL-1 and IL-23, which are unable to induce
IL-26, suggesting that Th17 cells comprise two distinct sub-
sets, namely IL-26-producing T cells and IL-17-producing T
cells. Although all Th17 cytokines are elevated in psoriasis, we
also found a dichotomy between IL-17 and IL-26 expression
in the skin of different forms of the disease. Whereas IL-17
was mainly associated with chronic plaque psoriasis, IL-26
appeared to be strongly expressed in more acute lesions (ery-
throdermic psoriasis, guttate psoriasis, paradoxical psoriasis).
Importantly, the expression of IL-26 in psoriasis correlated
with the expression of IL-6 but not IL-1 nor IL-23, indicating
that the presence of IL-26-producing T cells may drive the
development of acute skin inflammation. These findings there-
fore identify IL-26 as a novel therapeutic target for the treat-
ment of acute forms of psoriasis.
FC04Psoriasis-associated late cornified envelope)proteins have antibacterial activityH. Niehues,1 L. Tsoi,2,3,4 D. van der Krieken,1
P. Jansen,1 M. Oortveld,1 D. Rodijk-Olthuis,1 I. vanVlijmen-Willems,1 W. Hendriks,5 R. Helder,6
J. Bouwstra,6 R. Mesman,7 L. van Niftrik,7 E. van denBogaard,1 P. Stuart,2 R. Nair,2 J. Elder,2,8
P. Zeeuwen1 and J. Schalkwijk11Department of Dermatology and 5Department of Cell Biology, Radboud
University Medical Centre, Radboud Institute for Molecular Life Sciences,
Nijmegen, the Netherlands; 2Department of Dermatology, 3Department of
Computational Medicine and Bioinformatics and 4Department of Biostatistics,
University of Michigan, MI, U.S.A.; 6Leiden Academic Center for Drug
Research, Department of Drug Delivery Technology, Gorlaeus Laboratories,
Leiden University, Leiden, the Netherlands; 7Department of Microbiology,
Institute for Water and Wetland Research, Faculty of Science, Radboud
University, Nijmegen, the Netherlands and 8Ann Arbor Veterans Affairs
Hospital, Michigan, MI, U.S.A.Late cornified envelope (LCE) genes, located in the epidermal
differentiation complex on chromosome 1, encode a family of
18 proteins of unknown function, whose expression is largely
restricted to the epidermis. Deletion of two members, LCE3B
and LCE3C (LCE3B/C-del), is a widely replicated psoriasis risk
factor that interacts with the major psoriasis-risk gene HLA-
C*06:02. Disease-associated genetic risk factors often involve
noncoding variants, which has precluded understanding of
their functional consequences in complex diseases. We aimed
to investigate the expression and function of the LCE proteins
to explain the biology that underlies the association between
LCE3B/C-del and psoriasis. We used cis-expression quantitative
trait locus analysis and functional assays of LCE proteins in
in vivo skin and three-dimensional epidermal models. RNA-seq
data from normal and psoriatic human skin revealed that
LCE3B/C-del was associated with a significant induction of
LCE3A, directly adjacent to LCE3B/C-del. This phenomenon was
most strongly present in normal skin, where the LCE3A gene
is silent when LCE3B and LCE3C are present. We confirmed
these findings in a three-dimensional epidermal equivalent
model using primary keratinocytes from LCE3B/C-del geno-
typed donors. Functional analysis did not support a role for
LCE proteins in epidermal barrier function, but revealed that
psoriasis-associated LCE3 proteins, and LCE3A in particular,
have defensin-like antimicrobial activity against a broad variety
of bacterial taxa at low micromolar concentrations. Our find-
ings identify a hitherto unknown biological function for LCE3
proteins and suggest a central role for LCE3A in epidermal
host defence and LCE3B/C-del-mediated psoriasis risk.
FC05Environmental antigens may trigger HLA-C*06:02-mediated autoimmunity in psoriasisY. Arakawa, A. Arakawa, S. Vural, A. Galinski,S. Vollmer and J. PrinzDepartment of Dermatology, Ludwig-Maximilian-University of Munich,
Munich, GermanyPsoriasis vulgaris is a human leucocyte antigen (HLA)-
C*06:02-associated T-cell-mediated autoimmune skin disease
that develops upon epidermal infiltration and activation of
CD8+ T cells. Environmental and lifestyle factors may trigger
disease onset, and account for approximately 30% of disease
risk. Using a Va3S1/Vb13S1 T cell receptor (TCR) from a
pathogenic epidermal psoriatic CD8+ T-cell clone we have
recently shown that in psoriasis HLA-C*06:02 mediates an
autoimmune response against melanocytes, and we had identi-
fied a peptide from ADAMTS-like protein 5 as a melanocytic
antigen. In this study, we aim to identify environmental fac-
tors at the molecular level that translate the genetic predisposi-
tion into disease manifestation. TCRs are polyspecific. They do
not recognize specific antigens but react against HLA-presented
peptides sharing a particular amino acid pattern specific to this
TCR. After defining the amino acid pattern recognized by the
Va3S1/Vb13S1 TCR in the context of HLA-C*06:02 by pep-
tide library screening we searched environmental proteomes
for peptides sharing this particular pattern. Environmental can-
didate epitopes were tested for their ability to ligate the
ADAMTSL5-reactive Va3S1/Vb13S1 TCR when presented by
HLA-C*06:02. This way we identified a variety of peptides
contained in proteins from human skin and gut microbiomes,
from infectious pathogens including Chlamydia trachomatis, and
from foods (wheat, coffee, apple and spinach) that ligated the
Va3S1/Vb13S1 TCR. These results provide the first evidence
of environmental antigens that may serve as potential triggers
of the melanocyte-specific autoimmune response in psoriasis.
They suggest that exposure to environmental antigens may
drive priming and expansion of potentially self-reactive T cells
and thus initiate autoimmune disease responses. Through the
unbiased analysis of a pathogenic psoriatic TCR our data fur-
thermore may have important implications in understanding
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
2 Psoriasis Gene to Clinic
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from gene to clinic
61ABSTRACTS
how environmental factors affect the risk for autoimmune dis-
eases in general.
FC06Analysis of psoriasis host-microbiome interactionsusing a universal transcriptomic approachT. Furnholm, M. Foo, J. Henderson, K. Shedden andA. JohnstonUniversity of Michigan, Ann Arbor, MI, U.S.A.Perturbations in host–microbe interactions may underlie the
triggering and worsening of psoriasis. 16S DNA sequencing
has indicated that psoriatic skin and tonsils have markedly
altered microbiomes; however, this method identifies bacteria
poorly and does not inform about altered microbial function.
The use of next-generation RNA sequencing (RNA-seq) to
study the actively transcribed genes from a microbial commu-
nity is currently hindered because existing alignment software
was designed for single-organism analysis. Thus, we devel-
oped new RNA-seq alignment software, Muscato, specifically
designed to carry out multigenome sequence alignment. Mus-
cato aligns hundreds of millions of RNA-seq reads to hundreds
of millions of genes in reasonable time frames and needs only
modest computational resources. When coupled to a func-
tional and taxonomic annotated gene database it allows simul-
taneous analysis of host and microbe gene expression. To
identify host–microbe interactions that may drive psoriasis,
we performed RNA-seq analysis on lesional skin (LS, n = 11),
nonlesional skin (NLS, n = 10) and tonsils (PT, n = 11) of
patients with psoriasis and normal controls (NS, NT n = 7). In
LS, 799 differentially expressed (more than twofold) human
genes mapped to KEGG functions including inflammation
(IL1B, IL8, NFKB1, TLR4), keratinocyte proliferation (EGF,
STAT3, CCND1, MYC), vascularization (VEGF, TEK, ANGPT1),
and T-cell responses (TGFB1, ITGB2, ICAM1, SGK1). This was
accompanied by reduced microbial diversity (Shannon Index:
LS 7.2, NLS 8.6, NS 8.3), with decreased Propionibacterium and
more than fourfold increased Streptococcus pyogenes colonization.
Nine of 64 (LS) and 40 of 90 (PT) streptococcal species were
more than twofold more abundant than in controls, with
S. anginosus and S. parasanguinis predominant. Multiple streptococ-
cal species had differentially expressed (more than fivefold)
virulence factors, including sialidase (NEU1, PT) streptolysin O
(Slo, LS), haemolysin (HlyC, PT and LS), exfoliative toxin (EtaA,
PT and LS), antimicrobial peptide resistance (DltA-D, PT and
LS), sec- and Type IV protein secretion systems and secreted
proteases, which may drive T-cell skin homing and activation.
Psoriasis tonsils yielded 333 other differentially abundant
microbial taxa, including Tannerella forsythia, Bulleidia extructa
W1219, Dialister invisus, Gemella sanguinis and Staphylococcus sciuri,
already implicated in inflammatory diseases (arthritis, endo-
carditis, atherosclerosis, periodontitis). Our novel RNA-seq
pipeline revealed enriched streptococcal superantigens in pso-
riatic skin and tonsils, together with species-level identification
of streptococci and other invasive bacteria that could drive
psoriasis and its comorbidities.
FC07Genetic variation contributes to response tobiologics: initial findings of the PsoriasisStratification to Optimise Relevant Therapy(PSORT) consortiumN. Dand on behalf of the PSORT consortiumKing’s College London, London, U.K.Biological therapies, which target specific components of key
proinflammatory immune pathways, can be highly effective in
the treatment of moderate-to-severe psoriasis. However, fail-
ure to respond carries a high cost, both economically and in
terms of patient care. The PSORT consortium therefore aims
to identify predictors of treatment response in psoriasis
patients. To date we have genotyped 3320 patients enrolled in
the British Association of Dermatologists Biologic Interventions
Register (BADBIR) using the Illumina OmniExpressExome
BeadChip. We further imputed human leucocyte antigen
(HLA) status for key alleles, including HLA-C*06:02, using
SNP2HLA software. For all patients the BADBIR register
includes detailed records of treatments, Psoriasis Area and
Severity Index (PASI) disease severity scores, and additional
demographic and clinical measurements. In an initial cohort
of 2467 patients we examined associations with biological
response reported in previous candidate variant studies. These
investigations have focused on genes implicated in psoriasis
susceptibility, biological response in other diseases, or drug
target pathways, but are yet to form a clear picture of how
genetic variants contribute to treatment response. For anti-
tumour necrosis factor (anti-TNF) (adalimumab, etanercept
and infliximab) and anti-interleukin (IL)-12/23 (ustek-
inumab) drugs we tested these variants for association with
response in patients with severe disease (baseline PASI > 10).
Response was defined at 3, 6 and 12 months as a 50%, 75%,
90% or 100% reduction in PASI relative to baseline. We found
modest evidence to support opposing roles for HLA-C*06:02under the two mechanisms of action, with presence of the
allele being positively associated with early response to ustek-
inumab (PASI 75 and 90 at 3 months; P < 0.01) but nega-
tively associated with excellent longer-term response to anti-
TNF agents (PASI 90 and 100 at 12 months, P < 0.01). We
also validate findings that link biological response with estab-
lished psoriasis susceptibility loci, such as TRAF3IP2 in the IL-
17 signalling pathway (adalimumab) and the LCE3B and LCE3C
genes within the epidermal differentiation complex (anti-
TNFs). However, our initial genome-wide results indicate the
presence of previously unreported genetic loci that display
stronger association with biological response. As our unique
datasets continue to accrue we expect our statistical power to
allow identification of novel genetic associations to improve.
We will subsequently examine in detail the interplay between
genetics and patient-specific clinical and demographic factors,
with the aim of predicting response and stratifying patients
according to their most likely effective biologic.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 3
FC08Comparative evaluation of cellular and molecularchanges associated with response to selectiveinterleukin (IL)-23 blockade vs. dual IL-12/23blockade in psoriasis skinK. Li,1 K. Campbell,1 S. Garcet,2 C. Brodmerkel1 andJ. Krueger2
1Janssen Research & Development, LLC, Spring House, PA, U.S.A.,2Laboratory for Investigative Dermatology, The Rockefeller University, New
York, NY, U.S.A.Emerging clinical data indicate that selective blockade of inter-
leukin (IL)-23 can achieve greater efficacy than dual blockade
of IL-12/23 in patients with moderate-to-severe psoriasis.
Ustekinumab targets the p40 subunit common to IL-12 and
IL-23, whereas guselkumab specifically targets the IL-23-speci-
fic p19 subunit. While differences in antibody potency may
explain therapeutic differences between ustekinumab and
guselkumab, we explored cellular and molecular changes in
the skin of patients with psoriasis treated with ustekinumab
or guselkumab to understand the mechanism underlying
selective IL-23 p19 inhibition. Ustekinumab data were derived
from the ACCEPT study (NCT00454584, n = 85), in which
patients with psoriasis received either 45 mg or 90 mg of
ustekinumab at weeks 0 and 4, and guselkumab data were
from the phase I psoriasis study (NCT00925574, n = 24) that
tested single subcutaneous doses of guselkumab. Skin biopsies
were collected at baseline and weeks 1 and 12 post-treatment
from each study to evaluate (i) histological improvement via
epithelial thickness, T cells (CD3) and myeloid dendritic cell
(CD11c) counts and (ii) molecular response to drug via
microarray. Biopsies from healthy volunteers served as con-
trols. The guselkumab 100-mg and 300-mg groups were
combined to increase analytical power. The IC50 of each drug
was evaluated by cell-based bioassays. The two cohorts are
comparable in baseline demographics, disease characteristics,
skin histopathology, psoriasis lesional molecular expression
profiles and significantly enriched canonical pathways. Block-
ade of IL-23 with guselkumab resulted in a significantly
greater reduction in CD3 and CD11c counts in the skin at
week12 relative to baseline when compared with ustekinumab
blockade (> 90% vs. ~70%). In patients who achieved > 50%
improvement in PASI score, guselkumab (n = 9) showed a
larger impact on the psoriasis transcriptomic profile than
ustekinumab 90 mg (n = 12) by week 1 and greater enhance-
ment was achieved by week12. Guselkumab neutralized 74%
of the psoriasis disease profile by> 80%, while ustekinumab
resolved only 21% at week 12. Expression of psoriasis disease
markers such as defensin-beta 4A and lipocalin 2 were fully
resolved by guselkumab beyond the level observed in nonle-
sional skin of patients with psoriasis, while ustekinumab
resolved these markers by only 32% and 63%, respectively. In
vitro, guselkumab showed higher potency (2–14 fold) than
ustekinumab in inhibiting IL-23 activity, which may con-
tribute to stronger neutralization of psoriasis disease markers
by guselkumab. This comparative study demonstrates that
guselkumab inhibits psoriasis-associated pathology and
resolves the skin transcriptomic psoriasis disease profile more
strongly than ustekinumab.
FC09Functional immunophenotyping analysis revealsadalimumab-induced impairment of tumournecrosis factor signalling in lymphoid cells inpsoriasisR.A. EjarqueOn behalf of the PSORT Consortium, London, U.K.Biological treatments have revolutionized the treatment of pso-
riasis. However, up to 30% of patients fail to respond, there-
fore there is a need to identify biomarkers to help direct
personalized treatments. The Psoriasis Stratification to Optimise
Relevant Therapy (PSORT) consortium is aimed at better
understanding the determinants of response to biological ther-
apies and delivering a stratifier algorithm to guide psoriasis
management. In our functional immunophenotyping
approach, we hypothesize that monitoring key transcription
factors downstream of the cytokines being targeted by biologi-
cal treatments provides insights into disease pathogenesis, as
well as biomarkers of disease and response to treatment. Here,
we investigate adalimumab, a tumour necrosis factor (TNF)-
targeting biological agent widely used for the treatment of
psoriasis. We evaluated the nuclear translocation of nuclear
factor (NF)-jB in key immune cell subsets, using imaging
flow cytometry. Fresh blood obtained from patients with pso-
riasis (n = 20) before treatment (baseline) and at weeks 1, 4
and 12 after commencing treatment, was stimulated with
TNF, interleukin (IL)-17, TNF + IL-17 and lipopolysaccharide
(LPS) for 30 min, stained and analysed. NF-jB translocation
was quantified using Fisher’s discriminant ratio (Rd score). At
baseline NF-jB translocation was observed upon TNF stimula-
tion in T cells (Rd 1.21 � 0.10), skin homing CLA+ T cells
(1.12 � 0.08), natural killer (NK) cells (0.85 � 0.15), NKT
cells (1.11 � 0.21), dendritic cells (DCs) (0.80 � 0.08),
monocytes (0.81 � 0.12) and neutrophils (0.49 � 0.10);
and upon LPS stimulation in monocytes (0.98 � 0.17), DCs
(0.42 � 0.07) and neutrophils (0.44 � 0.11). In contrast,
IL-17 stimulation did not induce NF-jB translocation, or aug-
ment the TNF-induced signal in any cell subset. Following
adalimumab, TNF-induced NF-jB translocation was almost
completely inhibited at each time point in T cells, CLA+
T cells, NK cells and NKT cells (92%, 89%, 81% and 84%,
respectively, at week 1, P < 0.01), and to a much lesser extent
in DCs and neutrophils (55% and 29% at week 1, P < 0.05),
while there was no effect in monocytes. In contrast, LPS-
induced NF-jB translocation was not affected by adalimumab
in monocytes, neutrophils and DCs. Interestingly, inhibition
of TNF-induced NF-jB translocation did not correlate with
the midterm response to the treatment, defined as ≥ 75%
improvement in Psoriasis Area and Severity Index (PASI 75)
and relative PASI, at any of the time points tested. Taken
together, these data suggest that the TNF inhibition exerted by
adalimumab in psoriasis mainly affects cells of the lymphoid
lineage, although this mechanism does not seem responsible
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
4 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
63ABSTRACTS
for the clinical response to therapy. Further phenotypic and
functional analysis are ongoing to address the molecular
mechanisms underpinning the clinical response to adalimumab
and to identify biomarkers of response.
FC10The genetic basis for most patients with pustularskin disease remains elusiveU. Huffmeier,1 S. L€ohr,1 P. Schulz,2 A. K€orber,3
J.C. Prinz,4 K. Sch€akel,5 S. Philipp,6 K. Reich,7
H. St€ander,8 A. Jacobi,9 K. Kingo,10 S. Koks,11
S. Gerdes,12 T. Schill,13 K.G. Griewank,3 S. Frey,14
K. Steinz,12 S. Uebe,1 M. Sticherling,15 H. Sticht,16
P. Gkogkolou,17 V. Oji,17 D. Wilsmann-Theis18 andR. M€ossner131Human Genetics, FAU Erlangen-N€urnberg, Erlangen, Germany; 2Fachklinik
Bad Bentheim, Bad Bentheim, Germany; 3Department of Dermatology,
University Hospital, Essen, Germany; 4Department of Dermatology,
University Hospital, Munich, Germany; 5Department of Dermatology,
University Hospital, Heidelberg, Germany; 6Department of Dermatology,
University Hospital, Berlin, Germany; 7Dermatologikum, Hamburg,
Germany; 8Department of Dermatology, Klinikum, Dortmund, Germany;9Institute for Health Services Research in Dermatology and Nursing,
University Medical Center Hamburg-Eppendorf, Hamburg, Germany;10Department of Dermatology and 11Department of Pathophysiology,
University of Tartu, Tartu, Estonia; 12Department of Dermatology,
University Hospital, Kiel, Germany; 13Department of Dermatology, University
Hospital, G€ottingen, Germany; 14Department of Immunology and Medicine
and 15Department of Dermatology, University Hospital, Erlangen, Germany;16Bioinformatics, Department of Biochemistry, FAU Erlangen-N€urnberg,
Erlangen, Germany; 17Department of Dermatology, University Hospital,
M€unster, Germany and 18Department of Dermatology, University Hospital,
Bonn, GermanyRare variants in the genes IL36RN, CARD14 and AP1S3 have
been identified as causing or contributing to pustular skin dis-
eases, primarily generalized pustular psoriasis (GPP). To
understand better the disease relevance of these genes, we
screened our cohorts of patients with pustular skin diseases
[primarily GPP and palmoplantar pustular psoriasis (PPP)] for
coding changes in these three genes. Carriers of single
heterozygous IL36RN mutations were screened for a second
mutation in IL36RN. Coding exons of IL36RN, CARD14 and
AP1S3 were sequenced in 67 patients: 61 with GPP, two with
acute generalized exanthematous pustulosis and four with
acrodermatitis continua suppurativa Hallopeau. We screened
IL36RN and AP1S3 for intragenic copy-number variants, with
258 patients with PPP screened for coding changes in AP1S3.
Eleven heterozygous IL36RN mutations carriers were analysed
for a second noncoding IL36RN mutation. Genotype–pheno-type correlations in carriers and noncarriers of IL36RN muta-
tions were assessed within the GPP cohort. The majority of
patients (GPP, 64%) did not carry rare variants in any of the
three genes. Biallelic and monoallelic IL36RN mutations were
identified in 15 and five patients with GPP, respectively. Non-
coding rare IL36RN variants were not identified in hetero-
zygous carriers. The only significant genotype–phenotype
correlation observed for IL36RN mutation carriers was early
age of disease onset. Additional rare CARD14 or AP1S3 variants
were identified in 15% of IL36RN mutations carriers. The iden-
tification of IL36RN mutation carriers harbouring additional
rare variants in CARD14 or AP1S3 indicates a more complex
mode of inheritance in pustular psoriasis. Our results suggest
additional disease-causing genetic factors in heterozygous
IL36RN mutation carriers outside IL36RN.
FC11ADAM17 and TIMP3 are psoriasis-relevantcheckpoints controlling T helper 17 programmingby inflammatory dermal dendritic cellsA. Kunze,1 A. Rendon,1 S. Oehrl,1 G. Murphy,2
A. Enk1 and K. Schakel1
1Department of Dermatology, Heidelberg, Germany and 2Cancer Research
U.K. Cambridge Institute, Cambridge, U.K.Psoriasis is a chronic inflammatory skin disease in which acti-
vated 6-sulfo-LacNAc-expressing (slan) dendritic cells
(slanDCs) function as inflammatory dermal dendritic cells
(DCs). slanDCs have a high interleukin (IL)-23-, IL-12-, IL-
1b- and tumour necrosis factor-a- producing capacity and
thereby programme T helper (Th)17/Th1-dominated T-cell
responses. Recently, an imbalance of expression of ADAM17
expression and its inhibitor tissue inhibitor of metallopro-
teinases (TIMP)3 was found in the epidermal compartment in
psoriasis, and restoration of TIMP3 levels induced regression
of skin lesions. We here examined the functional relevance of
ADAM17 for inflammatory dermal DCs in psoriasis. We
demonstrate by immunofluorescent staining and polymerase
chain reaction a downregulation of the endogenous ADAM17
inhibitor TIMP3 in both the dermis and the epidermis.
slanDCs but not CD1c+ DCs or CD141+ DCs were found to
express cell-surface ADAM17 as revealed by flow cytometry.
Furthermore, the enzymatic activity of ADAM17 on slanDCs
could be demonstrated by a specific fluorescence peptide
assay. Addition of the endogenous protease inhibitor TIMP3 to
slanDCs inhibited ADAM17 activation, and, most interestingly,
it blocked lipopolysaccharide-induced IL-23 and IL-12 produc-
tion by 60–70%; identical results were obtained with a highly
specific ADAM17-blocking antibody D1A12. To investigate the
biological relevance of these findings in the context of psoria-
sis, we set up cocultures of CD4+ T cells from patients with
psoriasis stimulated with allogeneic slanDCs in the presence of
the specific ADAM17-blocking antibody D1A12. A restimula-
tion of these cultures after 7 days revealed a largely reduced
IL-17 production of T cells, which was identical to the effects
achieved with an IL-12/IL23p40-specific antibody. In conclu-
sion, we identified the protease inhibitor TIMP3 as having
profound ADAM17-dependent immunoregulatory effects at
the level of inflammatory dermal DCs.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 5
FC12Genotype and phenotype analyses revealed novelsusceptibility genes and new clinical classificationfor psoriasisB.-J. Feng,1,2 S. McCarthy,3 H. Li,2 K. Praveen,3
J. Walsh,4 J. Hawkes,1 M. Milliken,1 D. Goldgar,1,2
J. Reid,3 J. Overton,3 F. Dewey,3 C. Gonzaga-Jauregui,3 S. Guthery,5 K. Callis Duffin1 andG. Krueger11Department of Dermatology, 2Huntsman Cancer Institute, 4Department of
Rheumatology and 5Department of Pediatrics, University of Utah, Salt Lake
City, UT, U.S.A. and 3Regeneron Genetics Center, Regeneron Pharmaceuticals
Inc., Tarrytown, NY, U.S.A.Psoriasis is a complex multigenic disorder, with heritability
estimated to be 60–90%. Although several large-scale gen-
ome-wide association studies and linkage studies have been
performed, there is still a large proportion of the familial
relative risk not explained by the known loci. To search for
the missing heritability of psoriasis, we performed whole-
exome sequencing and array genotyping of 1133 patients
with psoriasis and 1176 healthy controls. Among the cases
of psoriasis there were 73 pedigrees ascertained through a
genealogy database of 8 million individuals with up to 12-
generation pedigrees. We jointly analysed the pedigrees and
case–control samples by the framework PERCH, which quan-
titatively integrates the deleteriousness of variants, quality of
variant calls, cosegregation of variants with disease within
pedigrees, association of variants with disease among cases
or controls, and the connection of each gene with known
psoriasis genes within a gene–gene interaction network. The
results demonstrated several candidate genes for psoriasis,
but none of them reached genome-wide significance. To cre-
ate a homogeneous subset of samples, we then performed a
latent class analysis to identify groups of patients with simi-
lar clinical phenotypes. This analysis yielded three classes.
Class 3 was associated with a younger age of psoriasis initia-
tion, more severe disease, and trauma- or injury-associated
disease onset or worsening. Familial risk analysis further
showed that this class of patients had the highest level of
familial aggregation. Our second round of genomic analysis
restricted to this group of patients resulted in the identifica-
tion of ADAMTS9 with genome-wide significance
(P = 8 9 10�7), a locus that was previously reported to
have a higher deletion rate in psoriatic arthritis than in
healthy controls. Class 2 psoriasis showed a moderate familial
clustering and is not sensitive to sunlight treatment. Pedi-
gree-informed genomic analyses identified novel candidate
genes segregating in families. Network analysis further sug-
gested a role for some candidate genes in epithelial immune
response. These results highlight the importance of pheno-
typic classification of cases in a complex disease and the pos-
sibility that new susceptibility loci for psoriasis can be
discovered using a combination of family-based and cohort
approaches such as PERCH. They also suggest a new classifi-
cation scheme for psoriasis that is relevant to disease aetiol-
ogy and clinical management. The whole-exome sequencing
and array genotyping of psoriasis cases and healthy controls
were funded and performed by Regeneron Pharmaceuticals
Inc., Tarrytown, NY, U.S.A.
FC13Advances in genomic studies of psoriasis in ChinaX. Zhang1,21Institute of Dermatology, Anhui Medical University, Hefei, China and2Institute of Dermatology, Fudan University, Shanghai, ChinaPsoriasis is a complex polygenic disease caused by a number
of susceptibility genes. We have been engaged in the genetic
research of psoriasis. Here we consider our studies and review
the significant progress in genomic research into psoriasis in
China. In 2002 we performed a genome-wide scan in 61 mul-
tiplex families showing that chromosomes 6p21 (PSORS1) and
4q31 may contain genes involved in the susceptibility to pso-
riasis vulgaris in the Chinese Han population. The OMIM data-
base included 4q31-q34, named as PSORS9. In the following
study, human leucocyte antigen (HLA)-C was identified as the
susceptibility gene within the PSORS1 locus by fine mapping
and association analysis. In 2009 we reported the first gen-
ome-wide association study (GWAS) in 6860 cases and 8472
controls in the Chinese population; we identified a new sus-
ceptibility locus for psoriasis within the late cornified envelope
gene cluster. Subsequently, we extended our GWAS with a
multistage replication study in 11 425 cases and 17 107 con-
trols and identified six new susceptibility loci. In addition, we
presented the largest transethnic genome-wide meta-analysis
of psoriasis in 15 369 cases and 19 517 controls and identi-
fied four novel associations with psoriasis. In 2010 we coop-
erated with the Beijing Genomics Institute and first carried out
exome sequencing and targeted sequencing of psoriasis in
10 727 cases and 10 528 controls. Seven common and low-
frequency nonsynonymous single-nucleotide variants were
identified within known psoriasis susceptibility genes that
were associated with psoriasis risk. In order to investigate the
coding variants in psoriasis systematically, an exome-wide
association study in 42 760 individuals was first carried out
using exome array in 2015. Sixteen coding variants were sig-
nificantly associated with psoriasis, and these findings high-
light the genetic contributions of common coding variants to
the pathogenesis of psoriasis. In 2016 we carried out a com-
prehensive analysis of genetic variation in the major histocom-
patibility complex (MHC) region by directly sequencing the
whole region in 20 635 individuals of Han Chinese ancestry
and constructed a reference panel of the MHC variants (Han-
MHC database) for imputation. We further identified multiple
independent new susceptibility loci in HLA-C, HLA-B, HLA-
DPB1, BTNL2 and rs118179173 associated with psoriasis. We
performed a three-stage epigenome-wide association study in
262 skin and 48 peripheral blood mononuclear cell samples.
This study not only revealed genome-wide methylation pat-
terns for psoriasis but also identified strong associations
between the skin-specific DNA methylation of nine disease-
associated differentially methylated sites and psoriasis. Based
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
6 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
65ABSTRACTS
on 15 years of hard work, there have been great advances and
tremendous achievements in genetic research of psoriasis in
Chinese Han population. So far, more than 40 robust suscepti-
bility loci have been identified and confirmed to be associated
with psoriasis in the Chinese Han population. These genetic
loci may help to build the foundation for genetic diagnosis
and personalized treatment for patients with psoriasis in the
near future. However, substantial additional studies, including
functional and gene-targeted studies, are required to confirm
the causality of the genetic variants and their biological rele-
vance in psoriasis development.
FC14iRhom2: a mechanistic hub in keratinocytehyperproliferation and psoriasis?M. Brooke,1 T. Maruthappu,2 A. Chikh1 andD. Kelsell11Blizard Institute, Barts & The London School of Medicine & Dentistry,
London, U.K. and 2St John’s Institute of Dermatology, Guy’s and St Thomas’
NHS Trust, London, U.K.iRhom2 is a proteolytically inactive member of the rhomboid
family of intramembrane proteases, with recently emerging
key functions in epidermal homeostasis. We and others have
shown that iRhom2 mediates the maturation of the broad-
spectrum sheddase enzyme ADAM17, the protease solely
responsible for the cleavage and release of soluble cytokines
including tumour necrosis factor (TNF)-a and multiple
ligands of epidermal growth factor receptor (EGFR; including
amphiregulin and TGF-a). Subsequently, we have also
described a unique role for iRhom2 as a key regulator of the
hyperproliferation-associated keratin 16. The enormous suc-
cess of TNF-a inhibition in psoriasis treatment, in addition to
the established role of iRhom2/ADAM17 substrates in the
development of psoriatic plaques, and the upregulation of ker-
atin 16 in lesional psoriatic skin, therefore point to a hitherto
unidentified role for iRhom2 in psoriasis. In support of this,
we have shown that gain-of-function iRhom2 mutations result
in elevated shedding of TNF-a and EGFR ligands, hyperactive
EGFR signalling and keratin 16 upregulation, features of an
aberrant wound healing phenotype and hyperproliferative epi-
dermis. Conversely, although Irhom2 knockout mice appear
phenotypically normal at birth and in adulthood, we have
found that they develop significantly thinner paw epidermis
relative to controls, with barely detectable keratin 16 expres-
sion. Matching these data, we have shown that short hairpin
hRNA knockdown of iRhom2 in hyperproliferative ker-
atinocytes placed in three-dimensional organotypic culture
results in the generation of thinner epidermal equivalents.
Additionally, it has been shown that the Irhom2 knockout
mouse exhibits reduced inflammatory responses to infectious
stimuli and appears to be protected from developing another
TNF-a-driven disease, rheumatoid arthritis, in a transgenic
model. We have identified that iRhom2, ADAM17, TNF-a and
EGFR ligands are significantly upregulated at the mRNA level
in lesional psoriatic epidermis relative to nonlesional skin.
Intriguingly, we have also observed by immunofluorescence
that iRhom2 localization in human lesional psoriasis skin dif-
fers from that of controls. iRhom1, a relative of iRhom2, is
also capable of regulating ADAM17, but incapable of keratin
16 regulation. However, iRhom1 appears to regulate a low
level of ADAM17 activity in basal keratinocytes only, and
unlike iRhom2 it is not upregulated in lesional psoriasis. As a
consequence, therapeutic targeting of iRhom2 would allow
for the inhibition of excessive, disease-associated ADAM17-
dependent shedding, without affecting the relatively lower
iRhom1-dependent activity important for normal skin home-
ostasis. Therefore, as psoriasis shares several disease mecha-
nisms with those seen as consequences of iRhom2
hyperactivity, targeting iRhom2 in psoriasis represents an
attractive strategy.
FC15Identifying chromatin interactions betweenpsoriasis-associated variants and target genesusing Capture Hi-CH. Ray-Jones,1,2 A. McGovern,1 P. Martin,1 K. Duffus,1
S. Eyre1 and R.B. Warren1,2
1University of Manchester, Manchester, U.K. and 2Salford Royal NHS
Foundation Trust, Manchester, U.KGenome-wide association studies (GWASs) have identified
many risk loci for psoriasis, but most lead variants are outside
of protein-coding regions and therefore have an unknown
function. It is hypothesized that these variants regulate gene
function through DNA looping, whereby the variant is
brought into close contact with a distant gene promoter. To
identify putative gene targets, Capture Hi-C (CHi-C) can be
utilized. It is a cutting-edge chromosome conformation cap-
ture method that gives an unbiased view of chromatin interac-
tions in targeted regions of the genome. This work applied
CHi-C in psoriasis risk loci using relevant cell types and condi-
tions. CHi-C libraries were generated in duplicate using rele-
vant cell lines: MyLa (CD8+ T cells) and HaCaT
(keratinocytes). Two libraries were also generated from HaCaT
cells stimulated with interferon IFN)-c. RNA capture baits
were designed to target all known psoriasis-associated GWAS
loci; each locus was defined by a set of variants in linkage dis-
equilibrium with the lead GWAS variant (r2 > 0.8). The
libraries underwent next-generation sequencing generating
75-bp paired ends. The sequences were analysed using the
bioinformatics pipelines HiCUP and CHiCAGO. Chromatin
interaction data were obtained for psoriasis risk loci across the
genome represented by 107 lead GWAS variants (59 in Euro-
pean cohorts, 42 in Chinese and four in both populations).
There were 13 393, 6737 and 6956 significant interactions in
MyLa, unstimulated HaCaT and stimulated HaCaT cells, respec-
tively (CHiCAGO score > 5). In approximately 25% of cases,
the interactions overlapped with gene promoter regions
defined by fragments within 500 bp of a transcription start
site, corresponding to 1075 genes and noncoding RNAs in
total. This implicated gene targets in several loci; for example
NFKBIZ in 3q12.3 and KLF4 in 9q31.2. In some loci, the
potential target gene was narrowed down from a list of
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 7
compelling candidates. For example, the 1p36.23 locus har-
bours several likely genes including TNFRSF9, ERRFI1 and
SLC45A1. In HaCaT cells the psoriasis-associated variation inter-
acted with the promoter of ERRFI1, a gene encoding a protein
that inhibits epidermal growth factor receptor signalling and
is thought to be required for normal keratinocyte prolifera-
tion. In conclusion, this is the first use of CHi-C across all
psoriasis risk loci, demonstrating how intergenic variation
may contribute towards the pathogenicity of psoriasis. The tar-
get genes identified in these loci are candidates for down-
stream functional investigation as potential therapeutic targets
in psoriasis.
FC16The psoriasis-associated Act1(D10N) variantreduces responses to interleukin-17 but enhancesT helper 17 responses to polyclonal activationS. Lambert,1 C. Hambro,1 A. Johnston,1 R. Nair1 andJ. Elder1,21University of Michigan, Ann Arbor, MI, U.S.A. and 2Ann Arbor VA
Hospital, Ann Arbor, MI, U.S.A.Act1/TRAF3IP2 links the interleukin (IL)-17 receptor to down-
stream pathways. The TRAF3IP2 gene resides in a psoriasis sus-
ceptibility locus, with the single-nucleotide polymorphism
rs33980500, D>N in position 10 of Act1 increasing risk. In
order to investigate the effect of the Act1 D10N variant on IL-
17 signalling, we isolated keratinocytes, fibroblasts and
peripheral blood mononuclear cells (PBMCs) from individuals
homozygous for the common allele (wild-type, n = 9) or the
risk variant (D10N, n = 5). We found that both keratinocytes
and fibroblasts from Act1 D10N homozygotes displayed atten-
uated responses to IL-17 stimulation. Upon IL-17 stimulation
(100 ng mL�1, 3 h), fibroblasts from Act1 D10N homozy-
gotes had reduced mRNA expression of IL1A (46.4 � 3.6% of
wild-type, P = 0.04) and CCL7 (33.2 � 4.8% of wild-type,
P = 0.01). Keratinocytes from Act1 D10N homozygotes had
lower mRNA induction of CCL20 (20.9 � 4.4% of wild-type,
P = 0.04), DEFB4 (47.5 � 27% of wild-type, P = 0.013), and
IL36G (36 � 7.6% of wild-type, P = 0.023). We induced T
helper (Th)17 differentiation by CD3/CD28 bead stimulation
of PBMCs for 7 days in the presence or absence of neutrophil
extracellular traps (NETs), with further activation by phorbol
myristate acetate and ionomycin (P/I) for the final 6 h or
24 h. Under these conditions, we found that Ac1 D10N
homozygotes were significantly more responsive than wild-
type cells, with a fivefold increase in IL-17 elaboration by
enzyme-linked immunosorbent assay (19.1 � 3.7 ng mL�1
vs. 3.4 � 1.9 after 24 h of P/I treatment; n = 2). Act1 D10N
homozygotes also manifested increased IL-17A and IL-17F
mRNAs (3.2 and 3.5-fold vs. wild-type, respectively, after 6 h
of P/I treatment). Notably, these differences were observed
only in the presence of NETs. These results suggest that
despite reducing target cell responses to IL-17 stimulation, the
psoriasis-associated Act1 D10N variant increases Th17 differ-
entiation and/or responsiveness to polyclonal stimulation,
consistently with the genetic evidence implicating it as a pso-
riasis risk variant.
FC17ERAP1 risk variants in psoriasis vulgaris affectautoantigen presentationA. Arakawa,1 S. Vollmer,1 E. Reeves,2 E. James2 andJ.C. Prinz11Ludwig-Maximilians-University, M€unich, Germany and 2Southampton
General Hospital, Southampton, U.K.Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims the
NH2-terminus of antigenic peptide precursors to the appropri-
ate length for binding to and presentation by human leucocyte
antigen (HLA)-class I molecules to the T-cell antigen receptors
(TCRs) of T cells. ERAP1 polymorphisms result in different
peptide trimming specificities and activities. In various
autoimmune diseases ERAP1 variants display gene–gene inter-
actions with the predisposing HLA class I risk alleles. Psoriasis
vulgaris is an HLA-C*06:02-associated autoimmune disease. In
psoriasis, HLA-C*06:02 mediates an autoimmune response
against melanocytes through autoantigen presentation. Epistasis
between HLA-C*06:02 and ERAP1 variants affects the risk for
psoriasis, but the mechanisms of this gene interaction
remained unknown. We have used an HLA-C*06:02-presentedmelanocyte autoantigen, ADAMTS-like protein 5 (ADAMTSL5),
and an ADAMTSL5-specific Va3S1/Vb13S1 TCR from patho-
genic psoriatic CD8+ T cells to determine the role of ERAP1
variants in disease risk. Our data show that ERAP1 variants
increasing psoriasis risk were highly effective in generating
the antigenic ADAMTSL5 peptide from NH2-terminally elon-
gated ADAMTSL5 peptide precursors. Instead, a protective
ERAP1 variant reduced the availability of the antigenic
ADAMTSL5 peptide presumably through overtrimming and
peptide destruction. Several other peptide ligands from natural
human proteins that were recognized by the Va3S1/Vb13S1TCR due to TCR polyspecificity were not processed from pep-
tide precursors into antigenic peptides of appropriate length
for HLA binding and presentation. Thus, using a proven psori-
atic autoantigen from melanocytes and a pathogenic psoriatic
TCR, these experiments provide direct evidence of how differ-
ent ERAP1 variants can affect the risk of autoimmunity in pso-
riasis through differential trimming of a peptide autoantigen.
They furthermore demonstrate that the potential antigenicity
of self-peptides depends on ERAP1 trimming and indicate that
different ERAP1 affinities for different amino acid sequences
of precursor peptides finally determine autoantigens in CD8+
T-cell-mediated autoimmune diseases.
FC18Tumour necrosis factor blockade induces adysregulated type I interferon response withoutautoimmunity in paradoxical psoriasisC. Conrad,1 J. Di Domizio,1 A. Mylonas,1 O. Demaria,1
C. Belkhodja,1 A. Navarini,2 A.-K. Lapointe,1
L. French,2 M. Vernez1 and M. Gillliet1
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
8 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
67ABSTRACTS
1Department of Dermatology, University Hospital CHUV, Lausanne,
Switzerland and 2Department of Dermatology, University Hospital of Zurich,
Zurich, SwitzerlandAntitumour necrosis factor (anti-TNF) agents are highly effec-
tive in the treatment of psoriasis. However, in 2–5% of treated
patients they induce psoriasis-like skin lesions called paradoxi-
cal psoriasis. The pathogenesis of this side-effect and its dis-
tinction from classical psoriasis remain largely unknown. Here
we performed a comprehensive clinical, histological and gene
expression analysis of skin lesions from 25 patients with para-
doxical psoriasis. Paradoxical psoriasis is characterized by a
selective, uniform increase in type I interferon expression and
plasmacytoid dendritic cell (pDC) accumulation, despite
marked clinical and histological variations. Anti-TNF agents
stimulates pDCs to produce exaggerated levels of type I inter-
feron by inhibiting TNF-mediated pDC maturation both in vitro
and in a skin injury mouse model. Via type I interferon,
anti-TNF agents induce a psoriatic skin phenotype reflecting
paradoxical psoriasis, which is, unlike classical psoriasis, inde-
pendent of T cells. These findings indicate that paradoxical
psoriasis represents an overactive innate inflammation driven
by pDC-derived type I interferon; however, this is self-con-
tained as it does not lead to T-cell autoimmunity.
FC19Activation of resident T cells in resolved psoriasisreveals tissue responses that stratify clinicaloutcomeI.G. Serezal, C. Classon, S. Nyl�en, N.X. Land�en,E. Martini, S. Cheuk and L. EidsmoKarolinska Institutet, Stockholm, SwedenPathological resident memory T (TRM) cells poised towards
interleukin (IL)-17 production are enriched in resolved psoria-
sis, a focal inflammatory disease that often relapses in fixed
sites of the skin. To investigate the impact of resident T cells
on their immediate microenvironment, skin explants were
stimulated ex vivo with OKT-3, a CD3-activating antibody.
Transcriptomic analyses with RNA sequencing and Nanostring
revealed that T-cell activation resulted in upregulation of the
interferon-c-induced chemokine genes CXCL10 and CXCL9 in
healthy, active and resolved psoriasis. In contrast, IL-17-related
DEFB2 and genes involved in keratinocyte differentiation
(SPRR2 family) were selectively induced in both active and
resolved psoriasis, indicating that pathogenic TRM cells affect
tissue homeostasis in resolved psoriasis. An integrative analysis
of the response patterns to T-cell activation highlighted that
the balance between IL17 or DEFB2 and CXCL10 correlated to
the time to clinical relapse in patients after ultraviolet B treat-
ment, at both the RNA and protein levels. Our data show that
skin T cells induce clinically relevant tissue responses, with
the potential locally to steer focal pathology in psoriasis. Strati-
fication of such responses may be used to predict disease out-
come in resolved psoriatic skin.
FC20Longitudinal follow-up of arterial structure andfunction in patients with severe psoriasis treatedby anti-interleukin (IL)-12/IL-23 agents comparedwith tumour necrosis factor inhibitorsM. Viguier,1 H. Khettab,2 I. Hamdidouche,2
P. Boutouyrie2 and H. Bachelez31Dermatology Department, CHU Robert Debr�e, Reims, France; 2Pharmacology
department, Hopital Europ�een Georges Pompidou, INSERM U970, Paris,
France and 3Dermatology Department, Hopital Saint-Louis, INSERM UMR
1163, Institut Imagine, Paris, FrancePatients with chronic severe plaque psoriasis are at increased
cardiovascular risk. As the respective impacts of biological
therapy for psoriasis with TNF inhibitors (TNFis) and anti-
interleukin (IL)-12/IL-23 agents (ustekinumab) on cardiovas-
cular atherosclerotic disease are still debated, we launched a
single-centre parallel-group study aiming to characterize large
artery remodelling and stiffness during longitudinal follow-up
under any of the three approved TNFis (adalimumab, etaner-
cept, infliximab) and anti-IL-12/23. For this, we consecutively
included 31 patients with psoriasis starting treatment with
TNFis or anti-IL12/23 agents. Patients had to require systemic
biotherapies to control their psoriasis and have at least one
additional cardiovascular risk. Measurement of arterial struc-
ture and function was assessed blindly with respect to biolog-
ics at baseline and during treatment. The assessed parameters
were the following: diameter, intima media thickness (IMT)
and stiffness of the two carotids (echotracking); carotid pulse
wave velocity (PWV), carotid-to-femoral PWV and central
pressure (applanation tonometry). These were analysed using
mixed models. Patients were treated with either a TNFi
(n = 13) or an anti-IL-12/23 agent (n = 18). The male-to-
female sex ratio was 1.2 and the mean age was 49.8 years;
87% were overweight or obese, 55% were smokers, 32% had
controlled arterial hypertension, 23% had a personal or family
history of cardiovascular events and 13% had diabetes. The
patients did not differ according to baseline characteristics,
except for more frequent statin use in the anti-IL12/23 group
(28% vs. 0%). The mean follow-up was 13 � 3 months with
a mean number of three measurements. Carotid diameter did
not change significantly during follow-up. IMT increased more
with anti-IL12/23 than TNFis (Δ + 75 lm, P = 0.10). Carotid
distension and carotid distensibility decreased significantly
under anti-IL12/23, whereas it increased with a TNFi, inde-
pendently of blood pressure (Δ �3.82 kPa, P < 0.035). Caro-
tid PWV and carotid-to-femoral PWV increased independently
of blood pressure with anti-IL12/23 and decreased with TNFi
(Δ +1.15 m s�1, P < 0.05; + 1.60 m s�1, P < 0.03, respec-
tively). The increased arterial stiffness and the hypertrophy of
large arteries during longitudinal follow-up of patients under
ustekinumab in comparison with those receiving TNFis sup-
port differential impacts of these two classes of biologics on
arterial remodelling. Whether this is due to a protective effect
of TNFis and/or opposite effect of anti-IL12/23 remains to be
determined.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 9
FC21Real-world experience with apremilast in patientswith psoriasis: interim analysis of 104 patientsfrom the APPRECIATE studyE. Kleyn,1 M. Radtke,2 C. Bundy,3 K. Eyerich,4
M. St�ahle,5 M. Cordey,6 V. Koscielny,6
C.E.M. Griffiths7,8 and M. Augustin2
1The Dermatology Centre, The University of Manchester, Manchester, U.K.;2Institute for Health Services Research in Dermatology and Nursing,
University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3School
of Healthcare Sciences, University of Cardiff, Cardiff, U.K.; 4Department of
Dermatology and Allergy, Technical University of Munich, Munich,
Germany; 5Unit of Dermatology, Department of Medicine, Karolinska
Institutet, Stockholm, Sweden; 6Celgene International, Boudry, Switzerland;7The Dermatology Centre, Manchester, U.K. and 8The University of
Manchester, Manchester, U.K.Apremilast, an oral phosphodiesterase 4 inhibitor, is approved
for the treatment of adult patients with moderate-to-severe
plaque psoriasis and/or active psoriatic arthritis. This ongoing,
retrospective, cross-sectional combined study of patients with
psoriasis treated with apremilast, in a real-world setting, aims
to investigate patient characteristics, treatment outcomes and
benefits and limitations as perceived by patients and physicians
(NCT02740218). Presented here is a 6-month interim analysis
of results from 41 sites in Germany, Sweden and the U.K.
(42, 31 and 31 patients, respectively). Medical record review
(n = 104) showed that the patients’ mean age was 52.4 years
(median 53.0); 60 (57.7%) were female and mean time since
psoriasis diagnosis was 20.8 � 15.6 years. Common comor-
bidities included metabolic syndrome (22, 21.2%), psoriatic
arthritis (36, 34.6%) and obesity (11, 10.6%), and 91
(87.5%) had received at least one prior systemic or photother-
apy for psoriasis. At apremilast initiation, disease assessments
(mean � SD) included Psoriasis Area and Severity Index
(12.6 � 7.9), psoriasis-involved body surface area
(32.8 � 25.0%) and Dermatology Life Quality Index (DLQI)
score (12.8 � 7.3). For the Physician’s Global Assessment
(PGA) of disease activity, 69 patients (66.3%) had scores ≥ 3.
Reasons for initiating apremilast were ‘previous therapy was
ineffective’ (59.6%), ‘intolerant to previous therapy’ (26.0%),
‘contraindications to conventional therapies’ (7.7%) and
‘patient choice’ (3.9%). At 6 � 1 months’ follow-up, 74
(71.2%) patients continued to receive apremilast; 30 had dis-
continued due to lack of efficacy (n = 15, 14.4%), safety/tol-
erability (n = 11, 10.6%) or other reasons (n = 4, 3.9%).
Data available from patient charts showed that PASI 75 (≥75% reduction from baseline) was achieved by 20 of 52
patients (38%), 16 of 23 (70%) achieved ≥ 5-point improve-
ment on the DLQI, and 31 of 56 patients (55%) achieved a
PGA rating of 0 (clear) or 1 (almost clear). Based on these
assessments clinicians agreed or strongly agreed that apremilast
showed a rapid (62.5%) and sustained (54.8%) response, and
notably reduced plaque psoriasis (66.4%). Among patients
with the following symptoms at baseline, improvements were
reported with scalp (47 of 71, 66%), nail (24 of 42, 57%),
palmoplantar (18 of 26, 69%), nongenital inverse (20 of 28,
71%) and genital psoriasis (16 of 23, 70%), as well as pruri-
tus (49 of 67, 73%). Fifty patients (48.1%) reported at least
one adverse event. Adverse events were consistent with the
known safety profile of apremilast, including diarrhoea
(n = 20, 19.2%), nausea (n = 17, 16.3%) and headache
(n = 12, 11.5%). This interim analysis of a multinational real-
world study found meaningful improvements in physician-
assessed and patient-reported outcomes with apremilast ther-
apy in patients with psoriasis with a variety of disease mani-
festations and comorbidities. This study was funded by
Celgene Corporation.
FC22Topical methotrexate gold nanoparticles reduceimiquimod-induced inflammation in miceA. €Ozcan,1 D. Bunton,2 G. Macluskie,2 M. Duric,3
J. Barry3 and A. Kolios11University Hospital Zurich, Zurich, Switzerland; 2ReproCELL Europe Ltd,
Glasgow, U.K. and 3Midatech Pharma, Abingdon, U.K.Methotrexate (MTX) is a widely used immunosuppressive
agent for the treatment of several autoimmune and chronic
inflammatory conditions, such as rheumatoid arthritis and
psoriasis. MTX is usually administered systemically, which can
cause side-effects, including liver damage and kidney failure.
Due to its polarity and high molecular weight, topical MTX
penetrates very poorly through the skin barrier and therefore
needs a targeted drug delivery system to overcome biological
barriers. Gold nanoparticles (GNPs) have been used as a tar-
geted drug delivery system in cancer therapy and have
recently been shown to deliver MTX into the skin by topical
application. Here we explored the therapeutic potential of a
novel topical MTX formulation in inflammatory skin disease.
The skin permeability of MTX was increased via conjugation
to GNPs (MTX-GNP). Using the imiquimod-induced mouse
model of psoriasis, where imiquimod is applied on the ear of
a mouse, we evaluated the in vivo efficacy and functionality of
MTX-GNPs. Subcutaneous administration of MTX-GNPs ame-
liorated imiquimod-induced inflammation in a dose-depen-
dent manner, as measured by ear thickness, erythema and
scaling. Systemic MTX-GNP demonstrated a superior anti-
inflammatory action compared with systemic MTX on imiqui-
mod-induced inflammation. At day 5, the mean ear thickness
(MET) of the MTX-GNP treatment group was 286 lm,
whereas the MET of the MTX group was 335 lm. Compared
with the treatment group who received imiquimod only (MET
351 lm), the ear thickness of the MTX-GNP-treated mice was
significantly lower, but the effect of MTX alone was not
(P = 0.034 and P = 1.00, respectively). Additionally, MTX
treatment displayed higher toxicity than MTX-GNP. Topical
MTX-GNPs were formulated based on the systemic dose
inducing the highest clinical efficacy but the least toxicity.
Topical application of MTX-GNP gel significantly reduced imi-
quimod-induced inflammation on day 5, whereas a gel for-
mulation of MTX showed no improvement (MET of mice
treated with IMQ only: 390 lm; MET of MTX-GNP group:
288 lm, MET of MTX group: 346 lm; MTX-GNP vs.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
10 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
69ABSTRACTS
imiquimod only: P = 0.0025, MTX vs. IMQ only P = 0.38).
GNPs significantly improve delivery of MTX to the skin, thus
allowing transdermal application of the drug. Topical MTX-
GNPs reduced imiquimod-induced inflammation in mice
without significant toxicity. MTX-GNPs should be considered
as a nonsteroidal therapeutic option for inflammatory skin
diseases.
FC23Efficacy and safety of secukinumab in patients whohave failed antitumour necrosis factor-a treatmentfrom the U.K. and Republic of Ireland: results ofthe SIGNATURE studyR.B. Warren,1,2 J. Barker,3 D. Burden,4 A. Finlay,5
C. Hatchard,6 P. Jeffery,6 R. Williams6 andC.E.M. Griffiths1,21University of Manchester, Manchester, U.K.; 2Royal Salford NHS Foundation
Trust, Manchester, U.K.; 3St John’s Institute of Dermatology, London, U.K.;4Royal Infirmary of Edinburgh, Edinburgh, U.K.; 5Cardiff University School
of Medicine, Cardiff, U.K. and 6Novartis Pharmaceuticals U.K. Ltd, Frimley,
U.K.Secukinumab, a human anti-interleukin-17A monoclonal anti-
body, has been shown to be efficacious in the treatment of
moderate-to-severe plaque psoriasis, with a sustained effect
and a favourable safety profile. This open-label, noncompara-
tor study was designed to investigate the safety and efficacy of
secukinumab (300 mg and 150 mg) in patients with active
moderate-to-severe, chronic plaque psoriasis who had a prior
efficacy failure on antitumour necrosis factor-a biological
therapy, as defined by the National Institute for Health and
Care Excellence (NICE) criteria, in the U.K. and Republic of
Ireland population. In total 235 adults with moderate-to-
severe chronic plaque psoriasis from 53 sites received secuk-
inumab as subcutaneous injections of 300 mg or 150 mg for
a 16-week initiation period (weeks 0–4, 8, 12 and 16) fol-
lowed by two maintenance periods up to 72 weeks. There
were three subgroups: (i) inadequate response to first anti-
TNF-a therapy; (ii) adequate response after first anti-TNF-atherapy but subsequent loss of efficacy and (iii) failed more
than one anti-TNF-a therapy due to inadequate response. The
primary end point was the percentage of patients achieving
≥75% reduction in Psoriasis Area and Severity Index (PASI 75)
at 16 weeks. Key secondary outcomes included PASI 90 at
16 weeks. Safety was comprehensively assessed throughout
the study. The response rate for PASI 75 was 65.3% for
300 mg (95% confidence interval 52.4–76.7, P < 0.001) and
44.3% for 150 mg (95% confidence interval 31.8–57.5,P < 0.001). There was a statistically significant proportion of
PASI 75 responders at 16 weeks in all three subgroups for
300 mg, vs. a null hypothesis of > 20% placebo response
expected; however, only subgroup (ii) achieved statistical sig-
nificance in the 150-mg group. A Bonferroni correction was
applied to the primary and seven key secondary end points
resulting in two-sided hypothesis testing at the 0.625% level
and 99.375% confidence intervals. The PASI 90 response rate
at 16 weeks for 300 mg was 41.5%.The majority of adverse
events were mild to moderate in severity. The most com-
monly reported adverse events during the initiation period in
the 300-mg group were nasopharyngitis (16.9%), headache
(15.3%), oropharyngeal pain (11.0%) and nausea (11.0%).
Candida infection was reported in 4.2% of patients in the 300-
mg group in the first 16 weeks of treatment. The results of
this study provide reassurance of the real-world safety and
efficacy of secukinumab in this hard-to-treat patient popula-
tion with prior anti-TNF-a failure. This study was sponsored
by Novartis.
FC24The genetic analysis of a large pustular psoriasisresource highlights differential effects for IL36RNand AP1S3 mutationsS. Twelves,1 K. Farkas,2 S.E. Choon,3 D. Burden,4
C.E.M. Griffiths,5 A. Irvine,6 E. Tan,7 M. Szell,2
Z. Bata-Csorgo,2 C. Smith,1 F. Capon1 and J. Barker1
1King’s College London, London, U.K.; 2University of Szeged, Szeged,
Hungary; 3Hospital Sultanah Aminah, Johor Bahru, Malaysia; 4Royal
Infirmary of Edinburgh, Edinburgh, U.K.; 5University of Manchester,
Manchester, U.K.; 6Our Lady’s Children’s Hospital, Dublin, Ireland and7National Skin Centre, Singapore, SingaporePustular psoriasis is a rare autoinflammatory skin disease char-
acterized by the appearance of small sterile pustules, resulting
from the accumulation of neutrophils in the epidermis. The
disease can be further classified into three subtypes. General-
ized pustular psoriasis (GPP) is an acute condition, manifest-
ing with flares of widespread pustulation that may be
accompanied by systemic inflammation. Acrodermatitis con-
tinua of Hallopeau (ACH) and palmoplantar pustular psoriasis
(PPP) are chronic and localized diseases affecting the nail
apparatus (ACH) or the palms and/or soles (PPP). Mutations
in IL36RN and AP1S3 have been associated with a proportion
of cases of pustular psoriasis, but the rarity of the disease has
hindered attempts to study correlations between genotype and
phenotype. Here we have sought to address this issue through
the analysis of 400 affected individuals (210 GPP, 17 ACH
and 173 PPP), representing the largest cohort examined to
date. We found AP1S3 mutations only in patients of European
descent, where they accounted for 10.6% (22 of 207) of cases
of pustular psoriasis. AP1S3 alleles did not vary in frequency
among the various disease subtypes (P = 0.13), but displayed
a significant sex bias as 21 of 22 (96%) AP1S3-positive cases
were female (P= 0.032). This suggests that the penetrance of
AP1S3 mutations is modified by sex-dependent factors. IL36RN
alleles showed a less marked sex bias, with women accounting
for only 62% (38 of 61) of mutation carriers. In contrast, we
found that mutation rates were higher in GPP (22.9%, 48 of
210) and ACH (18%, three of 17) compared with PPP (6.5%,
10 of 154, P < 0.001). In conclusion, our findings indicate
that IL36RN alleles are most strongly associated with GPP,
while AP1S3 mutations confer a broader risk of pustular psori-
asis. The data also highlight PPP as the disease subtype that is
least understood at the genetic level, demonstrating the need
for further gene identification work.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 11
FC25Transcriptomic profiling of interleukin (IL)-36A,IL-36B and IL-36G cytokine responses inkeratinocytes demonstrates a high degree ofoverlap and dependency on MYD88 and nuclearfactor-kB signallingW. Swindell,1 M. Sarkar,1 M. Beamer,1 X. Xing,1
M. Kahlenberg,1 N. Ward,2 J. Voorhees,1 L. Tsoi,1
Y. Liang1 and J. Gudjonsson11University of Michigan, Ann Arbor, MI, U.S.A. and 2Case Western
University, Cleveland, OH, U.S.A.Interleukin (IL)-36 cytokines have recently emerged as key
proinflammatory cytokines in the pathogenesis of psoriasis,
particularly its pustular subtypes. However, little is known
about IL-36 downstream signalling and transcriptional
responses. The aim of this study was to elucidate transcrip-
tional responses downstream of the three IL-36 cytokines
(IL-36A, IL-36B and IL-36G) in keratinocytes using high-reso-
lution RNA sequencing. We identified between 788 and 1747
differentially expressed genes significantly altered by IL-1b, IL-36a, IL-36b or IL-36c cytokine stimulation following 8 or
24 h of treatment (10 ng mL�1, false discovery rate < 0.10,
fold change > 2.00 or < 0.05). There was strong correlation
between IL-36a, IL-36b and IL-36c and between IL-36 and
IL-1b responses at both 8 and 24 h. We identified a core set
of 225 differentially expressed genes common to the IL-1band IL-36 cytokines with similar early (8 h) and late (24 h)
responses. These were associated with leucocyte chemotaxis,
mucosal immunity and neutrophil activation. Genes induced
by IL-1b and IL-36 had prominent overlap with genes altered
in both plaque and pustular psoriasis (P = 3.9 9 10�14 and
P = 5.7 9 10�26, respectively). Furthermore, IL-1b/IL-36-increased differentially expressed genes overlapped
significantly (P < 10�5) with genes near known psoriasis
genome-wide association loci (e.g. TNFAIP3, ETS1, TNIP1 and
ZC3H12C). IL-1b and IL-36 induced expression of mRNAs
encoding the ligands IL1A, IL1B, IL36A, IL36B and IL36G,
demonstrating that these cytokines have the ability to regulate
their own expression positively. We also noted increased
expression of cathepsin S, which cleaves and activates IL-36
cytokines, along with elevated expression of proteins encoding
receptor subunits (IL1RAP) and downstream signalling ele-
ments (IRAK2, MYD88, TAB2). Transcription responses also
included negative feedback regulators, with increased expres-
sion of genes encoding receptor antagonists (IL1RN, IL36RN),
anti-inflammatory ligands (IL37, IL38) and a decoy receptor
(IL1R2). Both IL-1 and IL-36 responses were dependent upon
MYD88 signalling, as complete knockout of MYD88 by
CRISPR/Cas9 mutagenesis completely abrogated IL-36 sig-
nalling. Transcription factor analyses using a dictionary of
2934 motifs identified over-representation of motifs associated
with transcription factors from the ETS, SOX, GATA, JUN,
FOS and nuclear factor (NF)-jB families of transcription fac-
tors. These findings were validated by small interfering RNA
knockdown of ETS1 and NF-jB. These data provide the most
comprehensive assessment available of the effects of the IL-1
and IL-36 cytokines in keratinocytes. Our findings suggest that
the transcriptional responses of IL-1 and IL-36 rebalance IL-1/
IL-36 signalling through both positive and negative feedback.
Targeting IL-36 cytokine responses in keratinocytes may lead
to novel approaches to treat psoriasis and its clinical subtypes.
FC26Effectiveness, drug survival and safety of fumaricacid esters for moderate-to-severe psoriasis inroutine care: results from the German PsoriasisRegistry PsoBestM. Augustin,1 U. Mrowietz,2 M.A. Radtke,3 D. Thaci,4
K. Ralph,5 A. K€orber6 and K. Reich71Institute and German Center of Health Services Research in Dermatology,
University Medical Center of Hamburg, Hamburg, Germany; 2Department of
Dermatology, University of Kiel, Kiel, Germany; 3IVDP, University of
Hamburg, Hamburg, Germany; 4Department of Dermatology, University of
Schleswig-Holstein, L€ubeck, Germany; 5Dermatology Practice, Selters,
Germany; 6Department of Dermatology University of Essen, Essen, Germany
and 7Dermatologikum, Hamburg, GermanyFumaric acid esters (FAEs) are the most frequently prescribed
antipsoriatic systemic drugs in Germany. Currently, new com-
pounds of fumaric acid are licensed in Europe and North
America. Furthermore, FAEs are licensed globally for multiple
sclerosis. The study objective was the evaluation of effective-
ness, drug survival and safety of FAEs for psoriasis under rou-
tine care conditions in the German national registry PsoBest
compared with other nonbiological systemic drugs. The Ger-
man National Psoriasis Registry PsoBest evaluates the long-
term outcomes of patients receiving systemic antipsoriatic
treatments. To date, 824 dermatology private practices and
clinics are subscribed. It was founded in 2008 and more than
7000 patients have been recruited. For this analysis, patients
naive to the respective drugs (FAE vs. other systemics) were
observed for 12 months after first exposure. Adverse events
and serious adverse events were calculated as observed. In total
1318 patients reflecting 1807 patient-years (PY) on FAEs and
1302 control patients (2674 PY; 76.6% methotrexate, 17.4%
ciclosporin, 5.2% retinoids, 0.8% others) were included. The
mean age was 45.7 years (FAEs) and 48.9 years (controls);
40.6% (FAEs) and 41.7% (controls) were female. Patient
numbers at 3, 6 and 12 months were 785, 590 and 395 for
FAEs and 824, 610 and 365 for controls. For the FAE vs. con-
trol groups the mean treatment duration was 9.4 vs.
11.0 months, mean body mass index 28.0 vs. 28.5 kg m�2,
mean baseline Psoriasis Area and Severity Index (PASI) 13.9
vs. 14.2, mean Dermatology Life Quality Index (DLQI) 11.0
in both cohorts, and rate of psoriatic arthritis 5.2% vs. 24.7%.
Outcomes for the time points 3, 6 and 12 months were PASI
75, 25.0%, 47.8% and 54.2% for FAEs and 35.9%, 45.7% and
51.0% for controls; and DLQI 5.5, 3.8 and 3.0 for FAEs and
5.5, 4.3 and 3.7 for controls. There were no statistically sig-
nificant differences in serious adverse events; and no differ-
ences in adverse events except higher rates of gastrointestinal
infections (13.1 vs. 8.4 per 100 PY) and blood and lymphatic
disorders for FAEs (4.1 vs. 1.0 per 100 PY), and lower
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
12 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
71ABSTRACTS
infection rates for FAEs (3.0 vs. 6.0 per 100 PY and 8.4 vs.
13.1 per 100 PY). The median drug survival for FAEs was
54.8, compared with 51.1 months for other nonbiological
treatments (P = 0.40). Side-effects were the most frequent
reason for early discontinuation of FAEs. In conclusion, FAEs
in psoriasis routine treatment show markedly different base-
line profiles and distinct differences in adverse events, but
similar rates of serious adverse events, outcomes and drug sur-
vival in the first 12 months compared with other systemics.
FC27The lymphatic system plays an important role inthe migration of pathogenic T cells towardssynovial joints and entheses in psoriasisD. Verhaegh,1,2 E. Prens,3 A.M.C. Mus,2
P.S. Asmawidjaja,2 N. Davelaar,2 A. Hofman,4 J.-B. Jaquet,4 J.M.W. Hazes,2 M.R. Kok,1 E. Lubberts2
and R.J. Bisoendial1,21Department of Clinical Immunology and Rheumatology and 4Department of
Plastic Surgery, Maasstad Hospital, Rotterdam, the Netherlands and2Department of Rheumatology and 3Department of Dermatology, Erasmus
University Medical Center, Rotterdam, the NetherlandsPsoriasis is characterized by acanthosis, impaired immune cell
migration and remodelling of the vascular and lymphatic sys-
tem. Up to 30% of patients with psoriasis develop psoriatic
arthritis (PsA). The lymphatic system may control the migra-
tion of pathogenic T cells to either skin or synovial joints and
entheses. In this study human dermal lymphatic endothelial
cells (LECs; 0.5 9 104) and fibroblast-like synoviocytes of a
patient with PsA (PsA-FLS; 1.0 9 104) were preincubated for
3 days with media or PsA synovial fluid (PsA-SF; 20% v/v).
Then, LECs or PsA-FLS were cocultured with 2.5 9 104
CD4+ CD45RO+ CD25�/lo T cells that were sorted from
healthy donors with or without stimulation with aCD3/aCD28. After 72 h, T cells were immunophenotyped by flow
cytometry. Relevant T helper (Th) subsets were characterized,
including the CCR6+ subsets Th17.1 (CCR4� CXCR3+),
Th17/Th22 (CCR4+ CXCR3�), Th17 (CCR4+ CXCR3�
CCR10�) and Th22 (CCR4+ CXCR3� CCR10+). We also
looked at cutaneous lymphocyte-associated antigen (CLA), a
skin-homing receptor. Interleukin (IL)-17A, tumour necrosis
factor (TNF) and IL-22 protein levels in the cocultures were
determined by enzyme-linked immunosorbent assay. Stimula-
tion of CD4+ CD45RO+ T cells in coculture with PsA-FLS
skewed towards the CCR6+ subset Th17/Th22, which were
predominantly Th17 cells. Th17 differentiation was suppressed
in coculture with LECs even when LECs were activated upon
preincubation with PsA-SF. Stimulation of CD4+ CD45RO+ T
cells in coculture with LEC, as compared with PsA-FLS, pro-
moted the generation of the Th22 subset. Upon coculture,
activated LECs conserved CLA expression on stimulated
CD4+ CD45RO+ T cells at a higher level than PsA-FLS, partic-
ularly in the CCR6+ T-cell subset. In line with the fluores-
cence-activated cell sorting results, lower IL-17A levels and a
trend towards higher IL-22 levels were observed in the cocul-
tures with LEC, compared with the coculture with PsA-FLS.
No differences were seen for TNF protein levels. Further
investigation of the underlying mechanisms revealed an
important role for the lymphotoxin b receptor (LTbR) path-
way and the Notch ligand delta-like 4 during the coculture
experiments of the CD4+ CD45RO+ T cells with LECs. In con-
clusion, LECs are directly involved in T-cell differentiation and
homing capabilities, as shown by suppression of Th17 differ-
entiation in coculture experiments, compared with PsA-FLS.
Also, LECs promoted Th22 generation and conserved CLA
expression in CCR6+ T cells. The LTbR pathway and delta-like
4 may be involved in LEC-mediated modulation of T-cell
homing and deserve further exploration.
FC28Systemic inflammation and evidence of acardiosplenic axis in patients with psoriasisK.F. Hjuler,1 L.C. Gormsen,2 M.H. Vendelbo,2
A. Egeberg,3 J. Nielsen1 and L. Iversen1
1Department of Dermatology and 2Department of Nuclear Medicine and PET
Centre, Aarhus University Hospital, Aarhus, Denmark and 3Department of
Dermatology and Allergy, Herlev and Gentofte Hospital, University of
Copenhagen, Copenhagen, DenmarkPsoriasis has been associated with cardiovascular comorbidi-
ties, and a direct contribution from psoriatic inflammation
unrelated to traditional cardiovascular risk factors has been
suggested. Studies of soluble biomarkers of systemic inflam-
mation have shown evidence of mild systemic inflammation
in patients with psoriasis compared with healthy controls.
However, it is still not fully elucidated to what extent psoriasis
causes systemic inflammation, whether this is clinically rele-
vant, and whether this causally leads to premature cardiovas-
cular disease. Based on preclinical and cardiovascular clinical
data a central role of the spleen in the progression of
atherosclerotic disease has been suggested and conceptualized
as the ‘cardiosplenic axis’. Furthermore, it has been shown
that splenic inflammation assessed by 18F-fluorodeoxyglucose
(FDG) positron emission tomography (PET) computed
tomography (CT) is increased in patients with autoimmune
and inflammatory diseases, and that the splenic FDG uptake
correlates with measures of systemic inflammation. In this
observational, controlled clinical study we aimed to assess
splenic FDG uptake as a measure of systemic inflammation in
untreated patients with moderate-to-severe psoriasis compared
with retrospectively matched controls assessed by FDG-PET/
CT. A secondary objective was to investigate associations
between splenic activity and aortic and subcutaneous adipose
tissue inflammation. We included patients with moderate-to-
severe psoriasis (n = 12, mean age 61.4 � 4.1 years, 83%
men, mean Psoriasis Area Severity Index 14.5 � 4.3) and
matched controls (n = 23, age 60.4 � 4.5 years, 87% men).
Splenic inflammation was measured using the background-
corrected spleen liver ratio (SLR) based on mean standardized
uptake values. Aortic inflammation was previously assessed in
the patient cohort as the target-to-background ratio (TBR) of
the whole vessel. The mean SLR was increased in patients with
psoriasis compared with controls (mean SLR 0.94 � 0.11 vs.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 13
0.82 � 0.08, P= 0.001. A significant association between SLR
and aortic mean whole vessel TBR was found in patients with
psoriasis (Pearson r = 0.65, P= 0.02). A significant association
between SLR and subcutaneous adipose tissue inflammation
was also found in the population overall. Our data confirm
the existence of systemic inflammation in patients with psoria-
sis beyond that ascertained in previous biomarker studies, and
provide the rationale for a mechanistic link between psoriasis-
driven inflammation and cardiovascular comorbidity through a
spleen–atherosclerotic axis. The cardiosplenic axis may mecha-
nistically, at least in part, explain the epidemiological observa-
tion that patients with psoriasis have an increased risk of heart
disease.
FC29Efficacy and safety of risankizumab, an interleukin-23 inhibitor, in patients with moderate-to-severechronic plaque psoriasis: 16-week results from thephase III IMMhance trialA. Blauvelt,1 K.A. Papp,2 M. Gooderham,3,4
R.G. Langley,5 C. Leonardi,6 J.-P. Lacour,7 S. Philipp,8
S. Tyring,9 M. Bukhalo,10 J.J. Wu,11 J. Bagel,12
E.H. Frankel,13 D. Pariser,14 M. Flack,15 J. Scherer,15
Z. Geng,16 Y. Gu,16 A. Camez17 andE.H.Z. Thompson181Oregon Medical Research Center, Portland, OR, U.S.A.; 2K Papp Clinical
Research and Probity Medical Research, Waterloo, ON, Canada; 3School of
Medicine, Queen’s University, Kingston, ON, Canada; 4Centre for
Dermatology and Probity Medical Research, Peterborough, ON, Canada;5Dalhousie University, Halifax, NS, Canada; 6St Louis University, St Louis,
MO, U.S.A.; 7Hopital de l’Archet, University of Nice–Sophia Antipolis,Nice, France; 8Charit�e Universit€atsmedizin Berlin, Berlin, Germany;9University of Texas Health Science Center and Center for Clinical Studies,
Houston, TX, U.S.A.; 10Altman Dermatology Associates, Arlington Heights,
IL, U.S.A.; 11Kaiser Permanente Los Angeles Medical Center, Los Angeles,
CA, U.S.A.; 12Psoriasis Treatment Center of Central New Jersey, East
Windsor, NJ, U.S.A.; 13RISkinDoc, Cranston, RI, U.S.A.; 14Eastern Virginia
Medical School and Virginia Clinical Research Inc., Norfolk, VA, U.S.A.;15Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, U.S.A.,16AbbVie Inc., North Chicago, IL, U.S.A.; 17AbbVie Deutschland GmbH &
Co KG, Ludwigshafen, Germany and 18AbbVie Inc., Redwood City, CA,
U.S.A.Interleukin (IL)-23, a key regulator of multiple effector cyto-
kines [including IL-17, IL-22 and tumour necrosis factor
(TNF)], is thought to drive the development and maintenance
of psoriatic lesions. Risankizumab is a potent humanized IgG1
monoclonal antibody that inhibits IL-23 by specifically bind-
ing its p19 subunit. In a phase II trial, the efficacy and safety
of risankizumab were compared with those of ustekinumab,
an IL-12/IL-23 inhibitor, in patients with moderate-to-severe
chronic plaque psoriasis (Papp KA, Blauvelt A, Bukhalo M et al.
Risankizumab versus ustekinumab for moderate-to-severe pla-
que psoriasis. N Engl J Med 2017; 376: 1551–60). The primary
end point of ≥ 90% improvement in Psoriasis Rea and Severity
Index (PASI 90) at week 12 was achieved by a significantly
higher proportion of patients receiving risankizumab (77%,
pooled 90 + 180 mg doses) compared with ustekinumab
(40%). In addition, adverse events were similar between the
risankizumab and ustekinumab groups through week 48, sug-
gesting a comparable safety profile. Currently, multiple phase
III studies are in progress to investigate the efficacy and safety
of risankizumab in patients with moderate-to-severe chronic
plaque psoriasis. IMMhance (NCT02672852) is a phase III
multicentre, randomized, double-blind, placebo-controlled
trial evaluating the efficacy and safety of risankizumab vs. pla-
cebo in patients with moderate-to-severe chronic plaque psori-
asis. The initial 16-week placebo-controlled period was
followed by randomized withdrawal and subsequent re-treat-
ment with risankizumab. Randomization was stratified by
weight and prior TNF inhibitor exposure. The coprimary end
points were percentages of patients achieving PASI 90 and sta-
tic Physician’s Global Assessment 0 or 1 at week 16; missing
data were imputed as nonresponders. At baseline, 507 patients
at 60 sites were randomized 4 : 1 to receive either risankizu-
mab (150 mg at weeks 0 and 4) or placebo during the 16-
week placebo-controlled period. Baseline demographics and
disease characteristics from a preliminary analysis of the study
database are presented here. The mean age was 49.2 years and
mean weight was 92.0 kg; 70.2% of patients were male. A
history of diagnosed or suspected psoriatic arthritis was
reported in 34.5% of patients, and prior TNF inhibitor therapy
was reported in 36.5% of patients. The mean baseline PASI
and body surface area were 20.1 and 26.1%, respectively. Effi-
cacy and safety data from the IMMhance trial through
16 weeks (not yet available at the time of abstract submission)
will be presented. The results from a phase III trial of risanki-
zumab in patients with moderate-to-severe chronic plaque
psoriasis will be publicly revealed for the first time.
FC30Quality of care and use of systemic drugs forpsoriasis in the past 12 years: results from a seriesof nationwide health care studies in GermanyM. Radtke,1 M. Augustin1 and K. Reich21Institute and German Center for Health Services Research in Dermatology,
University Medical Center, Hamburg, Germany and 2Dermatologikum,
Hamburg, GermanySince the intervention of the first biological drugs for psoriasis
in 2005, the landscape of psoriasis health care has markedly
changed in most countries. In particular, there has been a dra-
matic increase in the potential of reaching normal quality of
life and good health status in patients with moderate-to-severe
disease. Nevertheless, in most countries there persist discrep-
ancies between the guideline recommendations for psoriasis
treatment and real-world health care: many patients with high
needs do not yet get appropriate healthcare. In Germany, the
quality of health care for psoriasis was very critical in 2005.
Most patients lacked sufficient care and only a minor portion
received systemic drugs. In the meantime, a national psoriasis
programme has been conducted in order to improve the qual-
ity of psoriasis care, including development of an evidence-
based guideline, a consensus of treatment goals, the invention
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
14 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
73ABSTRACTS
of a ‘culture of measurement’ and consensus national goals
for psoriasis care. These measures were supported by the
establishment of 30 regional psoriasis networks involving
more than 800 dermatologists. The outcomes of this national
psoriasis programme are evaluated on a regular basis. The cur-
rent analysis shows the long-term results of the programme,
including the results of the very recent survey from 2017. All
surveys were based on random samples of dermatology prac-
tices and clinics across the country. In each survey in 2004,
2008, 2014 and 2017, between 120 and 150 centres were
nominated, and data from patients and dermatologists were
obtained from a minimum of 1500 patients per survey,
including psoriasis characteristics, Psoriasis Area and Severity
Index (PASI), Dermatology Life Quality Index (DLQI), patient
benefit index, patient satisfaction and current and previous
treatments. Between 2004 and 2017 there was a significant
increase in the proportion of patients reaching sufficient qual-
ity of health care from 34% to 79% (total n = 6323). The
mean PASI reduced from 11.4 to 7.4, DLQI reduced from 8.6
to 5.6, and the proportion of patients with severe disease
dropped from 17.8% to 8.6%. With respect to drug treatment,
there has been a significant annual increase in the drug vol-
umes for systemic treatments by about 24% per year, with
€348 million in 2010 to €761 million in 2015. Despite these
significant increases in the use of systemic drugs for psoriasis,
there remain large regional disparities, with some federal
states spending more than €6.00 per capita of population for
biologics in psoriasis compared with €0.90 in others. Besides
regional disparities, there are also severe differences in access
to modern drugs between patients referring to a dermatologist
(> 70% chance of guideline-compliant treatment) compared
with GPs (< 40%). In conclusion, there has been a marked
increase in the proportion of patients with psoriasis receiving
guideline-compliant care, in particular systemic treatments for
moderate-to-severe disease. Nevertheless, many patients are
still lacking access to treatments. The national conference on
psoriasis care has thus decided to reconfirm the national
healthcare goals for psoriasis in the next 5 years with higher
thresholds to reach.
FC31Efficacy and safety of mirikizumab (LY3074828) inthe treatment of moderate-to-severe plaquepsoriasis: results from a phase II studyK. Reich,1,2 R. Bissonnette,3 A. Menter,4
P. Klekotka,5 D. Patel,5 J. Li,5 J. Tuttle5 andK. Papp6,71Dermatologikum Hamburg, G€ottingen, Germany; 2Georg-August-University,
G€ottingen, Germany; 3Innovaderm Research, Montreal, QC, Canada;4Department of Dermatology, Baylor University Medical Center, Dallas, TX,
U.S.A.; 5Eli Lilly and Company, Indianapolis, IN, U.S.A.; 6Papp Clinical
Research, Waterloo, ON, Canada and 7Probity Medical Research, Waterloo,
ON, CanadaInterleukin (IL)-23 is a cytokine involved in the pathogenesis
of psoriasis. In this phase II (AMAF, NCT02899988), multi-
centre, randomized, double-blind, placebo-controlled trial, we
investigated the efficacy and safety of different dose groups of
mirikizumab (LY3074828), a p19-directed interleukin-23
antibody, in patients with moderate-to-severe plaque psoriasis.
Mirikizumab is the United States Adopted Name, pending final
approval by the World Health Organization. Adult patients
with moderate-to-severe psoriasis were randomized at a
1 : 1 : 1 : 1 ratio to receive placebo (n = 52) or mirikizumab
30 mg (n = 51), 100 mg (n = 51) or 300 mg (n = 51) at
weeks 0 and 8. The primary objective was to evaluate the
superiority of mirikizumab over placebo in achieving ≥ 90%
improvement in Psoriasis Area and Severity Index (PASI 90)
response at week 16. Additional secondary objectives included
evaluation of superiority of mirikizumab to placebo in achiev-
ing PASI 75 and PASI 100 at week 16. Comparisons were
done using logistic regression analysis with treatment, geo-
graphical region and previous biological therapy in the model.
Missing data were imputed as nonresponse. Only selected data
are presented to avoid a potential impact on the ongoing
blinded study. Baseline characteristics were generally well bal-
anced across treatment arms. The primary efficacy end point
at week 16 was met for each dose group with PASI 90
responses of 0%, 29.4% (P < 0.01), 58.8% (P < 0.001) and
66.7% (P < 0.001), respectively, for patients treated with pla-
cebo and mirikizumab 30 mg, 100 mg and 300 mg. PASI
75/100 responses at week 16 were 52.9% (P < 0.001)/
15.7% (P < 0.05), 78.4% (P < 0.001)/31.4% (P < 0.01) and
74.5 (P < 0.001)/31.4% (P < 0.01) for the mirikizumab
30 mg, 100 mg and 300 mg groups, respectively, compared
with 3.8%/0% for the placebo group. During the 16-week
induction period, two (1.0%) patients discontinued the study
due to adverse events. There were two (1.3%) serious adverse
events in mirikizumab-treated patients compared with one
(1.9%) in placebo-treated patients. In conclusion, the week 16
PASI responses were highest in the 100-mg and 300-mg
mirikizumab treatment arms. Responses in all mirikizumab
treatment arms were significantly higher than with placebo.
The overall frequency of adverse events was similar for mirik-
izumab- and placebo-treated patients.
FC32Certolizumab pegol for the treatment of patientswith moderate-to-severe chronic plaque psoriasis:an overview of three randomized controlled trialsA. Blauvelt,1 K. Reich,2 M. Lebwohl,3 D. Burge,4
C. Arendt,5 L. Peterson,6 J. Drew,4 R. Rolleri6 andA. Gottlieb71Oregon Medical Research Center, Portland, OR, U.S.A.; 2Dermatologikum
Hamburg and SCIderm Research Institute, Hamburg, Germany; 3Icahn School
of Medicine at Mount Sinai, New York, NY, U.S.A.; 4Dermira, Inc., Menlo
Park, CA, U.S.A., 5UCB Pharma, Brussels, Belgium; 6UCB BioSciences,
Inc., Raleigh, NC, U.S.A. and 7New York Medical College, Valhalla, NY,
U.S.A.Certolizumab pegol (CZP), the only PEGylated, Fc-free, anti-
TNF biologic, is currently under development for treatment of
psoriasis and has demonstrated promising results in phase II
trials. Three 144-week, phase III, multinational, randomized,
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 15
double-blinded trials of CZP in adults with moderate-to-severe
chronic plaque psoriasis are currently ongoing: CIMPASI-1
(NCT02326298) and CIMPASI-2 (NCT02326272) are replicate
placebo-controlled trials, and CIMPACT (NCT02346240) is an
active- and placebo-controlled trial. Pooled results for CZP vs.
placebo from the first 16 weeks of CIMPASI-1, CIMPASI-2 and
CIMPACT are reported here. Patients in all studies were aged
≥ 18 years and had moderate-to-severe chronic plaque psoria-
sis for ≥ 6 months, Psoriasis Area and Severity Index (PASI) ≥12, body surface area affected ≥ 10% and Physician’s Global
Assessment (PGA ≥ 3), and were candidates for systemic ther-
apy. Pooled end points (week 16) included PASI 75 (≥ 75%
reduction from baseline), PGA 0/1 (‘clear’ or ‘almost ‘clear’
with ≥ 2-category improvement) and PASI 90 response. Safety
for all three studies was examined via treatment-emergent
adverse event (TEAE) monitoring. In the combined studies,
342 patients were randomized to CZP 400 twice weekly
(Q2W), 351 to CZP 200 Q2W and 157 to placebo. Demo-
graphic and baseline disease characteristics were similar across
treatment groups, and most patients were in their mid-40s
(mean 45.7 years, median 46.0), white (94%) and male
(63.9%). At week 16, more CZP 400 mg- and CZP 200 mg-
treated patients vs. placebo-treated patients were PASI 75
responders (CZP 400 mg Q2W: 80.1%, CZP 200 mg Q2W:
74.5%, placebo: 7.5%; P < 0.001 for both), PGA 0/1 respon-
ders (CZP 400 mg Q2W: 63.7%, CZP 200 mg Q2W: 54.6%,
placebo: 2.8%; P < 0.001 for both) and PASI 90 responders
(CZP 400 mg Q2W: 52.2%; CZP 200 mg Q2W: 44.5%; pla-
cebo: 1.6%; P < 0.001 for both). TEAEs for both doses of CZP
were infrequent and consistent with the known safety profile
of CZP and anti-TNF therapy, and serious TEAEs and serious
infections and infestations were rare across treatment groups
(CZP 400 mg Q2W: 4.7% and 0.6%, respectively; CZP
200 mg Q2W: 1.4% and 0%; placebo: 4.5% and 0%). No
deaths were reported in any of the three studies through week
16. In the phase III programme, treatment with CZP 400 mg
Q2W and 200 mg Q2W were associated with statistically sig-
nificant, clinically meaningful improvements in moderate-to-
severe chronic psoriasis, including a PASI 75 responder rate of
> 80% in the CZP 400 mg Q2W group. This study was
funded by Dermira, Inc. Dermira and UCB are in a strategic
collaboration to evaluate the efficacy and safety of cer-
tolizumab pegol in the treatment of moderate-to-severe plaque
psoriasis. Medical writing support was provided by Prescott
Medical Communications Group (Chicago, IL). All costs
associated with development of this abstract were funded by
Dermira, Inc.
FC33Switching or restarting of tumour necrosis factor-ainhibitors after interruption under daily-lifeconditions: efficacy report from the AustrianPsoriasis Registry (PsoRA)P. Wolf,1 W. Weger,1 L. Richter,2 A. Mlynek,3
P. Sator,4 W. Saxinger,5 G. Ratzinger,6 C. K€olli,7
C. Painsi,8 C. Bangert,9 R. Tatarski,10
M. Sch€utz-Bergmayr,11 P. Ponholzer,12
F. Trautinger,13 R. Strohal,14 R. M€ullegger,7
M. Inzinger,1 R. Lichem,1 W. Salmhofer1 andF. Quehenberger11Medical University of Graz, Graz, Austria; 2State Hospital of Vienna
Rudolfstiftung, Vienna, Austria; 3Hospital of Elisabethinen, Linz, Austria;4Hospital of Hietzing, Vienna, Austria; 5Hospital of Wels-Grieskirchen,
Wels, Austria; 6Medical University of Innsbruck, Innsbruck, Austria; 7State
Hospital, Wiener Neustadt, Wiener Neustadt, Austria; 8State Hospital,
Klagenfurt, Klagenfurt, Austria; 9Medical University of Vienna, Vienna,
Austria; 10Paracelsus Private Medical University Salzburg, Salzburg, Austria;11Johannes Kepler University Linz, Linz, Austria; 12Donauspital, SMZ OST,
Vienna, Austria; 13Karl Landsteiner University of Health Sciences, St. P€olten,
Austria and 14Federal Academic Teaching Hospital, Feldkirch, Feldkirch,
AustriaWe were interested in investigating how well tumour necrosis
factor (TNF)-a inhibitors act after switching or restarting after
interruption under daily-life conditions. A data export by
2016 from the Austrian Psoriasis Registry (PsoRA) revealed
that 141 patients fulfilled the inclusion criteria for this analy-
sis: (i) TNF-a inhibitor treatment duration of 3 months or
longer, (ii) switch to another TNF-a inhibitor, (iii) treatment
interruption of 3 months or longer before restarting with the
same TNF-a inhibitor and (iv) availability of complete data to
perform the analysis. Response to treatment in the registry is
recorded in treatment categories: 1, CR (complete remission);
2, ≥ 90% improvement in Psoriasis Area and Severity Index
(PASI) 90; 3, PASI 75; 4, PASI 50 or 5, PASI < 50. Reasons
for treatment interruption, with a mean time of 6.4, 10.1 and
10.2 months for infliximab (IFX), adalimumab (ADA) and
etanercept (ETA), respectively, were due mainly to complete
remission, patient wish or other; reasons for switching were
primarily for ineffectiveness or loss of initial response. The
main switch/restart combinations were ETA>ADA n = 72,
ADA>ETA n = 20, ADA>ADA n = 12 and ETA>ETA n = 12.
The treatment response (measured in PASI reduction category)
improved by 0.97 (from 4.49 to 3.51; P < 0.001) in
ETA>ADA switchers and by 1.05 (from 4.10 to 3.05;
P = 0.035) in ADA>ETA switchers. Intriguingly, there was a
trend for loss of efficacy in the ADA>ADA restarters by �1.08
(from 1.58 to 2.67; P = 0.055), whereas in the ETA>ETArestarters efficacy was sustained (2.75 vs. 2.75, P = 1.0), com-
paring the outcome after the first treatment cycle vs. the sec-
ond cycle. For IFX, the case numbers of the groups of were
too low (n < 10) to be included in the statistical analysis.
These data generated under daily-life conditions are consistent
with the notion that after an initial unsatisfactory treatment
response, switching either from ETA to ADA or from ADA to
ETA can result in an improved treatment outcome. Moreover,
the data also support the concern that after treatment interrup-
tion, restarting with ADA (e.g. due to neutralizing antibodies)
but not with ETA may result in a weaker treatment response.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
16 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
75ABSTRACTS
Posters
P001Evaluation of serum uric acid among patients withpsoriasis in a developing countryS.D. Joshi1 and L. Limbu21Far Western Community Hospital, Attariya, Nepal and 2Sahid Memorial
Hospital, Kathmandu, NepalPsoriasis is a common chronic inflammatory skin disorder.
Studies have shown that psoriasis can progress to systemic
involvement such as in psoriatic arthritis, metabolic syn-
drome, and uric acid and lipid metabolism derangement. The
aim of this study was to evaluate serum uric acid levels
among patients with psoriasis. From the departments of der-
matology of two tertiary-care hospital in Kathmandu, 138
patients were enrolled in the study. Among them were 69
patients with psoriasis selected as cases, 36 male and 33
female; 69 patients with other dermatological diseases after
matching age and sex were selected as controls. After
informed written consent was received, a full detailed history
and physical examination was conducted, and determination
of the body mass index (BMI) and Psoriasis Area and Severity
Index (PASI) of cases was calculated. Serum samples of both
cases and controls were sent for uric acid investigation.
Chronic plaque psoriasis was the most common variant (60,
87%), and there was no significant association between psori-
asis type and sex. The male-to-female ratio was 1.1 : 1. The
majority of the patients with psoriasis (76%) were among the
younger population, and most of them (91%) had a normal
serum uric acid level. Most of the patients (55, 80%) did not
have a family history of psoriasis. Most patients (58, 84%)
had history of a flare-up in the winter season. BMI was found
to be in the normal range in most of the patients (65, 94%).
Among the control group, eczema was the most common
diagnosis (16, 23%), and most of the patients (91%) had
normal serum uric acid levels. No significant association
between PASI score and serum uric acid level was found in
the study (P = 0.81). Most of the patients had aggravation of
psoriasis in winter. However, serum uric acid was not signifi-
cantly associated with PASI, which may be due to psoriasis
lesions not being severe or, extensive body surface area
involvement and no systemic complication issues. However,
we have to rule out other systemic complications due to pso-
riasis in a long-term follow-up.
P002A transcriptomic study investigating thepathogenesis of generalized pustular psoriasisM. Catapano,1,2 F. Capon,1 F. Ciccarelli12 andJ. Barker11King’s College London, London, U.K. and 2The Francis Crick Institute,
London, U.K.
Generalized pustular psoriasis (GPP) is a rare form of psoriasis
manifesting with episodic flares of widespread skin pustulation
and systemic inflammation. Although the pathogenesis of GPP
remains poorly understood, genetic studies have identified
mutations in AP1S3, CARD14 and IL36RN, indicating an involve-
ment of innate, autoinflammatory pathways that appear to be
distinct from those causing psoriasis vulgaris. The aim of our
study was to investigate the molecular pathogenesis of GPP, as
well as its overlap with psoriasis and autoinflammatory dis-
eases. To achieve this purpose, we generated whole-blood
RNA sequencing data on nine cases of GPP cases and seven
sex- and age-matched controls. We also accessed publicly
available transcriptome datasets, relating to psoriasis or autoin-
flammatory syndromes mediated by interleukin-1 (cryopyrin-
associated periodic syndrome, CAPS) or type I interferon
(chronic atypical neutrophilic dermatosis with lipodystrophy
and elevated temperature, CANDLE). We analysed all expres-
sion profiles using DESeq2, limma and Ingenuity Pathway
Analysis. The analysis of the GPP whole-blood transcriptome
identified 86 genes that were upregulated in patients com-
pared with controls (fold-change 1.5, false discovery rate
< 0.05). These differentially expressed genes showed no sig-
nificant overlap with those that are overexpressed in psoriasis
(P = 0.057) or CAPS (P = 0.07). Conversely, the proportion
of upregulated genes shared between GPP and CANDLE was
highly significant (P = 3.2 9 10�7). Moreover, pathway
enrichment analysis of the 86 genes upregulated in GPP high-
lighted a strong type I interferon signature (false discovery
rate = 8.7 9 10�6). In keeping with this observation, the
combined expression of five key IFN-induced genes (IFI6,
IFIT3, IFITM3, OASL and PLSCR1) was higher in cases than in
controls (P < 0.05). In conclusion, our results confirm the
notion of abnormal innate immune regulation in GPP and
warrant further investigations of type I interferon signalling in
this disease.
P003Patient perception and the importance of clear/almost clear skin as a treatment goal in moderate-to-severe plaque psoriasis: results of the ‘Clearabout Psoriasis’ worldwide patient surveyA. Armstrong,1 S. Jarvis,2 W.-H. Boehncke,3
M. Rajagopalan,4 P. Fern�andez-Pe~nas,5 R. Romiti,6
A. Bewley,7 M. O’Donnell,8 L. Huneault,8 E. Dekker,8
M. Sodha9 and R.B. Warren10
1Department of Dermatology, University of Southern California, Los Angeles,
CA, U.S.A.; 2Richford Gate Medical Practice, London, U.K.; 3Division of
Dermatology and Venereology, Geneva University Hospital, and Department of
Pathology and Immunology, Faculty of Medicine, University of Geneva,
Geneva, Switzerland; 4Department of Dermatology, Apollo Hospitals, Chennai,
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 17
India; 5Department of Dermatology, Westmead Hospital, The University of
Sydney, Westmead, Australia; 6Department of Dermatology, Hospital das
Cl�ınicas University of S~ao Paulo, S~ao Paulo, Brazil; 7Whipps Cross
University Hospital and the Royal London Hospital, London, U.K.; 8Novartis
Pharma AG, Basel, Switzerland; 9GfK, Basel, Switzerland and 10The
Dermatology Centre, Salford Royal NHS Foundation Trust, The University of
Manchester, Manchester Academic Health Science Centre, Manchester, U.K.With the advent of new and increasingly effective therapies,
clear/almost clear skin is now recognized by dermatologists as
the optimal treatment standard in patients with psoriasis.
However, limited data exist on patient perception of the effi-
cacy of psoriasis therapies and whether clear/almost clear skin
is attainable. The ‘Clear about Psoriasis’ worldwide survey was
conducted in patients with moderate-to-severe plaque psoriasis
to assess patient perception of the disease in terms of treat-
ment satisfaction, clinical outcomes and the importance of
clear/almost clear skin. The survey was conducted from Octo-
ber 2015 to March 2016 in adult patients with moderate-to-
severe plaque psoriasis [self-reported Psoriasis Area and Sever-
ity Index (PASI) ≥ 10 or PASI 5–10 with impact of psoriasis
on sensitive/prominent body parts: face, palms, hands, fin-
gers, genitals, soles of feet or nails] from 31 countries in Asia,
Australia, Europe, North America and South America. Of 8338
patients included in the survey, the mean age was 44 years
and 55% were female. The majority of the patients were
employed (67%), married (55%) and had self-reported psori-
atic arthritis (51%). The mean self-reported PASI score was
14.3; 68% had PASI score ≥ 10 and 32% had PASI score 5–10. Overall, 56% of patients were satisfied with their current
treatment, 20% were dissatisfied and 24% were uncertain.
Most patients (57%, n = 4733) did not achieve clear/almost
clear skin with their current therapy; among them, 56% dis-
agreed that clear/almost clear skin was a realistic aspiration.
Among respondents who had achieved clear/almost clear skin
(43%, n = 3605) with their current treatment, 53% did not
believe that clear/almost clear skin was possible before actu-
ally achieving this goal. Furthermore, 73% of respondents
with self-reported clear/almost clear skin initiated their cur-
rent efficacious treatment > 1 year after diagnosis; of these
28% had to wait > 5 years. The majority of patients (84%)
experienced discrimination and/or humiliation due to psoria-
sis, 43% patients believed that psoriasis had affected their past
or current relationships, and 54% felt that psoriasis had
impacted their professional life. Among employed patients
(n = 5537), 42% needed ≥ 1 day off from work in the previ-
ous 6 months due to psoriasis, and 16% needed ≥ 10 days
off. Patients who had not achieved clear/almost clear skin
reported that such an achievement would open new possibili-
ties, like lying on a beach/sunbathing (59%), swimming
(58%) and a wider choice of clothing (40%). The ‘Clear
about Psoriasis’ survey highlights the importance of clear/al-
most clear skin to patients with psoriasis and the persistence
of inadequate treatment, even with the availability of effective
therapeutics. This study was sponsored by Novartis Pharma-
ceuticals.
P004Immunogenicity with tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, in a pooledanalysis of three randomized controlled trials inpatients with chronic plaque psoriasisA. Kimball,1 A. Blauvelt,2 K. Reich,3 Q. Li,4 F. vanAarle,4 T. Kerbusch5 and D. Montgomery4
1Harvard Medical School, Boston, MA, U.S.A.; 2Oregon Medical Research
Center, Portland, OR, U.S.A.; 3SCIderm Research Institute and
Dermatologikum Hamburg, Hamburg, Germany; 4Merck & Co, Inc.,
Kenilworth, NJ, U.S.A. and 5Certara U.S.A., Inc., Princeton, NJ, U.S.A.We evaluated antidrug antibody (ADA) development with til-
drakizumab, an anti-interleukin (IL)-23p19 monoclonal anti-
body in development for psoriasis, in 1400 patients pooled
from three randomized controlled studies: P05495 (phase IIb;
NCT01225731), reSURFACE 1 (phase III; NCT01722331) and
reSURFACE 2 (phase III; NCT01729754). Each study included
tildrakizumab 200-mg and 100-mg doses and had treatment
until week 52 (P05495 and reSURFACE 2) or week 64 (re-
SURFACE 1). Patients with at least one postdose ADA result
were evaluated. The proportions of treatment-emergent-
positive (TE-POS) patients to evaluable patients were reported.
TE-POS patients were further characterized for neutralizing
capacity (NAb-POS). The proportions of TE-POS patients were
4.3% (100 mg) and 4.1% (200 mg) through 12–16 weeks
(primary end points) and 6.5% (100 mg) and 8.2%
(200 mg) through 52–64 weeks. The proportions of TE-POS/
NAb-POS were 0.6% for both doses through 12–16 weeks
and were 2.5% (100 mg) and 3.2% (200 mg) through 52–64 weeks. The proportion of inconclusive patients through
52–64 weeks was low (< 7%), hence most of the remaining
dataset was reliable for interpretation. Patients in the TE-POS/
NAb-POS category showed decreased tildrakizumab concentra-
tions, and a modest increase in median clearance (36.5%) vs.
ADA-negative patients. The proportions of TE-POS (NAb-POS
and NAb-NEG) patients vs. negative/inconclusive patients
achieving ≥ 75% improvement in Psoriasis Area and Severity
Index (PASI 75) at week 12 were 60% vs. 63% (100 mg) and
69% vs. 65% (200 mg); for PGA clear or minimal at week 12
they were 57% vs. 58% (100 mg) and 66% vs. 60%
(200 mg). When the subgroup of TE-POS NAb-POS patients
was isolated and compared with ADA-negative patients
through week 12, percentage PASI improvements were 62%
(n = 4) vs. 75% (n = 603) for 100 mg and 38% (n = 4) vs.
76% (n = 374) for 200 mg. For patients on 100 mg or
200 mg continuously through week 52, the subgroup of TE-
POS NAb-POS patients was compared with ADA-negative
patients. This subgroup showed lower percentage improve-
ments vs. ADA-negative patients: 76% (n = 10) vs. 91%
(n = 342) for 100 mg and 77% (n = 12) vs. 87% (n = 299)
for 200 mg. Clinical responses in other ADA-positive cate-
gories and inconclusive patients were similar to those in nega-
tive patients. The incidences of adverse events and serious
adverse events were similar in the TE-POS and negative/incon-
clusive groups. In summary, ADA development in patients on
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
18 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
77ABSTRACTS
tildrakizumab over 52 weeks was low and had a minimal
impact on efficacy and safety.
P005Next-generation sequencing identifies epidermalmicroRNAs deregulated in psoriasis skinA. Srivastava,1 L. Pasquali,1 F. Meisgen,1
M. Stahle,1,2 N.X. Land�en,1 A. Pivarcsi1 andE. Sonkoly1,21Karolinska Institutet, Stockholm, Sweden and 2Karolinska University
Hospital, Stockholm, SwedenPsoriasis is a common chronic inflammatory skin disease,
which is thought to be a result of aberrant interaction
between keratinocytes and the immune system. MicroRNAs
(miRNAs) are short noncoding RNAs that regulate the expres-
sion of the majority of protein-coding genes. We and others
have previously identified miRNAs deregulated in psoriasis
skin, which regulate keratinocyte and/or immune cell func-
tions. Most of the previous studies utilized full-depth skin
biopsies, which contain a mixture of cells, and thus cell-speci-
fic transcriptomic changes may have been masked by expres-
sion in other cell types. Here we analysed the miRNome of
CD45 (nonimmune) sorted epidermal cells from lesional and
nonlesional skin of patients with psoriasis, and from healthy
skin of control patients by next-generation sequencing (RNA-
seq) of small RNAs. Our results revealed differential expres-
sion of 104 miRNAs in the epidermal cells in psoriasis
lesions, including several known and novel miRNAs that have
not been previously associated with psoriasis. MiR-149 was
identified as one of the significantly downregulated miRNAs,
and quantitative polymerase chain reaction analysis confirmed
its downregulation in psoriatic lesional epidermal cells com-
pared with those from nonlesional or normal skin. In primary
human keratinocytes and in three-dimensional epidermal
equivalents, miR-149 was significantly downregulated by
interferon (IFN)-c. Overexpression of miR-149 suppressed the
IFN-c-induced expression of interleukin-6, as well as T-cell-
attracting chemokines, while inhibition of endogenous mi
R-149 led to increased induction of these mediators. Taken
together, we have characterized the cell-specific miRNome in
epidermal nonimmune cells in psoriatic skin, and identified
epidermal miRNAs previously not associated with psoriasis.
MiR-149 has been identified as a miRNA regulating the
response of keratinocytes to IFN-c. Our results can provide a
basis for further functional studies of miRNAs in keratinocytes,
which might lead to identification of potential targets for topi-
cal therapy in psoriasis.
P006Effect of adipose-derived stem cells on animiquimod-induced psoriasiform mouse model byhypodermic injectionJ. Deng, C. Lu, L. Han and Y. HuangGuangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaOur study objective was to explore the effects of adipose-
derived stem cells (ADSCs) on an imiquimod-induced
psoriasiform mouse model by hypodermic injection. Mice
were topically painted with imiquimod for seven consecutive
days to develop psoriatic skin lesion. Mice in the experimental
group had hypodermic injection of ADSCs at day 3 and day 6,
while the control group were given a hypodermic injection of
normal saline. Various analyses related to lesion severity, ingu-
inal lymph nodes change and cytokines expression of lesions
were carried out. Compared with the control group, the Psori-
asis Area and Severity Index score was reduced in the experi-
mental group. Inguinal lymph nodes as the immune organ
were enlarged due to imiquimod painting in the control
group. However, the size of inguinal lymph nodes trended to
normal after ADSC injection. T helper (Th)1/Th2/Th17
cytokines in lesions were detected by flow cytometry. Com-
pared with the control group, the expressions of interferon-cand tumour necrosis factor-a were decreased after ADSC
injection. ADSC hypodermic injection can alleviate
imiquimod-induced psoriasiform lesions, and may exert
immune regulation effects by direct cell-to-cell contact.
P007Impairment of gustatory and olfactory senses inplaque psoriasisP. R€uter,1 V. Gr€unthaler,1 Y. Zopf2 andM. Sticherling11Hautklinik Universit€atsklinikum Erlangen, Erlangen, Germany and2Medizinische Klinik 1, Universit€atsklinikum Erlangen, Erlangen, GermanyThe various aspects of nutrition are a major issue in patient care
for psoriasis. Metabolic disorders and increased body mass index
are frequently encountered in this patients group and may result
from systemic inflammation characteristic for the disease and/
or unbalanced intake of food calories by the patients. Interest-
ingly, in chronic inflammatory bowel diseases relevant gustatory
and olfactory changes have been detected. These result in a dis-
turbed food intake and are normalized again upon successful
treatment of the disease. Here, patients with psoriasis were
tested before any systemic treatment for the gustatory qualities
sweet, sour, salty, bitter and umami. They were tested with
appropriate solutions sprayed onto the back of the tongue in a
standardized procedure, as well as by using sniffing sticks for
olfaction. Thirty-three patients were tested: 18 women and 15
men with a mean age of 54.3 years (range 21–85), a mean Pso-
riasis Area and Severity Index (PASI) of 8 (range 0.7–24) and
mean C-reactive protein (CRP) of 5.4 ng mL�1 (range 0.6–24.1). The results were compared with those in a group of
healthy volunteers. Whereas sweet taste was detected by all
patients, bitter could not be tasted by 21 patients and umami by
11 patients. Two and 23 patients showed hyposmia with results
off the 10% and 50% percentiles of normal volunteers, respec-
tively. Altogether, a distinct impairment of gustatory and olfac-
tory senses was found in patients with psoriasis. Considering
the low number of patients, the correlation to PASI and CRP was
barely significant. In addition, a normalization of sensory capac-
ity in relation to therapeutic responses and improvement of pso-
riasis has to be monitored.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 19
P008Psoriasis in children: a single-centre analysisF. Heppt, J. Raap and M. SticherlingDepartment of Dermatology, University Hospital of Erlangen, Erlangen,
GermanyEvidence-based guidelines for the treatment of psoriasis in
childhood are still lacking. Although several consensus recom-
mendations have been presented within the last few years,
treatment of paediatric psoriasis remains challenging for der-
matologists and paediatricians. The aim of this study was to
analyse more data regarding epidemiology, clinics, associated
comorbidities and therapeutic strategies. In a monocentric, ret-
rospective analysis over a period of 5 years (2009–2014), allpaediatric patients (age < 18 years) with psoriasis of any type
were evaluated. Diagnosis was usually made by the clinical
appearance and, if necessary, histologically confirmed.
Descriptive statistics were used for analysis. In total 73 patients
were analysed, representing 3.7% of all treated patients with
psoriasis in the analysis period. There was a female predomi-
nance (55%) and the mean age of disease onset was
10.5 years (range 2–17). Forty cases (45%) showed a positive
family history. The most common form was classic plaque
type psoriasis (67%), whereas the guttate form was seen in
30% of the patients. Five patients (7%) had psoriatic arthritis.
Specific topical treatments included corticosteroids (81%),
vitamin D analogues (73%), dithranol (32%) and calcineurin
inhibitors (8%). Fourteen patients received phototherapy and
systemic treatment was given in nine cases. Concerning the
most common comorbidities, six patients (8%) showed symp-
toms of a depressive mood. In addition, five children (7%)
were identified who had arterial hypertension and another five
were obese. In conclusion, regarding the high rate of comor-
bidities in our study population, screening for and manage-
ment of these comorbidities in this young and sensitive
population are of prime importance, especially concerning
long-term follow-up. International evidence-based guidelines
for the treatment of childhood psoriasis are highly desirable.
P009Interleukin-36c detection via noninvasive tapestripping reliably diagnoses psoriasisA. Keszegpal,1 A. Latzko,1 G. Brown,2 M. Goodfield,3
P. Laws,3 T. Macleod,4 J. Ainscough,4 A. Alase,1
D. Reid,2 J. Wenzel,5 P. Helliwell,1 M. Stacey4 andM. Wittmann1
1University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal
Medicine, Leeds, U.K.; 2University of Aberdeen, MRC Centre for Medical
Mycology, Aberdeen, U.K.; 3Department of Dermatology, Leeds, U.K.;4University of Leeds, School of Cellular and Molecular Biology, Leeds, U.K.
and 5University of Bonn, Department of Dermatology, Bonn, GermanyPsoriasis is a common skin disease that presents with a variety
of clinical phenotypes. In certain anatomical locations (e.g.
palmoplantar, auricular, intertriginous) or in cases of minimal
clinical activity, diagnosis can be problematic. In primary care
settings some psoriasis subtypes can be misdiagnosed as
eczema or other skin conditions. This study aimed to develop
a simple, reliable diagnostic tool for psoriatic inflammation.
Our approach was to use a noninvasive tape-stripping
methodology and enzyme-linked immunosorbent assay
(ELISA)-based measurement of cytokines including an in-
house-developed ELISA for interleukin (IL)-36c. Epidermal
cytokines from skin of healthy individuals were compared
with skin lesions typical for psoriasis or atopic dermatitis. We
here demonstrate that IL-36c is a highly sensitive and selective
protein biomarker that distinguishes psoriasis from eczema
lesions and is superior to other proteins upregulated in psori-
atic epidermis including IL-8, IL-18 and CXCL1. Receiver
operating characteristic curve analysis showed 90.6% sensitiv-
ity and 100% specificity at a cut-off level of 540 pg IL-36clg�1 total protein. In clinically ambiguous skin lesions requir-
ing diagnostic biopsies, IL-36c also proved to diagnose psori-
atic inflammation accurately. Epidermal markers that have
previously been linked to atopic eczema, including thymic
stromal lymphopoietin and CCL17, failed to show a robust
diagnostic potential in this approach. We conclude that pro-
tein sampling and detection of IL-36c via noninvasive tape-
stripping allows reliable diagnosis of psoriasis. This diagnos-
tic could improve patients’ outcomes by avoiding inappro-
priate treatment such as topical or systemic antibiotics,
which are often seen in primary care settings where lesions
may be confused with eczema. Correct identification of skin
psoriasis will facilitate early diagnosis of psoriatic arthritis
and prevention strategies for other psoriasis-associated
comorbidities.
P010Caffeine in the treatment of atopic dermatitis andpsoriasis: a reviewM. Alashqar1 and N. Goldstein21Alfaisal University, Riyadh, Saudi Arabia and 2Mount Sinai Health System,
New York, NY, U.S.A.Atopic dermatitis (AD) and psoriasis are inflammatory skin
diseases. AD is characterized by immune dysregulation and
barrier impairment, while psoriasis shows immune dysfunc-
tion and resultant keratinocyte hyperproliferation. Caffeine has
shown efficacy in ameliorating the symptoms of both diseases,
but it is not conclusive through which pathways. The aim of
this study was to provide a detailed discussion of the available
work on this topic, as well as known modes of action of caf-
feine that are relevant to these two conditions. After an exten-
sive review of the literature, we found that both diseases have
decreased intracellular cAMP levels in cutaneous leucocytes, so
it is very likely that being a methylxanthine, and hence a
phosphodiesterase inhibitor, caffeine raises intracellular cAMP
levels, which suppresses inflammatory pathways and potenti-
ates anti-inflammatory ones. Moreover, caffeine is known to
be an ATR (ataxia-telangiectasia mutated) kinase inhibitor and
an ATM (ATM- and Rad3-related) kinase inhibitor, which pro-
motes prompt apoptosis of damaged cells. It was also found
to have antinecrotic effects in cells damaged by reactive oxy-
gen species (ROS). These proapoptotic and antinecrotic prop-
erties may also be reducing the inflammation. Finally,
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
20 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
79ABSTRACTS
caffeine’s metabolites have shown antioxidizing effects against
ROS, which certainly would reduce inflammation caused by
lipid peroxidation, DNA damage and organelle destruction.
We find that caffeine acts in a number of ways to improve
symptoms of inflammation and that it is an effective adjunct
to therapy in AD and psoriasis.
P011Population pharmacokinetic modelling oftildrakizumab (MK-3222), an anti-interleukin-23-p19 monoclonal antibody, in healthy volunteersand patients with psoriasisP. Jauslin,1 P. Kulkarni,1 R. Wada,1 S. VataKuti,1
A. Hussain,2 L. Wenning2 and T. Kerbusch11Certara U.S.A., Inc., Princeton, NJ, U.S.A. and 2Merck & Co., Inc.,
Kenilworth, NJ, U.S.A.Tildrakizumab is an anti-interleukin (IL)-23p19 monoclonal
antibody in development for the treatment of chronic plaque
psoriasis. In this analysis, we characterize the population phar-
macokinetics (PK) of tildrakizumab and identify covariates
influencing its exposure. A population PK model was devel-
oped using six studies conducted in 2098 healthy volunteers
and patients with psoriasis. The model was found to be robust
and predictive using a nonparametric bootstrap and predic-
tion-corrected visual predictive check, respectively. Covariates
of interest included body weight, formulation type, sex, age,
race, serum albumin and ethnicity. The PK were described by
a one-compartment model with first-order absorption and
elimination kinetics, and interindividual variability on clear-
ance, volume of distribution and absorption rate constant. The
PK of tildrakizumab were characterized by low clearance and
limited volume of distribution. In patients with psoriasis, the
geometric mean clearance was 0.32 L per day (38%), the vol-
ume of distribution was 10.8 L (24%), and the absorption
and elimination half-lives were 1.5 days (18%) and 23.4 days
(23%), respectively, with an absorption lag time of 0.05 days
(1.2 h). For the 100-mg dose, the steady state area under the
curve0–tau and Cmax were 305 lg day mL�1 (41%) and 8.1 lgmL�1 (34%), respectively. The corresponding values for the
200-mg dose were 612 lg day mL�1 (40%) and 16.3 lgmL�1 (33%), respectively. For both doses, Tmax was 6.2 days
(46%). Steady state is achieved by 16 weeks with the clinical
regimen (dosing on weeks 0 and 4 and every 12 weeks there-
after), with 1.1-fold accumulation in Cmax. Healthy patients
had 31% higher bioavailability than those with psoriasis.
Patients with increased bodyweight had lower areas under the
curve than those with lower bodyweight. Clinical comparabil-
ity was defined by the observation that no marked differences
in efficacy (Psoriasis Area and Severity Index response) and
safety (adverse events) were seen in exposure split by quartile
for 100 mg and 200 mg. Thus, bounds were defined by the
median exposure of the extreme quartiles. All covariate effects
(intrinsic and extrinsic factors) resulted in exposures contained
within the clinical comparability bounds for all covariates
including bodyweight. These population PK findings indicate
that the PK for tildrakizumab behave like those of a typical
monoclonal antibody. Based on PK data only, there is no need
for dosage adjustment for these intrinsic and extrinsic factors.
Nonetheless, bodyweight was influential and was subsequently
evaluated in a PK–pharmacodynamics model.
P012
Poster withdrawn.
P013Immune modulation by topical PH-10 aqueoushydrogel (rose Bengal disodium) in psoriasislesionsJ.G. Krueger,1 S. Garcet,1 J. Fuentes-Duculan,2
N. Kunjravia,1 I. Cueto,1 X. Li,1 J.M. Singer3 andE.A. Wachter31Rockefeller University, New York, NY, U.S.A., 2Rockefeller University, New
York, Sint Maarten (Dutch part), NY, U.S.A. and 3Provectus
Biopharmaceuticals, Knoxville, TN, U.S.A.PH-10 is topical hydrogel formulation that yields selective
delivery of rose Bengal disodium (RB) to epithelial tissues. RB
is a fluorescein derivative capable of producing singlet oxygen
upon photoactivation, but its therapeutic mechanism in psori-
asis vulgaris is not established. We thus conducted a mecha-
nistically focused study of PH-10 in 30 patients with psoriasis
vulgaris using sequential vehicle and active drug treatment for
4 weeks each (registered clinical trial NCT02322086). Skin
biopsies were collected before treatment and at the end of
each treatment period. Effects of placebo vs. active treatment
were assessed on cellular immune infiltrates, driver cytokines
of psoriasis and the overall disease transcriptome using
immunohistochemistry and gene-expression profiling with
Affymetrix U133 2.0Plus arrays and reverse-transcriptase poly-
merase chain reaction (RT-PCR). Vehicle treatment for
4 weeks did not significantly alter expression of core inter-
leukin (IL)-23/IL-17-modulated genes or the overall disease
transcriptome (using a principle component analysis, PCA).
However, 4 weeks of treatment with PH-10 significantly (fold
change > 1.5, P < 0.05) downregulated IL-17A, IL-22, IL-26,
IL-36, and keratin 16 mRNAs as assessed by RT-PCR, while a
PCA analysis of the gene array results showed a shift towards
nonlesional skin with some post-treatment biopsies clustering
within the nonlesional skin profile. Pathways that were signifi-
cantly improved by PH-10 included published psoriasis tran-
scriptomes and cellular responses mediated by IL-17, IL-22
and interferons. To strengthen the analysis of immune- and
psoriasis-related gene modulation by PH-10, we divided
patients into responders vs. nonresponders based on the PCA
analysis after 4 weeks of treatment (comparing to nonlesional
skin at baseline). Using this approach, more than 500 disease-
related genes were downregulated during 4 weeks of treat-
ment with PH-10, and expressions of a wide range of central
‘psoriasis related’ genes including IL-23, IL-17, IL-22,
S100A7, IL-19, IL-36 and CXCL1 were effectively normalized;
treated lesional skin had values in the same range as baseline
nonlesional skin. We also measured decreased expression of
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 21
T-cell activation markers including ICOS and CTLA4, changes
that were paralleled by decreases in myeloid (CD11c+) den-
dritic cells and T cells using immunohistochemical measures.
The results of this study establish that PH-10 has highly sig-
nificant ability to modulate psoriatic inflammation, including
key cytokine drivers of this disease, but only a subset of
patients revert from the lesional phenotype to that of nonle-
sional skin. This type of ‘mixed’ response outcome occurs
with other topical or systemic drugs now approved for psoria-
sis, highlighting a need to personalize treatments and poten-
tially to have predictive response biomarkers for individual
drugs.
P014Favourable safety profile of ixekizumab: resultsfrom 11 moderate-to-severe psoriasis and threepsoriatic arthritis clinical trialsA. Gottlieb,1 K. Papp,2 W. Xu,3 L. Mallbris3 andN. Agada31Department of Dermatology, New York Medical College, Metropolitan
Hospital New York, NY, U.S.A.; 2Probity Medical Research, Waterloo, ON,
Canada and 3Eli Lilly and Company, Indianapolis, IN, U.S.A.Ixekizumab (IXE) is a high affinity anti-interleukin (IL)-17A
monoclonal antibody. The objective of this report is to pro-
vide an overview of safety from IXE clinical trials in psoriasis
and psoriatic arthritis (PsA). Study results for psoriasis and PsA
have been published separately. IXE psoriasis safety data were
integrated from 11 controlled and uncontrolled clinical trials
in patients with moderate-to severe plaque psoriasis, including
the phase III trials UNCOVER-1, -2 and -3. Integrated IXE PsA
safety data were from three controlled and uncontrolled clini-
cal trials in patients with active PsA, including the phase III
trials SPIRIT-P1 and -P2. Frequencies of treatment-emergent
adverse events (TEAEs) and adverse events of special interest
(AESI) are provided here. Exposure-adjusted incidence rates
(IRs) of AESIs were summarized. The IR is expressed as the
number of unique patients with a particular AESI per 100
patient-years (PY), using the entire duration of exposure dur-
ing treatment period. The 95% confidence interval of the IR
was calculated based on the Poisson regression model with
treatment as the explanatory variable. Major adverse cerebro-
cardiovascular events were adjudicated by an external adjudi-
cation committee. A total of 5689 patients (12061.5 PY) with
psoriasis and 1118 patients (1373.4 PY) with PsA were
exposed to IXE. TEAEs, mostly mild or moderate, were
reported by 4775 (83.9%) patients with psoriasis and by 868
(77.6%) patients with PsA. Injection-site reactions, mostly
mild or moderate, were reported by 840 (14.8%) patients
with psoriasis and by 227 (20.3%) patients with PsA, and
rarely resulted in study drug discontinuation. The IRs of injec-
tion-site reactions decreased substantially over time in both
patients with psoriasis and those with PsA. Serious adverse
events occurred among 670 (11.8%) and 91 (8.1%) patients
with psoriasis and PsA, respectively. Adverse events leading to
discontinuation of study drug occurred among 379 (6.7%)
patients with psoriasis and 80 (7.2%) patients with PsA. There
were 23 (0.4%) deaths among patients with psoriasis and two
(0.2%) deaths among patients with PsA. Most deaths resulted
from cardiovascular events in those with a history of risk fac-
tors, and none was attributed to the study drug. The present
report supports a favourable safety profile of ixekizumab in
different patient populations, those with moderate-to-severe
psoriasis and those with active PsA. This study was funded by
Eli Lilly and Company, Indianapolis, IN, U.S.A.
P015
Poster withdrawn.
P016Cytokine effects of apremilast as a mechanism ofefficacy in systemic-naive patients with moderateplaque psoriasis: results from the UNVEIL trialB. Strober,1,2 M. Alikhan,3 B. Lockshin4 andP. Schafer51University of Connecticut, Farmington, CT, U.S.A.; 2Probity Medical
Research, Waterloo, ON, Canada; 3University of Cincinnati Medical Center,
Health Dermatology, Cincinnati, OH, U.S.A.; 4DermAssociates, Silver Spring,
MD, U.S.A. and 5Celgene Corporation, Summit, NJ, U.S.A.Previous pharmacodynamic (PD) subanalyses of clinical trials
have demonstrated that the effects of apremilast on key cyto-
kines involved in the pathogenesis of plaque psoriasis play a
role in determining clinical efficacy. It was therefore of inter-
est to perform a more detailed PD substudy of a phase IV ran-
domized, controlled trial (UNVEIL), which evaluated the
efficacy and safety of apremilast 30 mg twice daily (APR) in
the treatment of systemic-naive patients with moderate plaque
psoriasis [psoriasis-involved body surface area (BSA) 5%,10%;
static Physician’s Global Assessment = 3 (moderate)]. Patients
were randomized (2 : 1) to APR or placebo (PBO) for
16 weeks. From the PD patient subset, blood samples obtained
at weeks 0 (baseline), 4 and 16 were analysed for interleukin
(IL)-17A, IL-17F, IL-22, IL-23; leptin; adiponectin;
apolipoproteins A-I, A-II, B and E; and numbers of circulating
T helper 17 (Th17) cells, regulatory T cells (Tregs) and total
T-cell numbers. Correlations were examined between percent-
age change from baseline in key inflammatory biomarkers and
clinical efficacy, based on assessments using the product of the
sPGA and psoriasis-involved BSA (PGA 9 BSA). Of the total
221 patients randomized into the phase IV trial, the PD sub-
population included 38 patients (APR, n = 26; PBO, n = 12).
At week 4, the median percentage changes from baseline in
IL-17A, IL-17F, IL-22 and IL-23 with APR vs. PBO were
�42.5% vs. 9.3% (P= 0.019), �64.4% vs. 12.8% (P<
0.001), �42.9% vs. 8.6% (P= 0.0021) and �15.2% vs.
�6.6% (P = 0.69). At week 16, percentage change in IL-17A
significantly correlated with percentage change (improvement)
in PGA 9 BSA (r = 0.45, P= 0.04). At weeks 4 and 16, levels
of leptin, adiponectin and apolipoproteins A-I, A-II, B and E,
as well as numbers of circulating Th17 cells, Tregs, and total
T cells, were largely unchanged from baseline. Improvements
in clinical signs and symptoms of psoriasis at week 16, based
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
22 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
81ABSTRACTS
on PGA 9 BSA, correlated with apremilast-mediated decreases
in IL-17A without affecting upstream systemic IL-23 levels
and without affecting the number of Th17 cells or Tregs.
Apremilast had no effect on adipokines or apolipoproteins.
This study was funded by Celgene Corporation.
P017Patient- and physician-reported outcomes withapremilast for patients with plaque psoriasisduring routine dermatology care in Germany:an interim analysisK. Reich,1 S. Bomas,2 B. Korge,3 M. Manasterski,4
U. Schwichtenberg,5 H. Mentz,6 K. Groegel6 andN. N�unez G�omez6
1SCIderm Research Institute and Dermatologikum Hamburg, Hamburg,
Germany; 2Praxis Dr. med. S. Rotterdam, Gelsenkirchen-Feldmark, Germany;3Priv. Doz. Dr. med. Korge, D€uren, Germany; 4Hautarztpraxis Manasterski
und Dues, Berlin, Germany; 5Derma Nord Hautarztpraxen Dr. med.
Schwichtenberg, Bremen, Germany and 6Celgene GmbH, Munich, GermanyLAPIS-PSO (ClinicalTrials.gov NCT02626793) is an ongoing,
52-week, prospective, multicentre, noninterventional, observa-
tional cohort study in real-world dermatology clinical settings
in Germany. LAPIS-PSO is evaluating patient- and physician-
reported outcomes of quality of life, treatment satisfaction and
treatment effectiveness in patients with psoriasis during long-
term apremilast therapy. The primary end point is the propor-
tion of patients who achieve a Dermatology Life Quality Index
(DLQI) score ≤ 5 or an improvement in the DLQI score by ≥ 5
points from baseline. Presented here is a 4-month interim
analysis of patient-reported outcomes and efficacy assessments
of apremilast among enrolled patients (n = 111; full analysis
set, n = 73) who were continuing apremilast therapy at
4 months. At baseline, the mean age was 50.9 � 13.2 years
in the full analysis set, and 38 patients (52%) are female. At
the time of apremilast initiation, 63 patients (86%) had Physi-
cian’s Global Assessment (PGA) of disease severity ≥ 3; the
mean psoriasis-involved body surface area (BSA) was 22.9%,
the mean pruritus visual analogue scale (VAS) score was
57.8 mm, and the mean DLQI score was 14.6. Among
patients who were continuing apremilast therapy at 4 months,
a total of 41 of 64 patients (64%) achieved the primary end
point of either DLQI ≤ 5 or DLQI reduction ≥ 5. Mean per-
centage improvements were observed for BSA
(�10.3 � 14.7) and pruritus VAS (�48.0%); 27% of patients
achieved a PGA rating of 0 (clear) or 1 (minimal), and 31%
had a PGA rating of 0 or 1. Post hoc Spearman correlation
analyses showed that reductions from baseline in pruritus VAS
score were highly correlated with reduction in scalp psoriasis
severity (r = 0.59) and improvement in DLQI score
(r = 0.68). Responses on the Systemic Therapy Adherence
Questionnaire (STAQ) showed that most patients (> 50%)
who were continuing apremilast therapy at month 4 agreed or
strongly agreed that they were satisfied with apremilast tolera-
bility, would continue with apremilast therapy, and would
recommend it to other patients. Substantial proportions indi-
cated satisfaction with apremilast efficacy (49%) and onset of
effect (47%); 42% indicated that their therapeutic goals had
been met. A total of 27 patients (25%) reported at least one
adverse event (AE). There was one AE that occurred in ≥ 5%
of patients (diarrhoea, n = 9, 8%). AEs were consistent with
the known safety profile of apremilast. In clinical routine care
in Germany, outcomes of apremilast treatment for patients
with psoriasis were comparable with results from apremilast
clinical trials. This study was funded by Celgene Corporation.
P018Shear wave elastography in patients on high-dosemethotrexate: a prospective studyD. Kivelevitch,1 R. Rahimi2 and A. Menter11Division of Dermatology and 2Transplant Hepatology, Baylor Scott & White,
Dallas, TX, U.S.A.Long-term methotrexate (MTX) use in the psoriasis population
may be associated with liver fibrosis. Multidisciplinary special-
ists and society guidelines differ in their approaches for estab-
lishing liver fibrosis. We examined the role of noninvasive
assessment of fibrosis using ultrasound-based shear wave elas-
tography (SWE) in patients predominantly with psoriasis and
rheumatoid arthritis on long-term MTX treatment. In this
prospective study, 91 patients on high-dose MTX were evalu-
ated using SWE. Fibrosis stage was defined as: 6–7.9 kPa
(stage 1); 8–9.9 kPa (stage 2); 10–11.9 kPa (stage 3) or ≥12 kPa (stage 4 or early cirrhosis). In a subset, liver stiffness
(in kPa) was correlated with fibrosis stage on liver biopsy
based on the results of SWE and risk factors for metabolic syn-
drome. Between January 2014 and May 2016, 91 patients
were enrolled: mean age 61 years, 76% female; 59% with
psoriasis (52 patients), 30% rheumatoid arthritis (26 patients)
and 11% other (seven patients); mean body mass index (BMI)
32.1 � 7.9 kg m�2; on a mean high cumulative MTX dose of
5374 � 3391 mg. Nonalcoholic fatty liver disease (based on
imaging or history) and diabetes were seen in 38 (42%) and
19 (21%) patients, respectively. Six patients were excluded
due to missing data. Eighty-one per cent underwent SWE and
38% underwent concomitant liver biopsy. Overall 82% had an
abnormal result suggesting presence of fibrosis (METAVIR
score ≥ F1); the incomplete or unreliable rate was 7% (n = 6)
seen in patients with morbid obesity (BMI 37 kg m�2). The
mean stiffness was 9.7 � 4.8 kPa, suggestive of stage 2 fibro-
sis. Twelve per cent had stiffness > 12 kPa; however, liver
biopsy did not show any cirrhosis, but rather stage 0 (n = 3),
stage 1 (n = 6) and stage 3 (n = 2) were represented. None
of the patients with normal stiffness or a value ≤ 12 kPa had
cirrhosis on biopsy. Being obese increased the likelihood of
obtaining any abnormal SWE result compared with overweight
patients (P = 0.049). Mean platelets, total bilirubin, alkaline
phosphatase, aspartate aminotransferase, alanine aminotrans-
ferase and international normalized ratio did not differ
between those receiving liver biopsy and those assessed with
SWE alone. In patients on high cumulative doses of MTX,
SWE overestimated the presence of advanced fibrosis, specifi-
cally in obese patients. Furthermore, the negative predictive
value for absence of advanced fibrosis was high, suggesting
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 23
that SWE is helpful for screening out patients who do not
have advanced fibrosis. The role of serial SWE in patients with
psoriasis using MTX is currently being evaluated.
P019Do patients with certain human leucocyte antigenexpression have a higher risk of developingpsoriasis?A. Anandan, K. Radhakrishnan, R. Prasada andV.K. PanickerSri Ramachandra University, Chennai, IndiaPsoriasis is an immune-mediated genetically determined skin
disorder affecting 1–3% of people worldwide. Psoriasis is a
multifactorial disease and has been associated with certain
human leucocyte antigen (HLA) expressions. This study is
focused on HLA association in psoriasis by screening patients
with psoriasis for HLA class I and determining its odds ratio
(OR). The study was conducted at the department of trans-
fusion medicine at a tertiary-care hospital. In total 100
patients with psoriasis (cases) and 100 controls (healthy blood
donors) were enrolled in the study. Samples from the patients
with psoriasis were collected from dermatology outpatient
department and the samples from the controls were taken
from voluntary blood donors at the department of transfusion
medicine after obtaining consent. HLA typing for class I was
done using the single specific primer polymerase chain reac-
tion method. The HLA results were statistically analysed and
the association with psoriasis was determined. The alleles that
were found in higher frequency among the cases were HLA-
A*02 (45%, OR 2.33) and HLA-A*24 (35%, OR 2.15). HLA-
B*35 (36%, OR 2.40) was observed at a higher frequency
among the cases. HLA-C*06 and HLA-C*07 were found in 52%
and 33% of samples and had ORs of 9.75 and 2.06, respec-
tively among the patients. Certain HLA alleles are present in
higher frequency in the disease population than in the con-
trols, implying that individuals expressing these alleles may
have a higher relative risk of developing psoriasis.
P020Utility study to map utilities to the Psoriasis Areaand Severity Index and Dermatology Life QualityIndex instruments in patients with chronic plaquepsoriasisC. Baker,1,2 J. Sullivan,3 P. Davey4 and J. Wilson5
1Skin and Cancer Foundation Inc., Melbourne, Australia; 2St Vincent’s
Hospital, Melbourne, Australia; 3Holdsworth House Dermatology, Sydney,
Australia; 4Illuminate Health Consulting, Sydney, Australia and 5AbbVie,
Sydney, AustraliaNational funding bodies such as the U.K. NICE, Scotland’s
SMC and Australia’s PBAC have a preference for cost utility
analyses to determine cost-effectiveness when making deci-
sions regarding funding of new treatments. No published
studies currently exist that allow the Psoriasis Area and Sever-
ity Index (PASI) or Dermatology Life Quality Index (DLQI)
instruments to be validly converted to utilities. The purpose of
the study was to generate utility weights that correspond to
the full range of scores from the PASI and DLQI. Study partici-
pants (total 74) were from two psoriasis treatment clinics in
Australia. Patient information for the utility instruments was
collected in face-to-face interviews. Informed consent was
obtained and the study approved by a local ethics committee.
To assess the relationship between the PASI and DLQI instru-
ments and utilities, curve-fitting procedures were performed.
The proportion of variance or multiple correlation coefficients
(R2) that could be explained by the model were indicated by
a goodness of fit. The curves explored include linear, squared,
cubic, polynomial, logarithmic and square root. Subgroups
were selected for stratification to ensure that there were suffi-
cient data points across the range of PASI scores (0–72). Thedata were sampled into subgroups according to the following
PASI scores: 0–3, 3–10, 10–15 and 15–72. Three instruments
were administered during the full study: two disease-specific
instruments measuring psoriasis severity, the PASI and the
DLQI, and a general quality-of-life (QoL) instrument measur-
ing patient utility, the EuroQol-5D (EQ-5D). The DLQI is a
disease-specific QoL instrument with higher scores indicating
a more impaired quality of life. In contrast the EQ-5D mea-
sures health states on a 0–1 scale where higher scores reflect
an improved health state. A number of patient responses were
excluded based on illogical or incomplete responses, leaving
56 patient responses for analysis. The correlations between
EQ-5D and PASI and EQ-5D and DLQI were highly significant
(P < 0.001), with negative coefficients. Furthermore, the asso-
ciation between EQ-5D and DLQI appears to be stronger than
that between EQ-5D and PASI. In conclusion, EQ-5D utility
decreases when the PASI or DLQI score increases, meaning
that as symptoms increase patients report poorer quality of
life. The results from this study were consistent with two pre-
vious studies that attempted to map utilities to psoriasis symp-
toms, with a square-root predictive model showing no
substantial difference.
P021Secukinumab shows high and sustained efficacy innail psoriasis: 2.5-year results from theTRANSFIGURE studyK. Reich,1 P. Arenberger,2 U. Mrowietz,3 S. Jazayeri,4
M. Augustin,5 A. Parneix,6 P. Regnault,7 R. You8 andJ. Frueh71Dermatologikum Hamburg and SCIderm Research Institute, Hamburg,
Germany; 2Department of Dermatology, Charles University, Prague, Czech
Republic; 3Psoriasis Center at the Department of Dermatology, University
Medical Center Schleswig-Holstein, Kiel, Germany; 4Alliance Dermatology and
MOHS Center, Phoenix, AZ, U.S.A.; 5Universit€at Hamburg, Hamburg,
Germany; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, U.S.A.;7Novartis Pharma AG, Basel, Switzerland and 8China Novartis Institutes for
BioMedical Research, Shanghai, ChinaNail psoriasis is associated with decreased finger mobility,
functional impairment, pain and reduced quality of life and is
often difficult to treat. It correlates with more severe psoriatic
disease and is an important predictor of psoriatic arthritis
(PsA). Nails are affected in up to 50% of patients with
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
24 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
83ABSTRACTS
psoriasis, with a lifetime incidence as high as 90%. Secuk-
inumab, a fully human monoclonal antibody that selectively
neutralizes interleukin-17A, has demonstrated significant effi-
cacy in the treatment of moderate-to-severe psoriasis and PsA,
demonstrating a rapid onset of action and sustained responses
with a favourable safety profile. Here we report the long-term
follow-up efficacy and safety results from the TRANSFIGURE
study, the first robust (2.5-year) data reported in patients with
nail psoriasis treated with secukinumab. TRANSFIGURE is a
double-blind, randomized, placebo-controlled, parallel-group,
multicentre phase IIIb study to investigate the safety and effi-
cacy of secukinumab 150 and 300 mg subcutaneous in mod-
erate-to-severe nail psoriasis, involving 198 patients. As
previously reported, at week 16 the primary end point NAPSI
(Nail Psoriasis Severity Index) and all secondary end points of
this study were met, demonstrating superiority of secuk-
inumab over placebo after 16 weeks of placebo-controlled
treatment.2 An interim analysis at week 80 demonstrated the
continuation of improvement in nail psoriasis for all efficacy
parameters. The effect was sustained through 2.5 years with
large mean NAPSI improvements from baseline of �73.3%
and �63.6% with secukinumab 300 mg and 150 mg, respec-
tively (as observed). Secukinumab demonstrated sustained
reductions (improvements) in total mean NAPPA (Nail Assess-
ment in Psoriasis and Psoriatic Arthritis) quality-of-life scores
from baseline to 2.5 years by �52.4% (300 mg) and �18.1%
(150 mg), and 70.2% (300 mg) and 71.0% (150 mg) of
patients achieved a weighted NAPPA-Patient Benefit Index glo-
bal score of ≥ 2 (at least moderate benefits) (last observation
carried forward). Patients showed considerable improvements
in EQ-5D (EuroQoL 5-Dimension Health Status Questionnaire)
compared with baseline, reporting decreased pain and discom-
fort. The safety profile was consistent with that observed in
previous phase III trials of psoriasis and PsA. TRANSFIGURE is
the first large, randomized controlled trial to report long-term
results in patients with nail psoriasis. Secukinumab demon-
strated strong sustainability of clinically meaningful efficacy,
large quality-of-life improvement and a favourable safety pro-
file up to 2.5 years in difficult-to-treat nail psoriasis. This
investigation was sponsored by Novartis Pharma AG, Basel,
Switzerland.
P022Secukinumab pooled and long-term safety:analysis of 19 psoriasis clinical trialsP. van de Kerkhof,1 K. Reich,2 C. Leonardi,3
A. Blauvelt,4 N. Mehta,5 T.-F. Tsai,6 R. You,7
P. Papanastasiou,8 M. Milutinovic8 andC.E.M. Griffiths91Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands;2Dermatologikum Hamburg and Georg-August-University, G€ottingen,
Germany; 3Saint Louis University Health Sciences Center, St Louis, MO,
U.S.A.; 4Oregon Medical Research Center, Portland, OR, U.S.A.; 5National
Heart, Lung, and Blood Institute, Bethesda, MD, U.S.A.; 6National Taiwan
University College of Medicine, Taipei, Taiwan; 7China Novartis Institutes
for BioMedical Research, Shanghai, China; 8Novartis Pharma AG, Basel,
Switzerland and 9University of Manchester, Manchester, U.K.We report exposure adjusted incidence rates (IRs) for treat-
ment-emergent adverse events per year from a pooled analysis
of all secukinumab psoriasis trials to date (19 studies, 4674
Year 1 Year 2 Year 3 Year 4 Year 5Secukinumab ETN UST PBO Secukinumab Secukinumab Secukinumab Secukinumab
Dose (mg) Any 300 50 45/90 Any 300 Any 300 Any 300 Any 300Patients 4676 1773 323 336 1090 3423 1188 1972 572 1522 397 909 263
Exposure(patient-years)
4093.5 1467.4 296.9 318.1 301.2 2631.3 859.6 1659.6 423.0 1392.2 377.5 291.6 90.0
Any AEs 254.1 275.6 245.7 252.2 355.8 169.9 168.1 159.8 160.2 104.1 111.9 12.0 13.9Frequent AEs
Nasopharyngitis 27.4 28.4 35.9 31.2 35.9 22.7 21.2 23.2 24.1 14.4 11.8 1.0 3.4Headache 10.5 12.6 15 14.6 23.7 5.1 5.4 4.8 4.3 3.4 4.9 0.0 0.0
URTI 8.8 9.1 5.9 9.9 8.8 7.2 7.3 6.9 6.1 5.2 5.5 0.0 0.0Selected AEs
Opportunisticinfections
0.2 0.2 0.3 0.3 0.3 0.1 0.1 0.0 0.0 0.1 0.0 0.0 0.0
Candida infections 3.1 4.7 1.4 1.6 1.7 2.0 3.6 1.4 1.9 1.5 1.3 0.3 1.1Neutropenia 0.5 0.5 1.4 0.0 0.0 0.3 0.1 0.2 0.0 0.1 0.0 0.0 0.0
MACE 0.4 0.5 0.3 0.3 1.3 0.1 0.1 0.3 0.5 0.4 0.0 0.0 0.0Crohn disease 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
Ulcerative colitis 0.2 0.1 0.3 0.0 0.0 0.2 0.4 0.1 0.2 0.1 0.3 0.0 0.0Malignant or
unspecified
tumours(except
NMSC)
0.5 0.4 0.3 0.3 0.3 0.3 0.4 0.5 0.2 0.2 0.0 0.0 0.0
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 25
patients, 10 061 patient-years of exposure). Adverse event
(AE) IRs (per 100 patient-years) were examined per year for
patients who received either secukinumab 300 mg or any
dose of secukinumab, and, for 1 year only, for patients receiv-
ing placebo (PBO), etanercept (ETN) 50 mg or ustekinumab
(UST) 45/90 mg. The pooled safety of secukinumab remained
favourable over 5 years of treatment with no increase of AEs
over time. Additionally, secukinumab demonstrated a compa-
rable pooled safety profile to that of PBO, ETN and UST over
the course of 1 year (see Table; MACE, major adverse cardio-
vascular event; NMSC, nonmelanoma skin cancer; URTI, upper
respiratory tract infection). This comprehensive pooled analy-
sis supports the favourable long-term safety profile of secuk-
inumab in patients with psoriasis. This investigation was
sponsored by Novartis Pharma AG, Basel, Switzerland.
P023Lysosomal action in the regulation of inflammatoryprocesses on the example of psoriasisK. Boche�nska,1 M. Moskot,2 E. Smoli�nska,1
J.J.-Banecka1 and M. Gabig-Cimi�nska21Department of Medical Biology and Genetics, University of Gda�nsk, Gda�nsk,
Poland and 2Institute of Biochemistry and Biophysics, Polish Academy of
Sciences, Laboratory of Molecular Biology (affiliated with the University of
Gda�nsk), Gda�nsk, PolandChronic inflammation is strongly associated with the patho-
genesis of many dermatological diseases, including psoriasis.
Despite the ever-growing knowledge of the causes and devel-
opment of abnormal immune responses, factors involved in
these processes are still being sought. The main goal of the
following research is clarification the role of lysosomes in the
development of inflammation and results obtained regarding
correlation with calcium ion levels and calcineurin activity at
later stages. Studies are carried out on three models: (i) in vitro
‘psoriasis-like’ activated HaCaT cells, (ii) in vitro keratinocytes
derived from patient tissue (from lesional and nonlesional
psoriatic skin and normal skin as a control), and (iii) ex vivo
directly on skin tissue biopsies (from lesional and nonlesional
psoriatic skin and normal skin as a control). Preliminary analy-
ses were designed to examine changes in the amount of lyso-
somes in the HaCaT cell line. Keratinocytes were treated with
proinflammatory cytokines [interleukin (IL)-1A, IL-17A,
IL-22, oncostatin M and tumour necrosis factor-a] to achieve
the ‘psoriasis-like’ phenotype, and then stained for the fluores-
cence microscope images. In the course of this work we con-
cluded that the number of lysosomes is reduced in stimulated
keratinocytes compared with controls (nonactivated cells). To
verify the validity of the obtained data, the expression of
genes responsible for lysosomal biogenesis (i.e. MiT family
genes: TFE3, TFEB, TFEC and MITF) by real-time quantitative
reverse-transcriptase polymerase chain reaction in patients’
skin biopsies was examined. The results showed downregula-
tion of TFE3, TFEB and MITF in both lesional and nonlesional
psoriatic skin compared with the normal skin from healthy
individuals. In turn, the level of the TFEC gene was elevated in
both cases, or unchanged in lesional vs. nonlesional tissue.
The above data indicate potential lysosome biogenesis distur-
bances, in the direction of lowering the efficiency of this pro-
cess in skin of patients with psoriasis. The obtained results
were compared with the activity of genes encoding calcineurin
subunits PPP3CA and PPP3CB. We observed reduced expres-
sion of both genes in psoriatic skin tissue, which may indicate
that dysfunction of factors in the MiT family can be aggra-
vated by impaired calcium homeostasis and their regulation
by calcineurin. These data may complement the lack of
knowledge about the role of lysosomes in the development of
inflammation of the skin and contribute to the development
of new therapeutic targets and strategies.
P024Secukinumab demonstrates significantly lowerimmunogenicity potential than ixekizumab inhuman in vitro assaysS. Spindeldreher,1 B. Maill�ere,2 E. Correia,2
M. Tenon,2 A. Karle,1 P. Jarvis1 and F. Kolbinger11Novartis Pharma AG, Basel, Switzerland and 2CEA-Saclay, Institute Frederic
Joliot, Gif sur Yvette, FranceSecukinumab, a fully human monoclonal antibody (mAb) that
selectively neutralizes interleukin-17A, has significant efficacy
in the treatment of moderate-to-severe plaque psoriasis and
psoriatic arthritis (PsA). It demonstrates a rapid onset of action
and sustained responses with a favourable safety profile and
< 1% immunogenicity in the phase III programme. Secuk-
inumab has previously demonstrated lower potential for
immunogenicity than other biotherapeutics used to treat psori-
asis and PsA in in vitro assays. Here we extended the analysis
and compared the T-cell precursor frequencies against 4 mAbs
(secukinumab, ixekizumab, adalimumab and ustekinumab).
Two sets of 16 healthy donors were analysed (study 1 and
study 2). Immunogenic potential was evaluated using an
in vitro T-cell-amplification assay to measure the frequency of
mAb-specific pre-existing T cells from these donors. Mono-
cyte-derived dendritic cells (DCs) were generated from
peripheral blood mononuclear cells and exposed in vitro to
mAbs or a positive control (keyhole limpet haemocyanin) and
matured. CD4 T cells were stimulated by matured protein-
loaded DCs and cultured for 21 days. An Elispot assay was
used to assess the antigen specificity of T-cell lines. The fre-
quency of pre-existing specific T cells was calculated from the
proportion of culture wells that reacted to the protein. The
data were analysed using a Wilcoxon rank test. In study 1,
one of 16 donors responded to secukinumab, generating one
T-cell line (mean frequency 0.02 cells per million T cells; low
immunogenicity potential). In contrast, nine of 16 donors
responded to ixekizumab (35 T-cell lines, frequency 0.54),
nine of 16 responded to adalimumab (15 T-cell lines, 0.21)
and six of 15 responded to UST (14 T-cell lines, 0.19), show-
ing moderate immunogenic potential. In study 2, one of 15
generated T-cell lines was specific for secukinumab, with a
mean frequency of 0.03 cells per million CD4 T cells (low
immunogenicity potential), while seven donors responded to
ixekizumab, with a frequency of 0.21–0.67 specific CD4 T
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
26 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
85ABSTRACTS
cells per million CD4 T cells (mean 0.16) (moderate immuno-
genicity potential). Secukinumab showed a low number of
donors responding with a low T-cell precursor frequency
compared with other mAbs and therefore has significantly
lower immunogenic potential. This is in line with observed
clinical immunogenicity rates. This investigation was spon-
sored by Novartis Pharma AG, Basel, Switzerland.
P025Decreased expression of interleukin-27 inmoderate-to-severe psoriasis and its anti-inflammatory role in an imiquimod-inducedpsoriasis-like mouse modelW. Chen,1 Y. Gong,1 X. Zhang,2 Y. Tong,1 X. Wang,3
C. Fei,1 H. Xu,1 Q. Yu,1 Y. Wang1 and Y. Shi11Shanghai Tenth People’s Hospital, Tongji University School of Medicine,
Shanghai, China; 2Second Military Medical University, Shanghai, China and3Huashan Hospital, Fudan University, Shanghai, ChinaPsoriasis is a T-cell-mediated chronic inflammatory skin dis-
ease characterized by aberrant keratinocyte hyperproliferation.
A recent study reported that interleukin (IL)-27, which plays
a versatile role in inflammatory skin disorders, could induce
the function of T helper (Th)1 cells in psoriasis. Further
studies found a suppression role of IL-27 to Th17. Here we
investigated and compared the expression of IL-27 and its
receptor in patients with moderate-to-severe psoriasis vs.
healthy controls. We further identified the role of IL-27 in
an imiquimod-induced psoriasis mouse model by injection
with IL-27 or IL-27p28 antagonist. The results showed that
the protein expression and distribution of IL-27 and its
receptor were decreased in the skin and peripheral blood of
patients with moderate-to-severe psoriasis compared with
healthy controls, and IL-27 concentration was significantly
decreased in patients with psoriasis. mRNA levels of
IL-27p28, WSX-1 and gp130 in patients with moderate-to-
severe psoriasis were significantly lower than those of
healthy controls; however, the expression level of EBI3
mRNA did not vary remarkably. Imiquimod-induced mice
treated with IL-27 showed a relatively mild clinical manifes-
tation. However, blocking the role of IL-27p28 in imiqui-
mod-induced mice significantly aggravated disease, and a
significant elevation of proinflammatory cytokines (inter-
feron-c and IL-17) was also observed. All these data sug-
gested that IL-27 may possibly act as an anti-inflammatory
cytokine in psoriasis. Our study also indicated the potential
function of IL-27 in psoriasis immunotherapy.
P026Secukinumab shows high and sustained efficacy inpatients with moderate-to-severe palmoplantarpsoriasis: 2.5-year results from the GESTURE studyA. Gottlieb,1 J. Sullivan,2 A. Kubanov,3 R. You,4
P. Regnault5 and J. Frueh51New York Medical College, New York, NY, U.S.A.; 2Holdsworth House
Medical Practice, Darlinghurst, Australia; 3State Scientific Center of
Dermatology, Venereology and Cosmetology, Moscow, Russian Federation;
4Novartis Institutes for BioMedical Research, Shanghai, China and 5Novartis
Pharma AG, Basel, SwitzerlandPalmoplantar psoriasis occurs in up to 40% of patients with
plaque psoriasis and is often resistant to treatment. It is associ-
ated with pain, functional limitations and greater impairment
of health-related quality of life compared with plaque psoriasis
on other parts of the body. Secukinumab, a fully human mon-
oclonal antibody that selectively neutralizes interleukin-17A,
has demonstrated significant efficacy in the treatment of mod-
erate-to-severe psoriasis and psoriatic arthritis, indicating rapid
onset of action, sustained responses and a favourable safety
profile. Here we report the long-term follow-up efficacy and
safety results from the GESTURE study, the first robust (2.5-
year) data reported in patients with moderate-to-severe pal-
moplantar psoriasis treated with secukinumab. GESTURE is a
double-blind, randomized, placebo-controlled, parallel-group,
multicentre phase IIIb study to investigate the safety and effi-
cacy of secukinumab 150 and 300 mg subcutaneous in 205
patients with moderate-to-severe palmoplantar psoriasis. As
previously reported, after 16 weeks of placebo-controlled
treatment, the primary end point, palmoplantar Investigator’s
Global Assessment (ppIGA) 0/1, and all secondary end points
of this study were met, demonstrating superiority of secuk-
inumab over placebo at week 16. An interim analysis at week
80 established the continuation of improvement of palmoplan-
tar disease for all efficacy parameters. The effect was sustained
through 2.5 years with 59.2% and 52.5% of patients in the
secukinumab 300-mg and 150-mg groups, respectively (mul-
tiple imputation) achieving clear or almost clear palms and
soles (ppIGA 0/1). Consistently with this observation, the
mean Palmoplantar Psoriasis Area and Severity Index percent-
age change from baseline reached �74.7% and �61.6% for
secukinumab 300 mg and 150 mg, respectively, at 2.5 years
(multiple imputation). The Dermatology Life Quality Index 0
or 1 response was achieved in 45.5% vs. 23.9% of patients in
the secukinumab 300-mg and 150-mg groups, respectively
[last observation carried forward (LOCF)]. Pain and function
of palms and soles were markedly improved with secuk-
inumab, as reflected by the Palmoplantar Quality of Life
Instrument overall scores, with 16.7% and 17.9% patients
experiencing no difficulty in hand and feet functionality in
secukinumab 300-mg and 150-mg groups, respectively
(LOCF). The safety profile was consistent with that seen in
secukinumab phase III trials. The most common adverse events
across all treatment arms were nasopharyngitis, upper respira-
tory tract infection and headache. GESTURE, the largest and
longest-duration randomized controlled trial to date, revealed
that secukinumab provides a novel treatment option for the
difficult-to-treat and infrequently studied palmoplantar psoria-
sis population by providing a strong and sustained response
through 2.5 years. This investigation was sponsored by Novar-
tis Pharma AG, Basel, Switzerland.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 27
P027Efficacy and safety of infliximab in the treatment ofthe Chinese patients with psoriasisJ.-Z. Guo, W.-H. Wang and C.-L. ZhangPeking University Third Hospital, Beijing, ChinaTo analyse the clinical efficacy and safety in Chinese patients
with psoriasis treated with infliximab, all treated inpatients at
the Dermatology Department of Peking University Third
Hospital were reviewed. The types of psoriasis, Psoriasis Area
and Severity Index (PASI) score and clinical response were
analysed. Infliximab was given at a dose of 5 mg kg�1 by
intravenous infusion at weeks 0, 2 and 6, followed by mainte-
nance infusion every 8 weeks. From 2015 to 2017, 27 of 98
inpatients with psoriasis in our department were treated with
infliximab: 18 male, nine females, mean age
40.6 � 13.7 years (range 21–71). The mean duration of pso-
riasis was 17.6 � 9.9 years (range 0.4–40). Twenty-two cases
were of plaque psoriasis, including 14 male and eight female
patients. The mean baseline PASI was 19.0 � 11.4 (range
2.4–46.7). The mean plaque psoriasis baseline PASI was
17.8 � 10.7 (range 2.4–46.7). Most patients received three to
seven infusions. Fourteen patients, including 11 with plaque
psoriasis, strictly adhered to the therapeutic schedule before
14 weeks. In all 14 with least 14 weeks of strict adherence to
therapy, the average PASI score decreased from 18.7 to 2.7 at
the 14th week. The percentage change from baseline in PASI
reached 81% at the week 14. In 11 patients with plaque psori-
asis with at least 14 weeks of strict adherence to therapy, the
average PASI score decreased from 16.7 to 3.7 at the week 14.
The percentage change from baseline in PASI reached 81% at
the week 14 week. In total 37% of patients reached PASI 90
(≥ 90% improvement from baseline), 18% of patients reached
PASI 75 and 22% of patients reached PASI 50. One case aggra-
vated and one did not adhere to the therapeutic schedule
before 14 weeks. Two patients maintained PASI 90 for
10 months and 17 months, respectively. Five patients main-
tained PASI 75 and seven patients, including four with plaque
psoriasis, maintained PASI 50. One patient showed rebound
after 6 months without any treatment. Six cases relapsed,
including five with plaque psoriasis, where the improvement
in PASI score fell below 50% from baseline. None rebound in
3 months. Six of 27 (22%) patients had adverse reactions such
as aggravation, dizziness, shortness of breath, cold sweat,
blood pressure decrease, mild distending head pain, herpes
zoster, slight chest distress, shortness of breath and low-grade
fever. There were no severe adverse reactions. Infliximab has a
good clinical response and is relatively safe in the treatment of
the Chinese patients with psoriasis.
P028Secukinumab clinical outcomes in a tertiary referralcentreO. Jagun, S.T. Cheung, O. Jagun and S.T. CheungThe Royal Wolverhampton NHS Trust, Wolverhampton, U.K.Secukinumab is a fully human monoclonal antibody against
interleukin-17A. Long-term efficacy has been demonstrated in
clinical trials, with up to 76% of patients achieving ≥ 90%
improvement in Psoriasis Area and Severity Index (PASI 90) at
week 52 (Blauvelt A, Reich K, Tsai TF et al. Secukinumab is
superior to ustekinumab in clearing skin of subjects with
moderate-to-severe plaque psoriasis up to 1 year: results from
the CLEAR study. J Am Acad Dermatol 2016;76: 60–9). The
National Institute for Health and Care Excellence (NICE) rec-
ommends secukinumab in patients with severe psoriasis [PASI
and Dermatology Life Quality Index (DLQI) > 10] and in
those with contraindications, intolerance or failed responses to
other systemic therapies. The aim of this study was to evaluate
the appropriateness and efficacy of secukinumab in all the
patients treated in our tertiary referral centre. Patients were
identified from our pharmacy database and data were collected
from electronic patient records and research trial documenta-
tion between December 2013 and March 2017. The PASI and
DLQI scores were extracted at baseline and weeks 12 and
week 52. Sixteen patients were identified 88% (n = 14) of
whom met the criteria for severe psoriasis. Thirteen (81%)
had been on previous systemics, 13% (n = 2) had contraindi-
cations and 31% (n = 5) were intolerant to other systemics.
Seven were clinical trial patients, while nine were nontrial
patients; nine patients were biologic naive while seven had
previous biologics. An average PASI reduction of 80.6% was
observed after 12 weeks and 73.2% after 52 weeks. Of the
data available, 10% of patients achieved PASI 100, 40% PASI
90 and 30% PASI 75 at week 12, while 29% achieved PASI
100 and 43% PASI 75 at week 52. Overall, 90% (n = 10) and
80% (n = 6) of patients achieved the NICE criteria for
response assessment at weeks 12 and week 52, respectively, of
the data available. Our data demonstrate that secukinumab,
despite being more efficacious in biologic-naive patients, is
also effective in treatment-resistant patients who have failed
previous biologics at 1-year. More real-life data are required
to assess longer-term safety and efficacy.
P029Sustained response to adalimumab over multipleyears in patients with plaque psoriasis: analysesfrom the British Association of DermatologistsBiologic Interventions Register (BADBIR)B. Kirby,1 J.-F. Maa,2 T. Festini,2 B. Calimlim2 andO.R. Servın21St Vincent’s University Hospital, Dublin, Ireland and 2AbbVie Inc., North
Chicago, IL, U.S.A.Psoriasis is a life-long chronic disease requiring enduring
treatment. The introduction of biological therapy has greatly
improved psoriasis management, and data on real-world bio-
logics vs. conventional therapy are needed to understand ther-
apy profiles over time. BADBIR, a long-term
pharmacovigilance register, monitors the safety of biologics
and conventional therapy in patients with psoriasis in the U.K.
and Republic of Ireland. The tumour necrosis factor-a inhibi-
tor adalimumab is an approved treatment for moderate-to-
severe plaque psoriasis. Using BADBIR registry data, we
assessed response to adalimumab vs. conventional therapy
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
28 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
87ABSTRACTS
every 6 months through year 3 and then yearly (observed data
through September 2016) in patients with plaque psoriasis.
Patients initiated or switched to a biologic or conventional
therapy within 6 months of registration; patients initiating
conventional therapy had to have Psoriasis Area and Severity
Index (PASI) ≥ 10 and Dermatology Life Quality Index (DLQI)
>10 (no PASI/DLQI requirement for biologics). PASI, Physi-
cian’s Global Assessment (PGA) and DLQI were assessed. In
total 3311 patients treated with adalimumab (baseline mean
age 45 years; 60% men; mean � SD PASI 12.4 � 8.7; mean
DLQI 13.2 � 9.0; mean PGA 3.4 � 1.5) and 4382 treated
with conventional therapy (baseline mean age 44 years; 56%
men; mean PASI 14.9 � 8.1; mean DLQI 15.4 � 6.9; mean
PGA 3.8 � 1.0) were included. Over 6 years, the proportions
of patients with PASI 75, 90 and 100 responses were
significantly greater with adalimumab than with conventional
therapy, with response rates maintained at 71.8–77.5% vs.
37.2–52.2%, P < 0.001; 50.1–53.6% vs. 17.4–31.9%,P < 0.01 and 30.1–33.3% vs. 7.5–15.9%, P < 0.01, respec-
tively. The proportions of patients with PGA 0–1 over 6 years
were also significantly higher in patients treated with
adalimumab vs. conventional therapy, with response rates
maintained at 65.9–71.6% vs. 29.6–40.8%, P < 0.001. Simi-
larly, the proportions of patients with DLQI 0–1 were greater
with adalimumab vs. conventional therapy through year 4
(60.3–67.4% vs. 23.8–31.5%); only 20 patients had DLQI
data beyond year 4. These results demonstrate that adali-
mumab significantly improved the signs and symptoms of pla-
que psoriasis compared with conventional therapy. Moreover,
the clinical and quality-of-life responses to adalimumab in
patients with plaque psoriasis were sustained over multiple
years in this real-world experience.
P030Successful treatment of psoriasis withsecukinumab after ustekinumab in a patient withmultiple sclerosisS. Kaneko,1 H. Oguro2 and E. Morita11Department of Dermatology and 2Department of Neurology, Shimane
University Faculty of Medicine, Izumo, JapanA 49-year-old man had been treated with steroid and vitamin
D3 ointment for psoriasis vulgaris since 25 years of age. He
was diagnosed with multiple sclerosis at 42 years of age. Prior
to treatment, his Psoriasis Area and Severity Index (PASI) was
16.9, and his Expanded Disability Status Scale (EDSS) score
was 2. Psoriasis eruption were cleared after using the steroid
pulse therapy induction to treat multiple sclerosis. After that
treatment, he developed hypertension and diabetes. When
interferon-b was administered as maintenance therapy for
multiple sclerosis, joint pain and psoriatic skin eruptions
occurred. When the patient was 43 years old, therapy with
ustekinumab was introduced, as the other immunosuppressive
therapies were unsuccessful. Although the skin eruptions were
relieved, the joint pain worsened in both hands and feet, and
deterioration was confirmed on X-ray. At 47 years of age, his
EDSS score was 7.5, at which time his therapy was switched
to secukinumab. His psoriatic eruptions were relieved, PASI
became clear, and joint pain was reduced. His C-reactive pro-
tein level, which was initially high, had also decreased.
Although multiple sclerosis is a progressive demyelinating dis-
ease, the EDSS score of 7.5 in our patient did not adversely
deteriorate after the administration of secukinumab. According
to the Group for Research and Assessment of Psoriasis and
Psoriatic Arthritis (GRAPPA) recommendations, the most com-
monly recommended biologics for the treatment of psoriatic
arthritis are the tumour necrosis factor (TNF) inhibitors inflix-
imab and adalimumab. As TNF inhibitors are contraindicated
in patients with multiple sclerosis, ustekinumab was the only
biologic available for this patient before the recent approval of
secukinumab, an interleukin-17A inhibitor. This case demon-
strates the successful administration of ustekinumab, and
secukinumab may have shown effects not only on psoriasis
but also on multiple sclerosis.
P031Development of pulmonary sarcoidosis in a patientwith psoriasis under treatment with ustekinumab:comorbidity or drug-related ‘paradoxical’phenomenon?C. Fotiadou, E. Lazaridou, E. Sotiriou andD. IoannidesFirst Department of Dermatology, Aristotle University Medical School,
Thessaloniki, GreecePsoriasis is a chronic, inflammatory skin disorder with a com-
plex pathophysiology. Psoriasis pathogenesis is mediated by
the activation of both T helper (Th)1 and Th17 lymphocytes.
Sarcoidosis is a granulomatous disease that is also characterized
by Th1/Th17-driven inflammation. Some authors believe that
psoriasis pathogenesis is, in some cases, associated with that
of sarcoidosis, while others have described the paradoxical
induction of certain autoimmune conditions such as sarcoido-
sis after the initiation of psoriasis treatment with antitumour
necrosis factor (anti-TNF)-a biological agents. Here we
describe the case of a 32-year-old man with a 5-year history
of mild psoriasis. During the last year his condition had dete-
riorated (Psoriasis Area and Severity Index 15.2, Dermatology
Life Quality Index 12) and he was treated with ciclosporin
150 mg twice daily. After 6 months with no adequate
response, it was decided to change treatment to ustekinumab
45 mg, an anti-interleukin (IL)-12/23 monoclonal antibody
with an approved dosing regimen for psoriasis. After the first
two injections (0 and 4 weeks) his psoriasis ameliorated
reaching PASI 75, but he presented a thoracic pain and mild
fever (37.2 °C). Chest X-ray and computed tomography
showed bilateral hilar lymphadenopathy with disseminated
nodules in the lungs. Sputum culture and Mantoux test were
negative for Mycobacterium tuberculosis. Bronchoscopy, along with
the histological examination of a representative lesion, con-
firmed the diagnosis of sarcoidosis. The patient stopped ustek-
inumab and started treatment with systemic steroids. This is
one of the very few cases in the literature describing the
development of sarcoidosis after the initiation of psoriasis
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 29
treatment with ustekinumab. Ustekinumab itself was given,
off-label, for the treatment of sarcoidosis. More research and
more experience is needed in order to certify whether sar-
coidosis is a comorbidity of psoriasis or whether ustekinumab
may, in some cases, induce autoimmune diseases such as
sarcoidosis.
P032Factors associated with the choice of the firstbiologic in psoriasis: real-life analysis from thePsobioteq cohortE. Sbidian,1 C. Giboin,2 H. Bachelez,3 C. Paul,4
M. Beylot-Barry,5 A. Dupuy,6 M. Viguier,7 J.-P. Lacour,8 J.-L. Schmutz,9 P. Bravard,10 E. Mah�e,11
N. Beneton,12 L. Misery,13 E. Delaporte,14
P. Modiano,15 S. Barbarot,16 S. R�egnier,17
D. Jullien,18 M.-A. Richard,19 P. Joly,20 F. Tubach2 andO. Chosidow1
1Hopitaux Universitaires Henri Mondor, Cr�eteil, France; 2Hopitaux
Universitaires Piti�e Salpetri�ere, Charles Foix, Paris, France; 3Hopital Saint-
Louis, Paris, France; 4Hopitaux Universitaires de Toulouse, Toulouse, France;5Hopital Saint-Andr�e, Bordeaux, France; 6Centre Hospitalier Universitaire de
Rennes, Rennes, France; 7Hopitaux Universitaires Robert Debr�e, Reims,
France; 8Centre Hospitalier Universitaire de Nice, Nice, France; 9Centre
Hospitalier R�egional Universitaire de Nancy, Nancy, France; 10Groupe
Hospitalier du Havre, Le Havre, France; 11Hopital Victor Dupouy, Argentueil,
France; 12Centre Hospitalier du Mans, Le Mans, France; 13Centre Hospitalier
R�egional Universitaire de Brest, Brest, France; 14Centre Hospitalier R�egional
Universitaire de Lille, Lille, France; 15Groupement des Hopitaux de l’Institut
Catholique de Lille, Lille, France; 16Centre Hospitalier Universitaire de
Nantes, Nantes, France; 17Hopitaux Universitaires Cochin, Paris, France;18Hopital Edouard Herriot, Lyon, France; 19Hopital La Timone, Marseille,
France and 20Rouen University Hospital, Rouen, FranceDecision making is a complex process. The aim of our study
was to assess factors associated with the choice of the first bio-
logical treatment in patients with moderate-to-severe psoriasis.
Data on all patients included in the French prospective, obser-
vational, cohort, Psobioteq, and initiating a first biological
prescription between July 2012 and July 2016 were analysed.
Demographic information and clinical features were collected
during routine clinical assessments by the dermatology team
at the recruiting centres using a standardized case report form.
The primary outcome was the nature of the first biological
treatment. Four groups were identified: adalimumab, etaner-
cept, ustekinumab and infliximab. Factors associated with the
choice of the first biological agent were determined by a
multinomial logistic regression model adjusted on year of
inclusion. The study population included the 830 biologic-
naive patients who initiated a first biological agent. The mean
age was 46.6 � 13.9 years, and 318 patients (38.3%) were
female. The most commonly prescribed biologic was adali-
mumab: 355 (42.8%) patients, then etanercept (n = 247,
29.8%), ustekinumab (n = 194, 23.4%) and infliximab
(n = 34, 4.0%). In the multinomial logistic regression analy-
sis, patients were significantly more likely to receive adali-
mumab if they had severe psoriasis or if they had psoriatic
arthritis compared with etanercept [adjusted odds ratio (aOR)
0.42, 95% confidence interval (CI) 0.16–1.07] and ustek-
inumab (aOR 0.15, 95% CI 0.04–0.52). Patients were signifi-
cantly more likely to receive ustekinumab (aOR 2.39, 95% CI
1.04–5.50) if they had a positive screening for latent tubercu-
losis compared with adalimumab. Younger patients were also
more likely to receive ustekinumab. Patients with chronic
obstructive pulmonary disease were more likely to be pre-
scribed ustekinumab or etanercept compared with adali-
mumab. There was a trend in favour of etanercept
prescription in patients with cardiovascular comorbidities and
metabolic syndrome and in patients with a history of cancer.
In conclusion, we identified patient- and disease-related fac-
tors that have important influence on the choice of the first
biological agent in clinical practice. Clinicians appear to have a
holistic approach to patient characteristics when choosing a
biological agent in psoriasis.
P033The Psoriasis Association as a role model for othersupport groups: how far can (dare) we go?H.H. OonNational Skin Centre, Singapore, SingaporePsoriasis is visible skin disorder with significant psychosocial
impact and burden. The Psoriasis Association is a dermatology
support group formed in 1982. It is run by volunteers com-
prised of patients, relatives, nurses, allied health professionals,
social workers and doctors. Successful activities include the
annual World Psoriasis Day, media campaigns, conventional
talks by doctors, psychologists, group therapy and screening
for comorbidities. Less conservative but equally successful
activities include exercise sessions, art therapy, healthy cook-
ing at a gourmet kitchen, children’s games and creation of
music videos. In 2011, the Eczema Support Group was started,
tapping on the successful model of the Psoriasis Association
with its large patient following, dynamism and strong out-
reach. Acne Awareness Day was a day-long event in 2016
with activities devoted to teen and adult patients with acne
and their caregivers. Interactive games and multidisciplinary
talks incorporating pharmacists and a psychologist were con-
ducted. Key events included a low glycaemic load lunch to
underscore the importance of diet and acne, and a video high-
lighting awareness on acne and the importance of early treat-
ment. Support groups offer a unique experience and fill the
gaps of the traditional model of care of the dermatologist
clinic by viewing skin diseases in a holistic manner where
patient, family, school, workplace and society are closely
intertwined. The successful model of one support group can
propel the development of other support groups in both a lin-
ear and synergistic manner that addresses the whole person
with proven techniques and ideas.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
30 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
89ABSTRACTS
P034Paradoxical psoriasis caused by tumour necrosisfactor inhibitor therapy: a model system to studythe interplay between environmental triggers andgenetic susceptibility?T. Maruthappu,1 A. Connolly,1 S. Mahil,1,2
B. Kirkham,3 P. DiMeglio2 and C. Smith1,21St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Trust,
London, U.K.; 2King’s College London, London, U.K. and 3Department of
Rheumatology, Guy’s and St Thomas’ NHS Trust, London, U.K.Paradoxical psoriasis (PXP) is an uncommon complication of
treatment with tumour necrosis factor inhibitor (TNFi) thera-
pies and can pose a diagnostic and therapeutic challenge. It
occurs in 2.3–5% of patients receiving TNFi therapy irrespec-
tively of the underlying indication and can require cessation
of therapy. To date, the mechanism underlying the develop-
ment of PXP has remained elusive. We report seven patients
(four female, three male, aged 34–43 years) who developed
PXP following treatment with TNFi therapy: adalimumab
(n = 3), infliximab (n = 2) and certolizumab (n = 2). TNFis
were prescribed for a variety of inflammatory conditions:
ankylosing spondylitis (one positive HLA-B27) (n = 2), psori-
atic arthritis with mild scalp psoriasis (n = 2), plaque psoriasis
(n = 1), neurosarcoidosis (n = 1) and inflammatory bowel
disease (n = 1). Six of the seven patients were biologic na€ıve
prior to the initiation of the TNFi. Four of the patients devel-
oped paradoxical palmoplantar pustular psoriasis affecting both
the palms and soles. Of these, one patient developed markedly
hyperkeratotic scalp psoriasis associated with extensive hair
loss. Two patients developed de novo plaque psoriasis of moder-
ate severity, with thin inflammatory plaques predominantly
affecting the and trunk and limbs. Consistently with previously
reported literature, the mean time to onset of PXP was
17 months. Topical therapies had limited efficacy in six of the
seven patients and subsequently the causative TNFi was
stopped. Three were switched to an alternative TNFi, resulting
in the resolution of PXP in one patient and partial improve-
ment in another. Two patients were commenced on ustek-
inumab and gradually improved. The mean time to resolution
was 14 months; however, five of the seven patients have per-
sistent, albeit improving disease. The pathogenic mechanisms
underpinning PXP have remained elusive so far, but a disrup-
tion in cytokine balance mediated by TNF blockade, with dys-
regulated type I interferon signalling, has been reported. No
predisposing factors for PXP, other than the use of TNFis, has
been identified to date, although a genetic component is
widely suspected. Thus, PXP represents an ideal model system
for a proof-of-principle study unravelling the complex mecha-
nistic interplay between a specific environmental trigger, that
is TNFi, genetic susceptibility and immune dysregulation,
namely aberrant type I interferon response. Due to the infre-
quency of the condition, we welcome a multicentre effort to
recruit carefully phenotyped patients with PXP for future
genetic and functional studies.
P035The coexistence of generalized pustular psoriasisand pemphigus foliaceus in a woman with Cushingsyndrome: a case reportA. Kusumawardani,1,2 S.E. Ilona,1,2 D.A. Mira3,4 andSuradi Radiono3,4
1Sebelas Maret University, Surakarta, Indonesia; 2Moewardi Hospital,
Surakarta, Indonesia; 3Gajah Mada University, Yogyakarta, Indonesia and4Sardjito Hospital, Yogyakarta, IndonesiaPsoriasis is a chronic skin disease, which can be associated
with other skin and systemic disease. Bullous skin disease is
one of the skin diseases associated with psoriasis. Coexistence
of generalized pustular psoriasis (GPP) and pemphigus foli-
aceus (PF) is very rare. The contrasting treatment of GPP and
PF in a patient with Cushing syndrome was a major challenge
in this case. A 33-year-old woman complained of new lesions
of erythematous plaques appearing with fever over the previ-
ous 10 days and multiple flaccid bullae. The patient had had
GPP for 1 year and since then she has received methyl pred-
nisolone (MP) and methotrexate. There was no history of sim-
ilar illness in her family. Physical examination demonstrate
signs of Cushing syndrome. Dermatological examination
revealed multiple erythematous plaques, vesicles, pustules and
erosions in an annular shape with scale accompanied by mul-
tiple striae on the anterior and posterior trunk and abdomen.
On the upper extremities, posterior trunk and gluteus were
vesicles and flaccid bullae on erythematous skin. There was no
mucosal involvement or nail abnormalities. Histopathological
examinations using haematoxylin and eosin staining taken
from two different places were both consistent GPP and PF.
Examination of direct immunofluorescence supported PF. The
patient is being treated with MP and ciclosporin. In the first
2 months of therapy the patient relapsed several times during
the tapering off MP. This patient was maintained with an MP
dose of 8 mg per day and ciclosporin 125 mg per day, and
their condition has been controlled for 9 months. GPP and PF
are two very different skin diseases, both clinically and patho-
genetically. Their coexistent clinical expression possibly
happened because of T-cell-dependent chronic immunostimu-
lation and phototherapy. In PF and pemphigus vulgaris, their
specific human leucocyte antigen allele, namely HLA-DRB1,
has been identified, which is also a specific gene in psoriasis.
Systemic corticosteroids are the mainstay of therapy for PF,
but not in the routine management of psoriasis, especially for
PPG. Currently there are no therapy guideline for their coexis-
tence, therefore a strategy for management of corticosteroid
administration is needed.
P036Retrospective audit on psoriasis, assessment andmanagement: National Institute for Health andCare Excellence guideline CG153 within adermatology departmentM. Verma, A. Leong and S. VelangiQueen Elizabeth Hospital Birmingham, Birmingham, U.K.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 31
A retrospective clinical audit was conducted to evaluate the
assessment and management of patients with psoriasis within
a tertiary centre. The data were compared against the U.K.
National Institute for Health and Care Excellence (NICE) ‘Pso-
riasis: assessment and management’ (CG153). The parameters
reviewed included use of validated tools: Psoriasis Area and
Severity Index (PASI), Patient’s Global Assessment, Dermatol-
ogy Life Quality Index (DLQI) and PEST (Psoriasis Epidemio-
logical Screening Tool). The aims were to assess current
clinical practice as measured against the NICE standards with
review of services including rheumatology referral, ultraviolet
(UV)B phototherapy and use of systemic nonbiological treat-
ments. UVA phototherapy and systemic biological treatments
were not assessed. Data were collected from 50 patients via
random selection using data informatics. One patient was
excluded (no psoriasis). A hospital electronic database was
used to collate patient data, which were entered into a Micro-
soft Excel spreadsheet using the Clinical Audit Toolkit (NICE
CG153) for generation of results. Use of Patient’s Global
Assessment had a compliance of 0%. Use of UVB photother-
apy had 53% compliance and nonbiological therapies 62%
compliance. PEST (annual psoriatic arthritis assessment) had
14% compliance. Rheumatology referral and offers of second-
line therapies when phototherapy failed had 100% compli-
ance. PASI and DLQI assessment completion were both 82%,
and Physician’s Global Assessment compliance was 55%. PASI
is currently the most utilized and validated clinical tool to
assess severity in patients with psoriasis. Documentation of
body surface area compliance was 87%, with difficult-to-treat
sites at 64% and recording of systemic upset at 60%. Studies
have shown that use of both PASI and Patient’s Global Assess-
ment simultaneously is redundant. Result analysis and inter-
pretation were processed automatically by the national toolkit
database; however, raw data interpretation led to plausible
rationale for some discrepancies. To increase PASI, PEST and
DLQI compliance with the NICE guidance, we have designed
and implemented a mandatory electronic pro forma that eases
data collection and provides prompts for essential information
for completion within consultations. Outcomes for the project
include a ‘how to assess patients with psoriasis’ template for
consultations, departmental audit presentation and reaudit
after 1 year alongside the NICE update. The British Association
of Dermatologists recommends a central resource for scoring
tools and disease-specific pro formas to assess patients, but
currently there are none. Clinicians will use standard scoring
systems that will allow appropriate classification of patients
and individualized treatment plans. These are crucial in the
management of patients with psoriasis.
P037Role of Thevetia neriifolia in the treatment ofpsoriasis: clinical case reportD. Maryam,1 S. Souad,2 O.S. Charifa3 andS.-B. Rachida1,31Center Anti Poison and Pharmacovigilance of Morocco and 3Faculty of
Medicine and Pharmacy, Mohammed V University, Rabat, Morocco and
2Botanical, Mycology and Environmental Laboratory, Ibn Tofail University,
Kenitra, MoroccoMany pharmaceutical companies have become very interested
in investigating the therapeutic activities of Thevetia neriifolia in
the treatment of various disorders in humans, especially psori-
asis. Thevetia neriifolia belongs to the family Apocynaceae and is
commonly called oleander yellow or lucky nut tree. Thevetia
neriifolia contains a milky sap that can be extracted from either
leaves or seeds. This sap is full of active substances and has
antioxidant and anti-inflammatory properties. In addition, it
may prevent the cell damage caused by psoriasis. We describe
the case of male patient, 31 years old, who lost his parents
and was very affected by their death. Firstly, he developed
erythrodermic psoriasis lesions (psoriasis drops) in the inner
side of both feet. The plaque psoriasis went on to cover most
of the body without fever. His emotional stress was implicated
in the induction of the psoriasis. He has been using topical
steroids since July 2016, with no improvement of the condi-
tion (Arena C, Morin AS, Blanchon T et al. Impact of glucocor-
ticoid-induced adverse events on adherence in patients
receiving long-term systemic glucocorticoid therapy. Br J Der-
matol 2010; 163: 832–7). The patient used the milky sap of
T. neriifolia for 1 month. During this period we noticed a
favourable evolution of his disease. The erythrodermic psoria-
sis lesions started to disappear gradually after 2 weeks of daily
application of T. neriifolia on his skin. The patient is still under
treatment. Through this clinical case report, T. neriifolia can be
considered a potential source in the manufacture of drugs
against psoriasis.
P038Large-scale imputation of killer cellimmunoglobulin-like receptor copy number inpsoriatic arthritisR. Ahn,1 D. Vukcevic,2,3 A. Motyer,2.3 D. Ellinghaus,4
L.C. Tsoi,5 R.P. Nair,5 C. Palmer,6 J. Oksenberg,1
J. Foerster,6 J.T. Elder,5 A. Franke,4 S. Leslie2,3 andW. Liao1
1University of California San Francisco, San Francisco, CA, U.S.A.;2University of Melbourne, Parkville, Australia; 3Murdoch Children’s Research
Institute, Parkville, Australia; 4Kiel University, Kiel, Germany; 5University of
Michigan, Ann Arbor, MI, U.S.A. and 6University of Dundee, Dundee, U.K.Killer cell immunoglobulin-like receptors (KIRs) are known to
regulate innate immune responses via interaction with human
leucocyte antigen (HLA) molecules. KIR genes, including
KIR2DS1 and KIR2DS2, have previously been implicated in pso-
riatic arthritis susceptibility. However, these previous studies
had limited power to detect associations due to their limited
sample size To overcome the expense of directly genotyping
KIR genes, we implemented the KIR*IMP method to impute
KIR copy number from single-nucleotide polymorphisms on
chromosome 19 from a cohort from the University of Califor-
nia San Francisco (UCSF, n = 864) and the PAGE consortium
(n = 9482). Samples had previously been genotyped on either
the Affymetrix Axiom U.K. Biobank chip (UCSF) or the
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
32 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
91ABSTRACTS
Illumina Immunochip (PAGE consortium). Multivariate logistic
regression that accounted for patient ancestry (as revealed by
principal components analysis) and known high-risk HLA
genotypes revealed that KIR2DS4 deletion copy number was
significantly associated with psoriatic arthritis (P = 0.02). We
also found evidence for interaction between KIR2DS4 deletion
copy number and HLA-C1 (P = 0.01). Our study suggests that
future large-scale studies of typed and imputed KIR (both
copy number and alleles) in psoriatic arthritis are warranted
to discover and confirm novel KIR associations.
P039Psoriasis following PD-1 inhibitor therapy: featuresand treatmentP. O’Connor and J.P. DutzUniversity of British Columbia, Vancouver, BC, CanadaPatients with stage IV melanoma have a 1-year survival rate
< 25%. Advances in therapies that harness antitumour immu-
nity by inhibiting immune checkpoints such as programmed
cell death (PD)-1 have revolutionized the treatment of meta-
static melanoma. The cutaneous toxicities of these drugs can
cause substantial morbidity resulting in cessation of treatment.
The safest and most effective treatments for the cutaneous
side-effects of immune checkpoint inhibitors are not known.
Our aim was to review clinician experience and published
data on the features and management of psoriasis in patients
on PD-1 inhibitor therapy. We performed a case review and
structured literature review. We present three cases of palmo-
plantar and small plaque psoriasis occurring during treatment
with the PD-1 inhibitor pembrolizumab for metastatic mela-
noma. In one case the patient responded to pembrolizumab
but failed topical treatment of psoriasis, resulting in temporary
discontinuation of the immunotherapy. Successful treatment
with methotrexate allowed reintroduction of pembrolizumab.
The patient subsequently had progression of her metastatic
disease. Review of published literature revealed that PD-1 inhi-
bitor-related psoriasis can present with multiple morphologies,
with an increased frequency of the palmoplantar pustulosis
and small plaque types. In patients with pre-existing plaque-
type psoriasis a transition to small plaque morphology after
PD-1 inhibition is common. The most frequently reported
treatments are topical corticosteroids and acitretin, with varied
outcomes. Systemic immunosuppressants including methotrex-
ate and tumour necrosis factor-a inhibitors have been used to
treat other PD-1 inhibitor toxicities (colitis, arthritis); we pro-
pose these treatments may be an option for PD-1 inhibitor-
induced psoriasis.
P040Evaluation of body composition in patients withpsoriasis treated with ustekinumabM. Galluzzo,1 S. D’Adamio,1 R. Pastorino,2 L. Bianchi1
and M. Talamonti11Department of Dermatology, University of Rome ‘Tor Vergata’, Rome, Italy
and 2Section of Hygiene, Institute of Public Health, Catholic University of
the Sacred Heart, Rome, Italy
There is evidence that patients with psoriasis have increased
visceral adiposity, which represents not only an energetic
deposit but also an endocrine organ secreting adipocytokines.
The main goal of psoriatic therapies is to control the disease
and its clinical manifestations. The use of biological drugs,
such as antitumour necrosis factor (anti-TNF)-a agents, seems
to associate with an increase in adiposity. In the literature it is
reported that ustekinumab does not increase body mass index
(BMI) in patients with chronic plaque psoriasis, but there are
no studies on changes of the body composition in these
patients. Unfortunately, BMI fails to distinguish body compo-
nents such as fat mass and free fat mass in single individuals.
On the other hand, obesity may influence the therapeutic
approach to psoriasis and the clinical response to treatment. In
fact, adipose tissue may alter the volume of distribution, limit-
ing the efficacy of the drugs. The purpose of this study was to
investigate the body composition in patients with psoriasis
treated with ustekinumab using bioelectrical impedance analy-
sis and to correlate the bioelectrical impedance data with clini-
cal response to treatment. The study population consisted of
73 patients affected by moderate-to-severe chronic plaque pso-
riasis, naive to biological treatment and treated with ustek-
inumab for at least 1 year. All anthropometric measurements,
including weight, height and waist circumference, were col-
lected at baseline, after 6 months of treatment and then after
1 year. For each patient, we evaluated body composition
using bioelectrical impedance analysis and BiaVector analysis.
Linear mixed-effect models for repeated measures were
applied in order to assess the differences in the body composi-
tion from baseline to 6 and 12 months. For each variable of
the body composition, we fit a linear mixed-effect models
where time (baseline, 6 months and 12 months) and con-
founding factors were the explanatory variables. Significant
decrease were found at month 6 for weight (�0.88 kg, P=
0.03), BMI (�0.30 kg m�2, P= 0.03) and fat mass (�1.06,
P= 0.03). Contextually, free fat mass and total body water
showed increases of 1.06 (P= 0.03) and 0.78 (P= 0.02),
respectively. The significant changes from baseline were not
confirmed at month 12. A significant increase was found at
month 12 for body cell mass (2.63, P < 0.001) and phase
angle (0.60, P < 0.001) In addition, a significant increase was
found for intracellular water (2.42, P < 0.001), and a signifi-
cant decrease for extracellular water (�2.37, P < 0.001).
Lastly, considering the response to treatment, we did not find
a difference between the rate of responders and the body
composition. This is the first study to analyse body composi-
tion changes in patients treated with ustekinumab, and in con-
trast with data reported in studies on anti-TNF-a drugs, we
can say that ustekinumab does not increase adipose tissue, and
it appears to improve intracellular hydration. In addition, the
efficacy of the drug does not appear to be correlated with the
patient’s body composition.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 33
P041Characteristics and risk profile of patients withpsoriasis included in the Turkish national registryPSR-TRN. Onsun,1 E.B. Baskan,2 D. Dizman,1 D.B. Ozkaya,3
A.C. Erkılıc,4 G. Ozarmagan5 and M.A. Gurer6
1Bezmi Alem University, Istanbul, Turkey; 2Uludag University, Bursa,
Turkey; 3Bezmi Alem University, Bursa, Turkey; 4Yeditepe University,_Istanbul, Turkey; 5Istanbul University, Istanbul, Turkey and 6Gazi
University, Ankara, TurkeyThe aim of this study was to assess the characteristics and associ-
ated comorbidities of patients with psoriasis in Turkey in a real-
life setting. The psoriatic arthritis registry of Turkey (PSR-TR) is
the only multicentre web-based registry for psoriasis, and was
established in 2006. Detailed data between 2006 and 2017 for
demographics of psoriasis, treatment profiles and comorbidities
were retrieved from PSR-TR web-based records. The median
age of the 8976 patients in the registry was 38.8 years [in-
terquartile range (IQR) 27.3–51.9]; 4492 (50.0%) were female,
6027 (67.1%) were married and 1777 (19.8%) had a university
degree at the time of the first visit. The median body mass index
was 26.8 kg m�2 (IQR 23.2–30.8). Of the 8976 patients in the
registry, 1321 (14.7%) had at least one concomitant disease at
the time of the first visit. The three most commonly reported
concomitant diseases were hypertension (710, 7.9%), diabetes
mellitus (430, 4.8%) and hypercholesterolemia (246, 2.7%).
Of the patients in the registry; 2527 (28–2%) had mild psoriasis
based on Psoriasis Area and Severity Index (PASI) and 1006
(11.2%) had a PASI score ≥ 10. At the first visit, 4536 (50.5%)
had used at least one type treatment and 4440 (49.5%) patients
did not use any type of treatment, or no details were recorded
in the database. During the follow-up visit, if a patient had used
any treatment at any of the follow-up visits, it was accepted as
treatment used during follow-up. During follow-up visits, 3613
(40.3%) used at least one type of treatment, while 5363
(59.7%) patients did not used any type of treatment or no
details were recorded in the database. Overall 4557 (50.8%)
used topical treatment at the first visit and/or any of the follow-
up visits, 824 (9.2%) received phototherapy at the first visit
and/or any of the follow-up visits, and 3343 (37.2%) used at
least one systemic treatment at the first visit and/or any of the
follow-up visits. The most commonly used systemic treatment
was methotrexate (2212, 24.6%). In total 1169 (13.0%) used at
least one biological treatment at the first visit and/or any of the
follow-up visits. Our results showed a similar prevalence of
demographic features and comorbidities to those of patients
with psoriasis.
P042Treatment profile of patients with moderate-to-severe psoriasis included in the Turkish nationalregistry PSR-TRN. Onsun,1 E.B. Baskan,2 D. Dizman,3 D.B. Ozkaya,1
A.C. Erkılıc,4 G. Ozarmagan5 and M.A. G€urer61Bezmi Alem University, Istanbul, Turkey; 2Uludag University, Bursa,
Turkey; 3Bezmi Alem University, Istanbul, Turkey; 4Yeditepe University,
Istanbul, Turkey; 5Istanbul University, Istanbul, Turkey and 6Gazi
University, Ankara, TurkeyThe aim of this study was to assess the treatment profile of
patients with moderate-to-severe psoriasis in Turkey in a real-
life setting. The psoriatic arthritis registry of Turkey (PSR-TR)
is the only multicentre web-based registry for psoriasis,
and was established in 2006. Detailed data between 2006 and
2017 for demographics of psoriasis, treatment profiles and
dermatologist preferences were retrieved from PSR-TR web-
based records. Of the 8976 patients in the registry, 1006
(11.2%) had a Psoriasis Area and Severity Index ≥ 10. At the
first visit, 640 (63.6%) of the patients had received any type
of treatment; however, topical therapy was the preferred ther-
apy in 338 (33.6%) of the patients and all had received topi-
cal therapy at some time during the follow-up. In total 272
(27%) of the patients received at least one systemic treatment
at the first visit, and the rate increased to 55.4% at the follow-
ing visits. Methotrexate was the most common preferred
systemic agent, used in 138 (13.7%), followed by acitretin in
97 (9.6%). Phototherapy was the preferred treatment in 147
(14.6%). At least one biological treatment was prescribed in
116 (11.5%) at the first visit, which increased to 351
(34.9%) at the following visits. Infliximab was the most pre-
scribed biologic, in 42 (4.2%). Our results demonstrate that a
substantial percentage of patients still do not receive the treat-
ment they deserve, and topical therapy is the first choice at
the initial and follow-up visits.
P043An ongoing independent study to monitor theuptake of interleukin-17 inhibitors among U.S.dermatologistsJ. Robinson and L. PriceSpherix Global Insights, Exton, PA, U.S.A.Each quarter, an online survey of approximately 100 derma-
tologists in clinical practice is fielded by an independent mar-
ket research firm, which specializes in tracking biological
uptake in various autoimmune conditions including psoriasis
and psoriatic arthritis. The most recent survey, fielded in May
2017, finds that since the introduction of ixekizumab the per-
centage of biologic-treated patients with psoriasis on an inter-
leukin (IL)-17 inhibitor has doubled, and they currently
account for nearly one in five biologic-treated patients. Despite
the potential for IL-17 class cannibalization, the growth of
ixekizumab and secukinumab over the past year has been pri-
marily at the expense of the established tumour necrosis factor
inhibitors, adalimumab and etanercept. A third IL-17 inhibi-
tor, brodalumab, was approved by the U.S. Food and Drug
Administration (FDA) in February 2017; however, uptake of
this new agent is negligible. One-third of the surveyed derma-
tologists (n = 103) have no intention of ever using bro-
dalumab, primarily due to the product’s associated suicide
risk, black box warning and required risk evaluation and miti-
gation strategies programme. In a head-to-head comparison of
ixekizumab and secukinumab, dermatologists largely view the
two agents as interchangeable. However, among those who
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
34 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
93ABSTRACTS
perceive a difference between the two agents, 78% believe
ixekizumab is superior when asked to compare the two for
‘efficacy in skin clearance’. Twice as many dermatologists also
believe that ixekizumab possesses a faster onset of action, an
attribute important to patients. Secukinumab does hold a per-
ceived advantage over ixekizumab for effectiveness in psoriatic
arthritis, where it is currently the only FDA-approved IL-17
agent available. Future expectations for the IL-17 class are
favourable, with half of the surveyed dermatologists anticipat-
ing an increase in their use of both ixekizumab and secuk-
inumab in the second half of 2017. To what extent the IL-17
inhibitors can grow will be dependent on two leading factors:
competition from recently approved guselkumab, which will
compete for a similar patient type, and restrictions by man-
aged care, which dermatologists note are the greatest barriers
to increased use of these agents.
P044Electronic monitoring of psoriasis outcomes andgoals in practice: development and introduction ofa standard dataset and a digital managementsystemM. Augustin,1 J. Wimmer,2 M. Otten,2 V. Djamei,3
A. Navarini4 and M.A. Radtke21Institute and German Center for Health Services Research in Dermatology
and 2CVderm, University Medical Center of Hamburg, Hamburg, Germany;3Swiss4ward Germany, Hamburg, Germany and 4Department of
Dermatology, University of Z€urich, Z€urich, SwitzerlandOutcomes measurement and treatment goals are major com-
ponents of modern psoriasis management in practice. How-
ever, full electronic monitoring and documentation systems
are rare. The objective of the current project was to develop a
platform of electronic devices for the management of clinical
and patient-reported outcomes in psoriasis, including apps for
smartphones, tablets and clinical electronic records. The sys-
tem needed to be compatible with German drug regulations
and the regional legal framework. A digital patient manage-
ment system was to be integrated. As a methodological basis,
the selection of outcomes instruments was based on a system-
atic literature review involving an interdisciplinary team of
experts and patients. The group was comprised of the German
national conference on psoriasis, representing more than 1000
dermatologists, as well as patient groups nationwide. Major
selection criteria of outcomes were validity, feasibility and
representation of different outcomes areas in practice. Consen-
sus of instruments was achieved by a Delphi process, followed
by a second consensus round on relevant clinical thresholds
and end points. The final set of outcomes was tested in
selected centres for feasibility, patient acceptance and technical
performance. The technical solution was provided by Swis-
s4ward Germany, a technology company for digital solutions
in dermatology. All development steps were cross-validated
with conventional clinical routine data. The electronic out-
comes set included Psoriasis Area and Severity Index, body
surface area, Dermatology Life Quality Index and Patient Bene-
fit Index, as well as patient treatment satisfaction and,
optionally, a grid body surface permitting patients to mark the
body areas affected. Other facultative instruments were
included. For the identification of disease-controlled days, an
electronic diary was developed and validated, which measures
continuous patient-reported data. For each instrument, a series
of electronic documentation systems was developed. Finally, a
solution on the management of outcomes was achieved by
monitoring relevant patient outcomes in an electronic switch-
board, enabling continuous recording of the patient outcomes
and controlling the achievement of predefined treatment out-
comes. In the first testing, the electronic documentation and
management system showed good technical properties and
was well accepted by patients. The patient education tool
markedly increased patient satisfaction and adherence. In con-
clusion, the electronic documentation system and the resulting
digital toolbox are feasible and beneficial technologies for the
improved management of psoriasis in practice. Areas of use
included routine patient records, patient registries and clinical
trials.
P045Real-world data identify reasons for biologicalswitching in patients with psoriasisJ. Robinson and L. PriceSpherix Global Insights, Exton, PA, U.S.A.A retrospective patient chart review of over 1000 patients with
psoriasis was conducted in August 2017 by an independent
healthcare market research firm that specializes in tracking
biological uptake in various autoimmune conditions including
psoriasis and psoriatic arthritis. Over 200 U.S. dermatologists
in clinical practice conducted an in-depth review of patients
they had recently switched from one biological or apremilast
to a different agent. To qualify, patients had to have been
switched to another biological or apremilast within the past
3 months The audit was compliant with the Health Insurance
Portability and Accountability Act and conformed to require-
ments under the Safe Harbor Act. Additionally, participating
dermatologists completed a questionnaire about their practice
and their opinions about the use of biologics and small mole-
cules in psoriasis. These data were integrated with the patient
chart data to uncover differences between reported treatment
approaches and actual patient management. The aim of the
study was to uncover the clinical and nonclinical triggers for
switching between biological therapies. The study further
sought to assess the common characteristics of patients being
treated with apremilast, antitumour necrosis factor (anti-TNF)
agents, interleukin-17 inhibitors, ustekinumab and the most
recently approved agent, guselkumab. The study also overlays
key points in time: time since psoriasis diagnosis, time since
first exposure to biological or apremilast and time on prior
agent before switch. The analysis of the data will be complete
in September 2017. The authors hypothesize the following:
(i) when insurance mandates are the primary reason for the
switch, TNF cycling is more likely; (ii) the use of a non-TNF
biologic is reserved for later lines of therapy and for patients
with more severe disease, as assessed by the combination of
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 35
body surface area affected, comorbid conditions and
Physician’s Global Assessment; (iii) the use of guselkumab will
primarily displace ustekinumab; (iv) the use of industry-spon-
sored patient assistance programmes is more prevalent among
patients switched to recently introduced products; and (v)
most patients treated with apremilast do not have prior expo-
sure to biological agents and, when switching to apremilast
from a biologic, it is commonly the result of the patient’s
desire for an oral agent or in response to a safety concern
with biological treatment.
P046Comanagement with rheumatologists for patientswith psoriatic arthritis receiving treatment with abiological agent or apremilastJ. Robinson and L. PriceSpherix Global Insights, Exton, PA, U.S.A.A retrospective patient chart review of 1008 patients with pso-
riatic arthritis (PsA) who underwent a switch from one bio-
logical agent or apremilast to another biologic within the
most recent 3 months was conducted in March 2017 by an
independent healthcare market research firm. The aim of the
study, which was completed with the collaboration of 200
U.S. rheumatologists, was to understand current practice man-
agement of patients with PsA and the specific clinical and non-
clinical reasons for therapy changes. The audit was compliant
with the Health Insurance Portability and Accountability Act
and was completed by the treating rheumatologist using an
online, secure audit form. In addition to the patient variables
collected, the project also included a survey of the participat-
ing rheumatologists about their practices and their approach
to PsA patient management. Of interest, 72% of the rheuma-
tologists expressed agreement with the statement ‘I wish der-
matologists would refer PsA patients to me sooner than they
typically do’. Upon analysing the patient records, it was
revealed that most of the patients with PsA were originally
referred by primary care physicians, but more than one in five
were referred by dermatologists. Among those referred by
dermatologists, close to one-third had been previously treated
with a biological agent or apremilast. Furthermore, among
those patients previously treated, the vast majority were
switched to a different agent within the first 3 months of see-
ing a rheumatologist. When asked about ongoing comanage-
ment for the patients who were referred by dermatologists, in
two-thirds of the cases, the rheumatologists reported that they
are the primary physician managing the biologic, and in only
about 20% of the cases did they describe the role between the
dermatologist and themselves as equal. When analysing the
reasons for biologic switching, unsurprisingly, a desire for
increased efficacy in the arthritic disease components was the
most common reason. However, in 14% of the cases, rheuma-
tologists made the switch based on a desire for improvements
in skin efficacy, underscoring rheumatologists’ willingness to
manage both aspects of the disease independently of dermatol-
ogy input. When queried about the preference for using a
biologic in PsA that also has an indication in psoriasis, the
group was largely divided, with one-third reporting that they
are less inclined to use agents that do not have a dual indica-
tion, and another one-third claiming this is not important. In
conclusion, the data suggest that once patients are referred
from dermatologists to rheumatologists the management of
biological therapy is likely to be more commonly directed by
the rheumatologist.
P047Investigation of the role of IKKe role in thepathogenesis of psoriasisI. Weimar, L. Iversen and C. JohansenAarhus University Hospital, Aarhus C, DenmarkInterleukin (IL)-17A is known to play an essential role in the
pathogenesis of psoriasis. IjBf was recently demonstrated to
be a key protein in the development of psoriasis by mediating
IL-17A-driven effects. However, the exact molecular mecha-
nism by which IL-17A and IjBf mediate their psoriatic effects
is not fully understood. IKKe (encoded by the IKBKE gene) is
known to be a critical regulator of IL-17A-mediated signalling.
Interestingly, IKKi was recently demonstrated to play an
important role in the recruitment of neutrophils in IL-17A-
induced inflammation. Moreover, IKKi is involved in the regu-
lation of IjBf expression. Thus, the purpose of this study was
to elucidate the role of IKKe in the pathogenesis of psoriasis.
The methods used in this study included culturing of primary
human keratinocytes, small interfering (si)RNA transfection in
order to knockdown IKKe, quantitative polymerase chain reac-
tion, Western blotting, and haematoxylin and eosin staining.
In addition, the imiquimod-induced psoriasis-like skin inflam-
mation model was used. The mRNA expression of IKBKE was
demonstrated to be significantly increased in skin biopsies
obtained from lesional psoriatic skin compared with both
nonlesional psoriatic skin and normal skin from healthy vol-
unteers. Using siRNA to knockdown IKKe in cultured human
keratinocytes treated with IL-17A and/or tumour necrosis fac-
tor-a revealed that IKKe was involved in the regulation of
specific psoriasis-associated genes including CCL20, DEFB4,
NFKBIZ and CXCL1. To explore further IKKe in the pathogenesis
of psoriasis, the imiquimod-induced psoriasis-like skin inflam-
mation model was applied to IKKe-deficient and wild-type
mice. However, IKKe deficiency was not found to reduce imi-
quimod-induced psoriasis-like skin inflammation as measured
by ear thickness, histological evaluation and expression of
specific psoriasis-associated genes. Taken together, our data
show increased IKBKE mRNA expression in psoriatic skin, as
well as involvement of IKKe in the expression of specific pso-
riasis-associated genes in human keratinocytes. This indicates
that IKKe may play a role in the pathogenesis of psoriasis.
However, this was not substantiated by the results obtained
using the imiquimod-induced psoriasis-like skin inflammation
model in genetically modified mice.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
36 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
95ABSTRACTS
P048The interleukin-17A/F heterodimer regulatespsoriasis-associated genes through IjBfT. Bertelsen, C. Johansen and L. IversenDepartment of Dermatology, Aarhus University Hospital, Aarhus C, DenmarkAntagonists of interleukin (IL)-17 have proven to be highly
effective in the treatment of psoriasis; however, the under-
lying molecular mechanisms involved in the pathogenesis of
psoriasis are not fully understood. Recently, we presented evi-
dence that IjBf (encoded by the NFKBIZ gene) is a key regula-
tor in the development of psoriasis through its role in
mediating IL-17A- and IL-17F-driven effects. IL-17A and
IL-17F are both increased in the skin of patients with psoriasis
and can exist as homodimers or heterodimers. Like IL-17A/A
and IL-17F/F, the IL-17A/F heterodimer is produced by a
variety of immune cells and signals through the same recep-
tors. Based on these facts we hypothesized that the IL-17A/F
heterodimer mediates the regulation of psoriasis-associated
genes through IjBf. The aim of this study was to characterize
the role of the IL-17A/F heterodimer in the regulation of
NFKBIZ expression and in the regulation of psoriasis-associated
genes through IjBf. The methods used in this study were the
culturing of normal human keratinocytes from four to six
donors stimulated with IL-17A/F and tumour necrosis factor
(TNF)-a; small interfering (si)RNA transfection targeting IjBfand quantitative polymerase chain reaction. Statistical analysis
testing for normal distribution was conducted, and a two-way
repeated-measures ANOVA or Friedman test was applied accord-
ing to distribution. For multiple comparisons with control
group the Holm–�Sid�ak or Dunn’s method was applied. Proba-
bility of P < 0.05 was regarded as significant. We demon-
strated that stimulation with the IL-17A/F heterodimer
significantly induced NFKBIZ expression in cultured normal
human keratinocytes. IL-17A/F alone or in combination with
TNF-a significantly induced the mRNA expression of NFKBIZ
after 1.5, 3, 6 and 24 h of stimulation. We found that the
IL-17A/F-mediated induction of NFKBIZ mRNA expression
reached its highest level after 1.5 h of stimulation, and that
IL-17A/F combined with TNF-a increased the induction of
NFKBIZ additionally. Furthermore, we investigated the effect of
IL-17A/F, TNF-a and their combination on NFKBIZ expression
at different concentrations of stimuli. At concentrations of 10,
100 and 1000 ng mL�1, IL-17A/F combined with TNF-a sig-
nificantly induced the mRNA expression of NFKBIZ in a dose-
dependent manner. Moreover, silencing IjBf by siRNA
revealed that IjBf is a key regulator of IL-17A/F heterodimer-
inducible psoriasis-associated genes, including DEFB4, S100A7,
CCL20, CXCL8 and CHI3L1. In conclusion, we present IjBf as a
novel key regulator of the IL-17A/F heterodimer-driven effects
in psoriasis. Thus, antagonists to IjBf could potentially pro-
vide a more targeted approach for treating psoriasis, as well as
for treating other inflammatory and immune-mediated dis-
eases for which IL-17-targeting drugs have proven to be
highly effective.
P049The psoriasis-associated interleukin-17A inducesand cooperates with interleukin-36 cytokines tocontrol keratinocyte differentiation and functionC. Pfaff, Y. Marquardt, D. Kluwig, K. Fietkau,B. L€uscher and J. BaronUniklinik RWTH Aachen, Aachen, GermanyPsoriasis is a T helper 17-driven inflammatory disease affecting
a significant proportion of the world population. Although
interleukin (IL)-17A has been identified as a key cytokine in
the pathogenesis of psoriasis, the molecular consequences of
IL-17A signalling are only partially understood. Therefore we
investigated the effects of IL-17A on downstream molecules
and on the formation and functionality of the skin barrier in
human organotypic three-dimensional (3D) skin equivalents.
We used psoriasis models developed with normal human epi-
dermal keratinocytes (NHEKs) and dermal fibroblasts from
psoriatic lesions of patients and control models containing
cells from healthy donors. Stimulation with IL-17A led to a
defective differentiation of keratinocytes in both models. In
agreement with this phenotype, IL-17A interfered with the
expression of genes encoding structural proteins, which are
important for epidermal differentiation. In addition, antimi-
crobial peptides (AMPs), including human b-defensins and
members of the S100 protein family, are induced, resulting in
a strengthening of the chemical barrier. Finally, we observed
that cytokines, including IL-36 family members, were deregu-
lated upon IL-17A stimulation. We speculated that the IL-17A
effects were at least in part mediated by the induction of
IL-36 cytokines in keratinocytes. Functionally similar to
IL-17A, active IL-36 interfered with keratinocyte differentia-
tion in 3D models and induced the expression of genes
encoding different AMPs. The molecular analysis revealed
strong cooperative effects of these two cytokines in activating
target genes dependent on proteolytic processing of IL-36. In
NHEKs and 3D models we could show that IL-36 cytokines
are produced and secreted upon IL-17A stimulation and that
these proteins are unprocessed and therefore almost inactive.
We were able to activate the released IL-36c with the addition
of activated neutrophil supernatants or recombinant neutrophil
elastase. In both approaches we could detect an increased
expression of genes encoding AMPs and IL-36 cytokines. In
addition, active IL-36c can also induce the expression of
IL-17C and seems to be part of a feed-forward loop. This sug-
gests an amplification cycle that involves IL-17, IL-36 and acti-
vating proteases, providing a molecular explanation for a
persistent psoriatic phenotype. In conclusion, we found that
IL-17A disturbed differentiation in control and psoriasis 3D
skin models. The analysis of the downstream consequences
showed that IL-36 cytokines are produced but need to be
activated via neutrophil proteases to enhance the IL-17A
effects in a synergistic manner.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 37
P050Investigation of the efficacy and safety of acitretintreatment in children with pustular psoriasisX. Zhang, J. Liang and C. LiInstitute of Dermatology, Guangzhou Medical University, Guangzhou, ChinaA retrospective study was undertaken in 15 children with pus-
tular psoriasis (nine boys and six girls). Their mean age was
3.4 � 2.9 years (range 5 months to 9 years). The average
duration of disease was 1.0 years. Ten (67%) of our patients
have generalized pustular psoriasis (GPP) (five boys and five
girls), three (20%) have with palmoplantar pustulosis (PPP)
(three boys) and two (13%) have acrodermatitis continua of
Hallopeau (ACH) (one boy and one girl). They received aci-
tretin in doses of 0.6–1.0 mg kg�1 per day for 4–6 weeks,
then a transition dose of 0.2–0.4 mg kg�1 per day for 4–6 weeks and a maintenance dose of 0.2–0.3 mg kg�1 per day.
We defined excellent response as > 90% clearance of the skin
lesions, good response as 60–90% clearance, moderate
response or improvement as 30–60% clearance, and poor
response as < 30% clearance. The initial treatment dose was
0.6–1.0 mg kg�1 per day for 4–6 weeks, followed by transi-
tion to a dose of acitretin of 0.2–0.4 mg kg�1 per day for a
further 4–6 weeks. The acitretin dose was then adjusted
according to the patients’ clinical responses and side-effects. In
five cases of GPP with tonsillitis and fever, we aimed to con-
trol the infection by concomitant short-term therapy with azi-
thromycin 10 mg kg�1 per day for 4 days. The tonsillitis has
improved in 5 days, and the fever decreased in 3 days, with
body temperature reaching the normal range for all of the five
cases within a week. The 10 cases with GPP, three cases with
PPP and one case of ACH (93%,14 of 15) showed good-to-
excellent response, new pustule formation mostly ceased in
3 days and the skin lesion remission started in 5–7 days. The
acitretin therapy resulted in complete resolution of the skin
lesions within 4–6 weeks for all of those cases, and one case
with ACH (7%) resistant to acitretin therapy exhibited moder-
ate response. When the skin lesions had resolved completely
with the disease under control, acitretin was decreased to a
maintenance dose of 0.2–0.3 mg kg�1 per day for around
6 months. However, one patient with GPP had a relapse when
she ceased acitretin by herself because her skin lesion was in
complete remission within 2 months, but retreatment was still
effective. Overall, 80% (12 of 15) of patients had clinical
side-effects, but these were generally mild and transient. The
most frequently reported acitretin treatments in patients with
pustular psoriasis were dry skin (67%, 10 of 15), itching
(27%, four of 15), cheilitis (20%, three of 15) and dry
mouth (7%, one of 15). Side-effects are mainly dose depen-
dent and may be reduced or avoided by using a lower dose of
therapy and performing routine monitoring.
P051Real-world use of fumaric acid esters in psoriasis:results from the British Association ofDermatologists Biologic Interventions Register(BADBIR)K.J. Mason,1 M. Lunt,1 H.J. Hunter,1,2 Z.K. Jabbar-Lopez,3 B. Kirby,4 C.E. Kleyn,1,2 S. Kreppel,2
K. McElhone,1 N.J. Reynolds,5,6 R.B. Warren12 andC.E.M. Griffiths1,2 on behalf of the BADBIR StudyGroup7
1The University of Manchester, Manchester, U.K.; 2Salford Royal NHS
Foundation Trust, Salford, U.K.; 3King’s College London, London, U.K.;4St Vincent’s University Hospital, Dublin, Ireland; 5Newcastle University,
Newcastle upon Tyne, U.K.; 6Newcastle Hospitals NHS Foundation Trust,
Newcastle upon Tyne, U.K. and 7British Association of Dermatologists,
London, U.K.There is a dearth of published data on the real-world use of
fumaric acid esters (FAEs) to treat psoriasis in the U.K. and
Republic of Ireland. The aim of this study was to describe the
survival, effectiveness and safety profile of FAEs in clinical
practice. BADBIR is a web-based pharmacovigilance register of
patients with psoriasis from 156 dermatology centres in the
U.K. and Republic of Ireland exposed to conventional systemic
and/or biological therapies. Biologic-naive patients registering
on FAEs, or who were exposed to them at follow-up, were
included in the analysis. Drug survival was calculated from the
time of initiating FAE to stopping or censor at the last follow-
up, discounting any temporary cessations of 90 days or less.
For effectiveness, baseline Psoriasis Area and Severity Index
(PASI) was defined as a value of 5 or more within 12 months
prior to initiating FAEs; 6- and 12-month PASI values were
identified between 4–8 months and 10–14 months after initi-
ating therapy, respectively. The proportion of patients achiev-
ing ≥ 75% reduction in PASI (PASI 75) at 6 and/or
12 months was calculated. Adverse events (AEs) reported prior
to stopping FAEs were examined, and were coded according
to the Medical Dictionary for Regulatory Activities. Overall
572 patients (median age 43 years; 58% male) with a
prospective exposure to FAEs were identified, of whom 413
(72%) discontinued during follow-up; 484 (85%) patients
initiating FAEs had previous exposure to other systemic thera-
pies. The discontinuation rate of FAE at 12 months was 53%,
with 25% stopping for AEs, 17% for ineffectiveness and 9%
for other reasons. In total 137 patients (24%) were included
in the effectiveness analysis. The median absolute change in
PASI (interquartile range) was �6.6 (�10.2 to �1.7) at
6 months, and �7.7 (�10.9 to �3.7) at 12 months. PASI 75
was achieved by 28% patients at 6 months, 41% at 12 months
and 18% at both 6 and 12 months. In total, 604 AEs were
reported for 306 patients during FAE exposure. The most
common AEs were 152 (25%) gastrointestinal disturbances,
71 (12%) instances of flushing, 63 (10%) lymphocytopenia
and 52 (9%) psoriasis exacerbations (FAE ineffectiveness). In
conclusion, 53% patients discontinued FAEs in the first
12 months, largely due to AEs or ineffectiveness. The most
common AEs were gastrointestinal disturbances and flushing.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
38 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
97ABSTRACTS
Only 21% patients maintained PASI 75 at 6 and 12 months.
These data provide valuable insight for clinicians and patients
considering FAEs for psoriasis.
P052A real-world comparison of effectiveness andsafety outcomes between clinical trial-eligible and-ineligible patients in the British Association ofDermatologists Biologic Interventions Register(BADBIR)K.J. Mason,1 J.N.W.N. Barker,2 C.H. Smith,2
P.J. Hampton,3 M. Lunt,1 K. McElhone,1
R.B. Warren,1,4 Z.Z.N. Yiu,1,4 C.E.M. Griffiths,1,4
A.D. Burden5 and on behalf of the BADBIR StudyGroup6
1The University of Manchester, Manchester, U.K.; 2King’s College London,
London, U.K.; 3Newcastle Hospitals NHS Foundation Trust, Newcastle upon
Tyne, U.K.; 4Salford Royal NHS Foundation Trust, Salford, U.K.; 5Royal
Infirmary of Edinburgh, Edinburgh, U.K. and 6British Association of
Dermatologists, London, U.K.There is preliminary evidence that patients with psoriasis eligi-
ble for clinical trials of biologics are not representative of real-
world patients. The aim of this study was to determine
whether patients enrolled in BADBIR identified as eligible or
ineligible for clinical trials differed in effectiveness and safety
profiles. BADBIR is a web-based pharmacovigilance register of
patients with psoriasis from 156 dermatology centres in the
U.K. and Republic of Ireland exposed to conventional systemic
and/or biological therapies. Patients with at least 6 months of
follow-up who registered on Enbrel (n = 1509), Humira
(n = 4000) or Stelara (n = 1627) were included in the analy-
sis. Eligibility criteria were extracted from phase III trials sub-
mitted for licensing; additional sources (amgentrials.com;
clinicaltrials.gov; clinical study reports; related manuscripts)
were reviewed for eligibility criteria. Baseline Psoriasis Area
and Severity Index (PASI) values (recorded within 6 months
prior to initiating therapy) were subtracted from PASI values
at 12 months (recorded 10–14 months after initiating ther-
apy) to calculate the median absolute change. Incidence rate
ratios (IRRs) were calculated between the eligibility categories
for the total number of serious adverse events (SAEs) reported
within 12 months of initiating therapy. The following cate-
gories were identified: eligible (Enbrel 56%, Humira 56%,
Stelara 46%), ineligible (Enbrel 24%, Humira 7%, Stelara
24%), insufficient baseline PASI (Enbrel 10%, Humira 29%,
Stelara 23%) and missing baseline PASI (Enbrel 10%, Humira
8%, Stelara 7%). The median absolute change in PASI (in-
terquartile range) at 12 months for ineligible patients [Humira
�11.5 (�15.5 to �8.6), Stelara �11.5 (�17.0 to �8.0)] was
significantly smaller than for eligible patients: �14.4 (�19.3
to �10.9) and �14.4 (�18.7 to �11.2), respectively. There
was no significant difference in median absolute change in
PASI for Enbrel patients at 12 months [eligible �10.3 (�14.3
to �6.7), ineligible �10.5 (�14.7 to �6.7)]. Patients with
an insufficient baseline PASI reported a significantly smaller
median absolute change at 12 months than eligible patients.
SAE rates were highest in the ineligible patients, with signifi-
cantly higher IRR than eligible patients: IRR (95% confidence
interval), Enbrel 1.9 (1.4–2.6); Humira 2.0 (1.5–2.6); Stelara2.8 (2.1–3.8). No differences in SAE rates were detected for
ineligible patients in either baseline PASI category when com-
pared with eligible patients. In conclusion, in the first
12 months of treatment in BADBIR, patients ineligible for
clinical trials for Enbrel, Humira and Stelara had lower effec-
tiveness and higher SAE rates than those who would be eligi-
ble. Thus, clinical trial findings are not representative of real-
world patients.
P053Guselkumab treatment provided higher frequencyof complete skin clearance compared withadalimumab treatment among patients withmoderate-to-severe plaque psoriasisP. Foley,1 M. Song,2 Y.-K. Shen,2 Y. You,2 Y. Wasfi2
and C.E.M. Griffiths31The University of Melbourne, St Vincent’s Hospital, Melbourne and Skin &
Cancer Foundation Inc., Carlton, Australia; 2Janssen Research & Development,
LLC, Spring House, PA, U.S.A. and 3The University of Manchester,
Manchester Academic Health Science Centre, Manchester, U.K.The rates of complete skin clearance associated with guselku-
mab vs. placebo and adalimumab treatment were assessed in
the VOYAGE 1 and VOYAGE 2 clinical trials. In the phase III,
randomized, double-blind, placebo/active comparator-con-
trolled VOYAGE 1 (n = 837) and VOYAGE 2 (n = 992) trials,
patients (≥ 18 years) had plaque psoriasis for ≥ 6 months,
Investigator’s Global Assessment (IGA) scores ≥ 3, Psoriasis
Area and Severity Index (PASI) scores ≥ 12 and ≥ 10% body
surface area involvement, and were candidates for systemic
treatment or phototherapy. Patients were randomized to
guselkumab 100 mg at weeks 0, 4 and 12 than every
8 weeks; placebo at weeks 0, 4 and 12 followed by guselku-
mab 100 mg at weeks 16 and 20 then every 8 weeks; or adal-
imumab 80 mg at week 0, 40 mg at week 1 and 40 mg
every 2 weeks through week 47 (VOYAGE 1) or week 23
(VOYAGE 2). Pooled efficacy, assessed by 100% improvement
in PASI (PASI 100), IGA 0 and Psoriasis Symptoms and Signs
Diary (PSSD) symptoms/signs = 0 (absent signs/symptoms)
from VOYAGE 1 and VOYAGE 2 through week 24 are pre-
sented in this analysis. As early as week 8, a higher proportion
of guselkumab-treated patients achieved PASI 100, IGA 0 and
PSSD signs and symptom scores of 0 vs. placebo. At week 16,
a notable separation between the proportions of patients
achieving these end points in the guselkumab and adalimumab
groups was observed, and the difference was significant at
week 24. In conclusion, guselkumab provided higher rates of
skin clearance, as assessed by PASI 100, IGA 0 and PSSD
symptoms/signs = 0 responses, than adalimumab through
week 24 and placebo at week 16.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 39
P054Antibodies to guselkumab are not associated withreduction in clinical response or development ofinjection-site reactions in patients with moderate-to-severe plaque psoriasisY. Zhu,1 J.C. Marini,1 Y. Wasfi,1 B. Randazzo,1,2
Y.-K. Shen,1 S. Li1 and H. Zhou1
1Janssen Research & Development, LLC, Spring House, PA, U.S.A. and2Department of Dermatology, University of Pennsylvania School of Medicine,
Philadelphia, PA, U.S.A.The aim of this study was to assess the immunogenicity of
guselkumab, an anti-interleukin-23 monoclonal antibody, and
its association with pharmacokinetics (PK), efficacy and injec-
tion-site reactions (ISRs) in patients with moderate-to-severe
plaque psoriasis. In two pivotal phase III studies (VOYAGE 1
and 2, with identical study designs through week 24), patients
were randomized to receive subcutaneous administrations of
guselkumab 100 mg (weeks 0 and 4 then every 8 weeks;
n = 825 total); placebo then guselkumab (n = 422 total) or
adalimumab (n = 582 total). Serum samples were collected at
selected time points up to week 48. Antidrug antibodies
(ADAs) against guselkumab were detected using a validated,
sensitive and drug-tolerant electrochemiluminescence
immunoassay method. Serum guselkumab concentrations (sys-
temic exposure), Investigator’s Global Assessment (IGA) and
Psoriasis Area and Severity Index (PASI) responses and ISRs
were evaluated as PK, efficacy and safety end points, respec-
tively. Of 1361 patients who received guselkumab and had
post-treatment serum samples evaluable for ADA, the overall
incidence of ADA up to week 48 was 6.1% (n = 83), with
predominantly low titres (≤ 1 : 160). Only seven of 83
patients had antibodies that were able to neutralize the bioac-
tivity of guselkumab in vitro. No apparent impact of ADAs on
systemic exposure was observed between ADA-positive
and -negative patients (between-patient comparison), before
and after the development of ADA (within-patient compar-
ison), or by the time (sooner or later) when ADAs were
detected. Of the 58 ADA-positive patients who were evaluable
for the effect of ADA on systemic exposure, 21 had numeri-
cally lower, 25 had numerically higher and 12 had numeri-
cally similar serum guselkumab concentrations after the
formation of ADAs. The development of ADAs was not associ-
ated with a reduction in efficacy. In patients randomized to
guselkumab with available data, 48 (89%) of 54 ADA-positive
patients and 637 (83.3%) of 765 ADA-negative patients
achieved IGA 0 or 1 at week 28. Only six (1.5%) of 388
guselkumab injections in ADA-positive patients and 41 (0.7%)
of 6118 guselkumab injections in ADA-negative patients were
associated with ISRs. In conclusion, following subcutaneous
administrations of guselkumab in patients with moderate-to-severe
plaque psoriasis, the incidence of ADAs was low. The develop-
ment of ADAs to guselkumab was not associated with reductions
in systemic exposure or efficacy, or development of ISRs.
P055Psoriasis Longitudinal Assessment and Registry(PSOLAR): description of demographic data fromthe Greek population upon full enrolmentV. Chasapi,1 C. Antoniou,2 D. Rigopoulos,3
A. Roussaki-Schulze,4 D. Ioannides,5 I. Bassukas,6
W. Langholff7 and E. Soura81State Clinic of Dermatology-Venereology, ‘Andreas Sygros Hospital, Athens,
Greece; 21st Department of Dermatology-Venereology, Medical School,
National and Kapodistrian University of Athens, ‘Andreas Sygros Hospital’,
Athens, Greece; 32nd Department of Dermatology Venereology, Medical
School, National and Kapodistrian University of Athens, Αttikon GeneralUniversity Hospital, Athens, Greece; 4Department of Dermatology-
Venereology, University of Thessaly, University General Hospital Larissa,
Placebo Guselkumab Adalimumab
Patients randomized at week 0 422 825 582
Week 8PASI 100 1/422 (0.2%) 84/825 (10.2%) 46/582 (7.9%)
IGA 0 1/422 (0.2%) 143/825 (17.3%) 67/582 (11.5%)PSSD 0
Symptoms 0 80/658(12.2%) 29/473(6.1%)Signs 0 44/659(6.7%) 16/475(3.4%)
Week 16PASI 100 3/422 (0.7%) 292/825 (35.4%) 108/582 (18.6%)
IGA 0 4/422 (0.9%) 372/825 (45.1%) 159/582 (27.3%)PSSD 0
Symptoms 1/327 (0.3%) 179/658 (27.2%); P < 0.001 75/473(15.9%); P < 0.001Signs 0 136/659 (20.6%); P < 0.001 53/475 (11.2%); P < 0.001
Week 24PASI 100 – 365/825 (44.2%) 149/582 (25.6%)
IGA 0 – 430/825 (52.1%) 176/582 (30.2%)PSSD 0 –Symptoms – 234/658 (35.6%) 104/473 (22.0%); P < 0.001Signs – 187/659 (28.4%) 74/475 (15.6%); P < 0.001
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
40 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
99ABSTRACTS
Larissa, Greece; 51st Department of Dermatology, Aristotle University,
Thessaloniki, Greece; 6Department of Dermatology Venereology, Faculty of
Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece;7Janssen Research & Development, LLC, Spring House, PA, U.S.A. and8Jan-Cil Greece, Athens, GreeceThe aim of this study was to report the baseline demographics
and clinical characteristics of Greek participants enrolled in
PSOLAR. PSOLAR is a multicentre, prospective, longitudinal,
observational study designed to follow patients with psoriasis
≥ 18 years of age, currently receiving or candidates to receive
systemic therapies for psoriasis, for ≥ 8 years. The study gath-
ers information from academic and community settings to
generate real-world data regarding patients with psoriasis and
their respective treatments. Such data include baseline demo-
graphics, medical and family history, economic and social
status, adverse events, disease activity, quality of life and inter-
val therapies (evaluated every 6 months). As of 23 August
2014, PSOLAR had enrolled 10 093 patients from North
America, Latin America and Europe. Greece recruited 121
patients, with a patient retention rate of 71.9% since the time
of enrolment. Baseline characteristics for the Greek subpopula-
tion are mean age 45.4 years (median 43.0), with 47.5% of
patients aged ≥ 45 years and 65.3% male. At enrolment
94.2% of patients presented with plaque-type psoriasis, with a
mean Physician’s Global Assessment (PGA) score of 2 � 1.4;
43.3% of patients presented with a PGA score ≥ 3. The mean
duration of psoriasis since diagnosis was 13.7 � 9.8 years,
and 11.6% of patients reported psoriatic arthritis diagnosed by
a joint specialist. The mean body mass index was
29.3 � 5.3 kg m�2, with 74.6% being overweight or obese.
Overall 66.1% and 56.7% of patients reported current use of
alcohol and tobacco, respectively, and 18.2%, 6.6% and
12.4% of patients presented with hypertension, type 2 dia-
betes and hyperlipidaemia, respectively. The mean affected
body surface area and PGA score at peak disease activity were
46.9 � 24.4% and 3.4 � 0.9, respectively, and 33.9% of
patients were receiving systemic therapy at the time of peak
disease activity (16.9% were receiving ciclosporin, 3.4%
methotrexate, 3.4% adalimumab, 3.4% etanercept and 6.8%
infliximab). At the time of enrolment, 82.6% of patients had
received treatment with a biological agent at some point, with
1.7% having received four, 9.1% three, 19.8% two and 52.1%
one. Other treatments included topical therapy (96.7% topical
corticosteroids), phototherapy (25.6%), retinoids (38%),
ciclosporin (67.8%) and methotrexate (28.1%). The clinical,
baseline and historical features for the Greek subset of PSOLAR
patients were as expected for a moderate-to-severe psoriasis
population. Although 74.6% of patients were overweight or
obese, cardiovascular risk factors was reported only in few. In
addition, most patients had received at least one biological or
systemic treatment prior to the time of enrolment, but only
33.9% were receiving systemic treatment at the time of peak
disease activity.
P056Short-term reasons for withdrawal, and safety ofapremilast as a monotherapy and combinationtherapy for psoriasis in clinical practice comparedwith clinical trials: a multicentre retrospectivestudyA. Ighani,1 J.R. Georgakopoulos,2 N.H. Shear,3,4,5
S. Walsh34,5 and J. Yeung3,4,5,61Faculty of Medicine, University of Toronto, Toronto, ON, Canada;2Schulich School of Medicine and Dentistry, Western University, London,
ON, Canada; 3Division of Dermatology, Department of Medicine, University
of Toronto, Toronto, ON, Canada; 4Sunnybrook Health Sciences Centre,
Toronto, ON, Canada; 5Women’s College Hospital, Toronto, ON, Canada
and 6Probity Medical Research Inc., Waterloo, ON, CanadaApremilast is an oral phosphodiesterase 4 inhibitor approved
for the treatment of plaque psoriasis. The safety profile of this
new drug is primarily limited to data published in randomized
controlled trials (RCTs). The objective of our study was to
estimate the real-world safety and incidence of adverse events
(AEs) leading to withdrawal of apremilast in the treatment of
psoriasis, and to compare these findings with RCT results. A
multicentre retrospective chart review was conducted, which
captured all patients treated with apremilast from November
2014 to July 2017. Patients were permitted to use concurrent
therapies with apremilast. Outcome measurements included
the proportion of patients reporting at least AE and the inci-
dence proportion of AEs leading to withdrawal while taking
apremilast during the first 16 weeks of treatment. Real-world
data were compared with RCT data using Pearson’s v2-test(P ≤ 0.01 considered significant). After screening, 208
patients were included in the analysis. A smaller proportion of
real-world patients experienced at least one AE compared with
RCT patients (real world 122 of 208, 58.7%; RCT 573 of
832, 68.9%; P= 0.005). A greater proportion of real-world
patients discontinued apremilast due to AEs compared with
RCT patients (real world 39 of 208, 18.8%; RCT 44 of 832,
5.3%; P < 0.001). Patients who discontinued treatment due to
AEs reported experiencing an average of 2.1 � 1.2 AEs lead-
ing to withdrawal (range one to five). Of the 122 patients
who experienced an AE during the first 16 weeks of treat-
ment, 32.0% went on to withdraw from treatment due to
AEs, and the average time elapsed before withdrawal was
1.7 � 1.0 months. The most commonly reported AEs leading
to withdrawal included diarrhoea (11 of 208, 5.3%), nausea
(10 of 208, 4.8%), headache (nine of 208, 4.3%), nonspecific
gastrointestinal symptoms (seven of 208, 3.4%), abdominal
pain (five of 208, 2.4%), fatigue (four of 208, 1.9%) and
allergic reaction (three of 208, 1.4%). There were no reports
of tuberculosis reactivation or onset of malignancy leading to
withdrawal. In summary, apremilast is generally a safe medi-
cation for the treatment of psoriasis in the real-world setting,
with AEs being reported in similar proportions to RCTs. How-
ever, the proportion of AEs associated with withdrawal in
clinical practice is greater than that reported in RCTs. The
retrospective nature of the study limits the generalizability of
the findings.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 41
P057A comparison of apremilast monotherapy andcombination therapy for plaque psoriasis in clinicalpractice: a multicentre retrospective studyA. Ighani,1 J.R. Georgakopoulos,2 S. Walsh,3,4,5
N.H. Shear34,5 and J. Yeung3,4,5,61Faculty of Medicine, University of Toronto, Toronto, ON, Canada;2Schulich School of Medicine and Dentistry, Western University, London,
ON, Canada; 3Division of Dermatology, Department of Medicine, University
of Toronto, Toronto, ON, Canada; 4Sunnybrook Health Sciences Centre,
Toronto, ON, Canada; 5Women’s College Hospital, Toronto, ON, Canada
and 6Probity Medical Research Inc., Waterloo, ON, CanadaApremilast is a novel, oral drug approved for the treatment of
moderate-to-severe plaque psoriasis as a monotherapy. In clin-
ical practice, it is also used in combination with other biologi-
cal and systemic agents to manage residual plaque psoriasis
that cannot be adequately controlled with one agent alone.
Here we compare the efficacy and safety of apremilast
monotherapy and combination therapy in the real-world set-
ting. A multicentre retrospective chart review was conducted.
Efficacy was measured as the proportion of patients achieving
≥ 75% reduction from baseline Psoriasis Area and Severity
Index score (PASI 75) or a Physician’s Global Assessment
(PGA) score of 0 (clear) or 1 (almost clear) at 16 weeks.
Baseline PASI scores reported for patients on combination
therapy were collected before the onset of apremilast therapy,
not the onset of concurrent systemic therapy. Safety was mea-
sured as the proportion of patients reporting at least adverse
event (AE) at 16 weeks. Binary logistic regression was used to
assess the association of monotherapy and combination ther-
apy with efficacy and safety outcomes (P ≤ 0.05 considered
statistically significant). A total of 296 charts were screened,
and 148 patients were included for analysis. The apremilast
combination therapy cohort (89 of 148, 60.1%) and
monotherapy cohort (59 of 148, 39.9%) showed similar effi-
cacy and safety outcomes. For efficacy, 44% of monotherapy
patients (26 of 59) and 37% of combination therapy patients
(33 of 89) achieved PASI 75 or PGA 0/1 (P = 0.40). For
safety, 63% of monotherapy patients (37 of 59) and 62% of
combination therapy patients (55 of 89) experienced at least
one AE (P = 0.91). Commonly reported adverse events
included headache (monotherapy 24%, combination therapy
12%; P= 0.075), diarrhoea (monotherapy 15%, combination
therapy 17%; P = 0.80), nausea (monotherapy 19%, combi-
nation therapy 11%; P = 0.21) and weight loss (monotherapy
7%, combination therapy 10%; P = 0.49). In conclusion,
apremilast results in clinically significant reduction of chronic
plaque psoriasis, with primarily mild-to-moderate AEs, as both
a monotherapy and combination therapy in the real world.
Limitations of the project include the retrospective nature of
the study. Based on these findings, physicians may consider
using apremilast as a monotherapy to control chronic plaque
psoriasis or as a combination therapy to manage residual pla-
que psoriasis that is not adequately controlled with another
biological or systemic agent alone.
P058An evaluation of the quality of life, treatments andresources available for patients with psoriasis inCanada: a comparison of biologic and nonbiologicusersA. Ighani1 and M.F. Manolson2,31Faculty of Medicine, University of Toronto, Toronto, ON, Canada;2Canadian Association of Psoriasis Patients, Ottawa, ON, Canada and3University of Toronto, Toronto, ON, CanadaThere is a need to update studies analysing Canadians with
psoriasis, given the introduction of new biological treatments.
Here we evaluate the quality of life, treatments and resources
available for patients with psoriasis using biologics or nonbio-
logics as treatment modalities. An online survey, conducted
from July to September 2016, used the following inclusion
criteria: patients with moderate-to-severe psoriasis on one of
the following treatments: biologic, biosimilar, methotrexate,
ciclosporin, apremilast or phototherapy. Additional criteria for
nonbiologic users included psoriasis covering ≥ 10% of body
or psoriasis on the feet, hands, face or genitals. In total 343
patients (218 biologic users and 125 nonbiologic users) were
included. Overall 84% of nonbiologic users were aware of
biologics, and when evaluating various blinded biological
treatments, 45% of nonbiologic users selected blinded ustek-
inumab as their preferred treatment. More biologic users were
satisfied with their treatment (80%) than nonbiologic users
(48%). Regarding quality of life, 41% of biologic users stated
they felt their best when it came to their psoriasis compared
with 25% of nonbiologic users. More ustekinumab users
(70%) than adalimumab users (28%) said they felt their best
regarding their psoriasis, although adalimumab was more
widely used. In terms of patient resources, 77% of patients
selected websites and 73% selected in-person information as
one of their top five preferred resources. Facebook and Twitter
were least preferred. Only 28% of biologic users compared
with 13% of nonbiologic users mentioned healthcare profes-
sional advice as a resource. More nonbiologic users preferred
websites, online forums and Facebook compared with biologic
users. In conclusion, users of biologics were more satisfied
with their treatment and experienced a more positive impact
on life compared with nonbiologic users. Of the available bio-
logics, blinded ustekinumab was most preferred. Patients pre-
ferred websites and in-person information over social media
(Facebook/Twitter) as resources for psoriasis information.
P059Identification of promising biomarkers to predicttherapeutic response to biologics in psoriasisA. Medeiros,1 L. Grine,1 M. Van Gele,1 P. Spuls2 andJ. Lambert11Ghent University Hospital, Ghent, Belgium and 2Academic Medical Center,
Amsterdam, the NetherlandsBiologics are renowned for their effectiveness, but are used as
the last treatment option for moderate-to-severe psoriasis due
to their costs. Currently, we lack guidelines on how to stratify
patients, leading to treatment failure due to unresponsiveness.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
42 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
101ABSTRACTS
This trial and error is not only frustrating for the patient and
doctor, but is a costly matter as well. Here we report the pre-
liminary results on the identification of biomarkers predicting
the therapeutic response to adalimumab and ustekinumab.
Furthermore, we assessed the robustness of mRNA and pro-
teins as biomarkers. Based on the literature, we selected poten-
tial candidates. Patients were recruited at a university hospital
for treatment with either adalimumab or ustekinumab. Blood
was sampled before the first injection and Psoriasis Area and
Severity Index (PASI) was assessed prior to and 6 months after
treatment (DPASI). mRNA markers were measured with
reverse-transcriptase polymerase chain reaction in whole
blood, and protein markers with Luminex and enzyme-linked
immunosorbent assay in serum. Patients were categorized into
responders (DPASI ≥ 90) and nonresponders (DPASI ≤ 75).
Out of 38 potential mRNA markers, we found a significant
differential expression for IL23R, which was lower in non-
responders to ustekinumab, and for VEGF and GOT2, which
were lower and higher, respectively, in nonresponders to adal-
imumab. At the protein level, 14 markers were investigated.
Factor VII correlated significantly with DPASI in ustekinumab-
treated patients, although there was no significant difference
between nonresponders and responders. For adalimumab, a
significant correlation was found for leptin and interleukin-6
with DPASI. Moreover, both proteins were seen in signifi-
cantly higher levels in the nonresponders. In hindsight, practi-
cal and technical evaluation of the robustness of mRNA and
protein showed that the latter was more convenient. Although
this study pilot is based on a small sample size, we provide
evidence that proteins are more promising than mRNA as
biomarkers, and that it is possible to stratify patients for adali-
mumab or ustekinumab. With the arrival of new biologics,
predictive biomarkers are expedient, warranting further inves-
tigation.
P060Evaluation of carcinogenic risk of psoralen–ultraviolet A (PUVA) vs. retinoid–PUVA in patientswith psoriasisH. Mashaly,1 M. Fathy,1 S. Hamdy1 and O. Shaker21Dermatology Department and 2Medical Biochemistry Department, Faculty of
Medicine, Cairo University, Cairo, EgyptPhotochemotherapy with psoralen–ultraviolet A (PUVA) is one
of the classic treatment modalities for psoriasis. Adding reti-
noids in the form of Re-PUVA is hypothesized to reduce the
possible carcinogenic potential of PUVA. 8-Oxoguanine is
among the most mutagenic oxidative DNA modifiers and
induces replication errors. Our aim was to evaluate the possi-
ble carcinogenic protective effect of adding retinoids to PUVA
in patients with psoriasis. A prospective, randomized, con-
trolled study was performed including 20 patients with psori-
asis who were then randomly divided into two groups: group
A received PUVA therapy and group B received Re-PUVA ther-
apy. Each of the 20 patients received 30 sessions of PUVA
photochemotherapy. Patients from Group B received additional
oral retinoids 2 weeks prior to the start of sessions and until
the end of the PUVA sessions. Serum samples were taken from
each of the 20 patients, before and after the last PUVA session,
and were used to measure the 8-oxoguanine level. A signifi-
cant drop in the Psoriasis Area and Severity Index score was
detected in both groups. However, onset of clinical response
was significantly earlier in the Re-PUVA group (P = 0.037),
together with a significantly lower cumulative dose of UVA
(P= 0.002). A rise of serum level of 8-oxoguanine was
noticed in patients with psoriasis following PUVA therapy,
while a drop of serum level of 8-oxoguanine was noticed fol-
lowing Re-PUVA therapy. Comparing the change of serum
levels of 8-oxoguanine in patients receiving PUVA vs. Re-
PUVA showed a more significant drop of 8-oxoguanine in the
patients receiving Re-PUVA (P= 0.023). Re-PUVA was able to
achieve the same clinical response as PUVA in patients with
psoriasis, but with an earlier onset of clinical response, less
UVA cumulative dose, less DNA damage in the serum, and
hence less carcinogenic potential.
P061Successful treatment of recalcitrant hyperkeratoticpalmoplantar psoriasis with itolizumab: a caseseries of three patientsU. Chakravadhanula1 and B.K. Jha21Vaikhan Hospital, Hyderabad, India and 2Medical Affairs, Biocon Ltd,
Bangalore, IndiaPalmoplantar psoriasis (PP) is a chronic inflammatory skin dis-
ease that is associated with distressful quality of life. The
prevalence of chronic plaque psoriasis in different populations
is 1–3%, whereas PP accounts for 3–4% of all cases of psoria-
sis in most studies. We present a case series of three patients
with PP that responded remarkably to itolizumab. Itolizumab
(Alzumab�) is a novel humanized monoclonal antibody
approved for moderate-to-severe chronic plaque psoriasis. It
downregulates T-cell proliferation induced by activated leuco-
cyte cell adhesion molecules by binding to the extracellular
scavenger receptor cysteine-rich distal domain 1 of CD6 (Kru-
pashankar DS, Dogra S, Kura M et al. Efficacy and safety of ito-
lizumab, a novel anti-CD6 monoclonal antibody, in patients
with moderate to severe chronic plaque psoriasis: results of a
double-blind, randomized, placebo-controlled, phase-III study.
J Am Acad Dermatol 2014; 71: 484–92). Case 1, a 22-year-old
man, presented with a history of localized hyperkeratotic plan-
tar psoriasis with toenail involvement for 2 years. Case 2 is a
42-year-old man with both palms affected for 3 years. It is
essential to mention that the patient did not respond to five
doses of secukinumab (anti-interleukin-17A). Case 3 is a 63-
year-old man who presented with severe palmoplantar
hyperkeratosis, fissuring and 100% involvement of the soles
including the nails. Due to failure of available treatment
modalities, all three patients were screened for infection, neo-
plasm and autoimmunity, which were negative in all cases.
They were started on itolizumab at a dose of 1.6 mg kg�1 (in
250 mL of normal saline over 3 h) fortnightly followed by
maintenance phase of three 4-weekly infusions. All patients
achieved 75% improvement in the Palmoplantar Psoriasis Area
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 43
Severity Index after the seventh infusion. The quality of life
significantly improved in all patients. Needless to say, only a
small area of the body is affected in PP or psoriasis of the
palms and soles; however, the symptoms lead to a distressful
and disabling quality of life due to the condition being diffi-
cult to treat. In cases where conventional therapies have failed,
published studies demonstrate that noncytokine biologics,
which act upstream of T-cell proliferation, have been effective
in treating PP; these include alefacept and efalizumab (Lior S,
Grigory K, Pnina S et al. Therapeutic hotline. Alefacept in the
treatment of hyperkeratotic palmoplantar psoriasis. Dermatol Ther
2010; 23: 556–60). In consonance with the efficacy profile of
other upstream acting biologics, namely alefacept and efal-
izumab, itolizumab also resulted in a remarkable response to
PP in the present cases. It can be postulated that itolizumab
immunomodulates the downstream cytokine infiltration in PP
without inhibiting the constitutive expression of lymphocytes,
and thus has a better safety profile. Thus, itolizumab may be a
safe and efficacious treatment option in PP, a difficult-to-treat
variant of psoriasis.
P062Systemic therapy and the risk of nonmelanomaskin cancer among patients in the PsoriasisLongitudinal Assessment and RegistryR. DeShazo,1 R. Soltani-Arabshahi,2 S. Krishnasamy,1
C. Galindo,3 W. Langholff,4 R. Langley,5 S. Kalia,6
S. Fakharzadeh,3 K. Goyal,3 M. St�ahle,7
B. Srivastava3 and G.G. Krueger1
1University of Utah, Salt Lake City, UT, U.S.A.; 2Cleveland Clinic,
Cleveland, OH, U.S.A.; 3Janssen Scientific Affairs, LLC, Spring House, PA,
U.S.A.; 4Janssen Research & Development, LLC, Spring House, PA, U.S.A.;5Dalhousie University, Halifax, NS, Canada; 6University of British
Columbia, Vancouver, BC, Canada and 7Karolinska Institutet, Stockholm,
SwedenPsoriasis is associated with increased risk of nonmelanoma
skin cancer (NMSC), including basal cell carcinoma (BCC) and
squamous cell carcinoma (SCC). Our aim was to determine
the effect of biological therapy on NMSC risk among patients
in PSOLAR, a prospective psoriasis registry for patients eligible
to receive systemic treatment. Data extracted from 23 August
2015 were included. We defined a study population of 6782
PSOLAR patients without a history of NMSC at enrolment who
were prevalent or incident users of biologics (n = 6350) or
methotrexate (MTX, n = 432). The biologics cohort included
infliximab (IFX), etanercept (ETN), adalimumab (ADA) and
ustekinumab (UST). Subcohorts of pooled patients receiving
tumour necrosis factor inhibitors (TNFis; IFX, ETN and ADA;
n = 3727) and UST (n = 2623) patients were also defined for
the secondary objective. Switching of study therapies was
allowed; events falling within any 91-day overlap period were
attributed to both therapies. Incidence rates (IRs) for NMSC
were calculated, and Cox proportional hazard models (using
MTX as the reference) were used to estimate hazard ratios
(HRs) adjusted by covariates relevant to NMSC risk. The treat-
ment cohorts were generally comparable for most baseline
characteristics. Seventy-two new diagnoses of NMSC were
identified [IR 0.37, 95% confidence interval (CI) 0.30–0.47].The IRs and confidence intervals for NMSC, SCC and BCC are
displayed in Table 1a, and hazard ratios by NMSC type are
displayed in Table1b. Biological therapy did not alter the risk
of NMSC. In the secondary analysis, TNFis did not alter the
risk of incident NMSC or BCC compared with MTX, whereas
UST showed significantly lower risk than MTX. The results for
SCC are difficult to interpret due to wide confidence intervals.
The results require further validation in psoriasis populations
with larger numbers of exposed patients.
P063Interleukin-10 regulates skin thickness and scalingin imiquimod-induced psoriasis-like skininflammation in miceX. Xu,1 E. Prens,1 E. Florencia,1 L. Boon,2
P. Asmawidjaja,1 A.-M. Otten-Mus1 and E. Lubberts1
a. Crude incidence rates of NMSC after exposure to biologics or methotrexate
NMSC SCC BCC
Events IR (95% CI) Events IR (95% CI) Events IR (95% CI)
All study (19 261 PY) 72 0.37 (0.30–0.47) 24 0.12 (0.08–0.19) 48 0.25 (0.19–0.33)All biologics (18 480 PY) 61 0.33 (0.26–0.42) 23 0.12 (0.08–0.19) 38 0.21 (0.15–0.28)UST (7900 PY) 15 0.19 (0.11–0.31) 5 0.06 (0.03–0.15) 10 0.13 (0.07–0.24)TNFi (10 580 PY) 46 0.43 (0.33–0.58) 18 0.17 (0.11–0.27) 28 0.26 (0.18–0.38)Methotrexate (781 PY) 11 1.41 (0.78–2.54) 1 0.13 (0.02–0.91) 10 1.28 (0.69–2.38)
b. HRs of NMSC after exposure to biologics or methotrexate
All biologics 0.61 (0.28–1.35) 2.63 (0.31–22.6) 0.42 (0.17–1.01)P = 0.22 P = 0.38 P= 0.054
UST 0.35 (0.14–0.87) 1.37 (0.14–13.5) 0.26 (0.09–0.72)P= 0.023 P = 0.79 P= 0.0095
TNFi 0.81 (0.37–1.80) 3.49 (0.40–30.1) 0.55 (0.22–1.36)P = 0.61 P = 0.26 P = 0.19
IRs are events per 100 person-years.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
44 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
103ABSTRACTS
1Erasmus Medical Center, Rotterdam, the Netherlands and 2Bioceros, Utrecht,
the NetherlandsPsoriasis is an autoimmune skin disease affecting around 0.6–3%of the whole population, with detrimental physical and societal
impacts. Previously we established a psoriasis-like skin inflamma-
tion model in mice using topical application of imiquimod. This
model successfully recaptures most of the critical features of acute
psoriasis, such as keratinocyte hyperproliferation and Munro’s
microabscesses, and shares a similar infiltration profile of various
immune cells. Previous data suggested upregulation of interleukin
(IL)-10 during induction of the imiquimod model, but its role in
this psoriasiform model was not clear. Our aim was thus to inves-
tigate the role of IL-10 in imiquimod-induced psoriasis-like skin
inflammation. Psoriasis-like skin inflammation was induced by
topical application of imiquimod (Aldara) for 5 and 10 days.
Mice were injected intraperitoneally with anti-IL-10 or an isotype
control antibody, or subcutaneously with dexamethasone. The
back skin of mice was scored for up to 10 days using a modified
Psoriasis Area and Severity Index (PASI) score system adapted
from clinical PASI score. Inflammation and skin thickness were
scored histologically. Gene expression and immune cells in the
skin were analysed using quantitative polymerase chain reaction
and flow cytometry, respectively. At day 10, both the skin thick-
ness and scaling score were significantly higher after neutralizing
IL-10 compared with isotype control, and in both groups com-
pared with dexamethasone-treated animals. At days 5 and 10,
haematoxylin and eosin staining confirmed that epidermal thick-
ness was more prominent in anti-IL-10-treated mice than in iso-
type control or dexamethasone-treated mice, with more
profound differences at day 10. Ki-67 staining for proliferating
keratinocytes showed more proliferation at the epidermal basal
layer after neutralizing IL-10. In addition, significantly more infil-
tration of neutrophils was found in skin at day 10. In the early
phase (day 5), IL-23/IL-17 pathway cytokines were more signifi-
cantly upregulated in anti-IL-10 antibody-treated group than in
the isotype control group, while at a late stage (day10) a signifi-
cant upregulation was found in IL-19 and IL-24 expression. IL-10
regulates skin thickness and scaling during psoriasis-like skin
inflammation. Furthermore, our data suggest that IL-10 might
influence psoriatic symptoms through dampening of the IL-23/
IL-17 axis in the early phase and by reducing IL-19 and IL-24
expression at the late stage. This negative feedback signal of IL-10
partially explains the observed decrease of inflammation in imi-
quimod-induced skin inflammation after day 5.
P064The identification of interleukin (IL)-17A+, IL-17RA+
and IL-17RC+ lymphoid and myeloid cells in bloodof treatment-naive early patients and in synovialfluid of established patients with psoriatic arthritisX. Xu,1 N. Davelaar,1 A.-M. Otten-Mus,1
P. Asmawidjaja,1 H. den Braanker,1 J. Hazes,1
R. Bisoendial,1,2 M. Vis1 and E. Lubberts1
1Erasmus Medical Center, Rotterdam, the Netherlands and 2Maasstad
Hospital, Rotterdam, the Netherlands
Interleukin (IL)-17A is a proinflammatory cytokine involved
in the pathogenesis of psoriatic arthritis (PsA). Biologics tar-
geting IL-17A have been approved in clinical treatment of
patients with PsA. However, various cells can produce IL-17A,
and it is not clear which cell types are responsible for IL-17A
production in patients with PsA. Additionally, the expression
of IL-17A receptors, IL-17RA and IL-17RC, on different cell
types is not well defined. In this study, IL-17A-, IL-17RA- and
IL-17RC-positive cells in blood of patients with a first diagno-
sis of PsA with arthritis, and in synovial fluid of patients with
established PsA with active disease were examined. Fresh
blood was taken from first diagnosed disease-modifying anti-
rheumatic drug- and steroid-naive patients with PsA (n = 10)
with arthritis in at least one joint (PsA blood). Diagnoses were
made by rheumatologists according to the CASPAR criteria.
Fresh synovial fluid was obtained from patients with estab-
lished PsA (PsA SF) with active disease (n = 10) and treated
with either methotrexate (n = 3), adalimumab (n = 3) or
nonsteroidal anti-inflammatory drugs (n = 4). Multicolour
flow cytometric analysis was performed on PsA blood and PsA
SF. Different lymphoid and myeloid cell types were IL-17A-
positive in PsA blood of first-diagnosed patients with PsA,
such as CD3+, T-cell receptor (TCR)-cd+, CD4+ and CD8+
lymphoid cells; CD14+ monocytes; and CD15+ FcER1a+ eosi-
nophils. In PsA SF of patients with established PsA, T cells,
neutrophils, natural killer cells and eosinophils were IL-17A
positive. In both groups, no difference in expression of IL-
17RA and IL-17RC was found on CD4+, CD8+,
CD4+ CD45RO+ CCR6�, TCR-cd+ and CD19+ lymphoid cells
compared with the isotype control. In contrast, the expression
of IL-17RA and IL-17RC was increased compared with the iso-
type control on neutrophils and monocytes in PsA blood and
on neutrophils, monocytes, mast cells and eosinophils in PsA
SF. These preliminary data show that not only lymphoid cells
but also specific myeloid cell types may be sources of IL-17A
in PsA. Furthermore, not only lymphoid cells but IL-17RA/
IL-17RC-positive myeloid cells such as monocytes, neutrophils,
mast cells and eosinophils may be potential target cells for
IL-17A. Together, these data suggest a broader, but specific
IL-17A- IL-17RA/RC signalling network among different cell
types involved in the IL-17A-driven pathogenesis of PsA.
P065Distinct and overlapping activities of interleukin(IL)-17A and tumour necrosis factor (TNF) on theexpression of proinflammatory cytokines andmatrix metalloproteinases in psoriatic arthritis:rationale for anti-IL-17A/anti-TNF-a combinationtherapy?X. Xu,1 N. Davelaar,1 A.-M. Otten-Mus,1
P. Asmawidjaja,1 J. Hazes,1 D. Baeten,2 M. Vis,1
R. Bisoendial1,3 and E. Lubberts1
1Erasmus Medical Center, Rotterdam, the Netherlands; 2Academic Medical
Center, Amsterdam, the Netherlands and 3Maasstad Hospital, Rotterdam, the
Netherlands
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 45
Tumour necrosis factor (TNF) and interleukin (IL)-17A are
proinflammatory cytokines critically involved in the pathogen-
esis of psoriatic arthritis (PsA). Currently, targeting TNF is the
first choice of biological disease-modifying antirheumatic
drugs (bDMARDs) in PsA. However, up to 30% of patients
receiving anti-TNF monotherapy fail to respond and require
switching to a second TNF inhibitor or bDMARD with a dif-
ferent mode of action. Strategies targeted at neutralizing
IL-17A have been shown to have beneficial effects on skin,
enthesitis, dactylitis and joint inflammation. Here we explore
the effect of neutralizing IL-17A vs. anti-TNF on the expres-
sion of proinflammatory cytokines and metalloproteinases
(MMPs) and whether dual therapy targeting TNF and IL-17A
may have superior activity than treatment with either agent
alone. An allogeneic coculture system was used comprising
synovial-fluid T helper memory cells and synovial fibroblasts
(SFs) derived from patients with active PsA. Anti-CD3/CD28
stimulation was used during culture, and an anti-IL-17A anti-
body (secukinumab), anti-TNF-a antibody (adalimumab) or
their combination was added. PsA-unstimulated synovial T
helper memory cells cocultured with PsA SFs were included as
a control group, along with an isotype antibody control
group. After 72 h, supernatants were harvested for enzyme-
linked immunosorbent assay and cells were lysed for quantita-
tive polymerase chain reaction analysis. Anti-TNF antibody
treatment had no effect on IL-17A, levels and neutralization of
IL-17A did not influence the TNF production in the coculture
system. Both anti-TNF and anti-IL-17A single treatment signif-
icantly inhibited the production of IL-8 and reduced the
mRNA expression of IL-1b. Interestingly, neutralizing IL-17A
resulted in a significant suppression of IL-6 level, which was
not reduced by anti-TNF. Anti-TNF inhibited the production
of MMP-3, and only the combination of anti-TNF and anti-IL-
17A resulted in a significant suppression of MMP-1 levels and
MMP-9 mRNA expression. MMP-13 mRNA expression was
significantly suppressed by anti-TNF but not by anti-IL-17A;
however, neutralizing both IL-17A and TNF showed a
significant improvement in downregulating MMP-13 mRNA
expression compared with single cytokine treatment. More-
over, anti-IL-17A reduced RANK mRNA expression, which
was significantly more suppressed compared with anti-TNF
alone. However, no additive effect was noted for the combi-
nation blocking. Interestingly, only neutralizing both IL-17A
and TNF significantly reduced the mRNA expression of
RANKL. Osteoprotegerin (OPG) mRNA expression was not
influenced by anti-IL-17A and/or anti-TNF treatment. Neutral-
izing IL-17A or TNF in the PsA synovial T-cell–SF coculture
system resulted in overlapping but also distinct effects on
proinflammatory cytokine expression. TNF inhibition mark-
edly suppress different MMPs with mostly an additional effect
upon neutralization of IL-17A. Neutralization of both IL-17A
and TNF is needed to downregulate RANKL expression, which
changes the RANKL/OPG balance. Together, these preliminary
data suggest that dual therapy targeting IL-17A and TNF may
be superior in protecting against erosive arthropathy in PsA
than treatment with either agent alone.
P066Unopposed interleukin (IL)-36 activity promotesclonal CD4+ T-cell responses with IL-17A productionin generalized pustular psoriasisA. Arakawa, S. Vollmer, P. Besgen, B. Summer,P. Thomas, T. Ruzicka and J.C. PrinzLudwig-Maximilians-University, M€unich, GermanyMutations in IL36RN, CARD14 or AP1S3 provide genetic evi-
dence for autoinflammatory aetiology in generalized pustular
psoriasis (GPP). Although GPP has been considered as the
most severe psoriasis variant, the pathogenetic overlap with
psoriasis vulgaris (PV) remains elusive. As PV is a CD8+ T-cell
mediated autoimmune disease, we investigated the role of T
cells in GPP using PV as a disease control. Here we demon-
strate that unopposed Interleukin (IL)-36 signalling may coop-
erate with certain human leucocyte antigen (HLA) class II
alleles to induce antigen-driven T helper (Th)17 responses in
GPP, which are presumably directed against autoantigens in
the absence of exogenous triggers. We analysed eight patients
with GPP to show that deficits in IL36RN function may result
from IL36RN mutations or decreased IL36RN transcription.
Molecular analysis of T-cell receptor (TCR) rearrangements
revealed strong TCR-driven activation signatures in CD8+ T
cells of patients with PV and GPP and identical T-cell clones in
blood and skin lesions, suggesting common pathogenic path-
ways in PV and GPP. Notably, CD4+ T cells of patients with
GPP were characterized by strong autoproliferation, highly
restricted clonal TCR repertoires, identical T-cell clones in
blood and skin lesions, and predominant differentiation into
Th17 cells, whereas TCR-driven CD4+ T-cell activation was
modest in PV. The clonal CD4+ T-cell populations preferen-
tially produced IL-17A, a key mediator in GPP. IL36B substan-
tially enhanced TCR-mediated proliferation of CD4+ T cells
in vitro. Moreover, the patients with GPP showed high occur-
rence of certain HLA-class II alleles, HLA-DQB1*03, HLA-
DQB1*05 and HLA-DRB1*14, in contrast to weak HLA-class II
associations of PV. Thus, CD4+ T-cell involvement clearly dif-
ferentiated GPP from PV. GPP might therefore represent a dis-
ease where autoinflammation promotes CD4+ T-cell-mediated
autoimmunity in the context of HLA-class II-association.
P067Remarkable response of recalcitrant hyperkeratoticpalmoplantar psoriasis to itolizumab: a case reportU. Chakravadhanula1 and B.K. Jha2
1Vaikhan Hospital, Hyderabad, India and 2Medical Affairs, Biocon Ltd,
Bangalore, IndiaPalmoplantar psoriasis (PP) is a chronic inflammatory skin dis-
ease that is associated with distressful quality of life. The
prevalence of PP is 3–4% among all cases of psoriasis in most
studies. We present a case of PP that responded remarkably to
itolizumab. Itolizumab (Alzumab�) is a novel humanized
monoclonal antibody approved for moderate-to-severe chronic
plaque psoriasis. It downregulates T-cell proliferation induced
by activated leucocyte cell adhesion molecules by binding to
the extracellular scavenger receptor cysteine-rich distal domain
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
46 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
105ABSTRACTS
1 of CD6 (Krupashankar DS, Dogra S, Kura M et al. Efficacy
and safety of itolizumab, a novel anti-CD6 monoclonal
antibody, in patients with moderate to severe chronic plaque
psoriasis: results of a double-blind, randomized, placebo-
controlled, phase-III study. J Am Acad Dermatol 2014; 71:
484–92). A 42-year man presented at our clinic with PP with
both palms affected for over 3 years. The patient had already
received different treatment modalities including systemic and
biological therapy. His treatment history at another hospital
was as follows: high-potency topical corticosteroids and cal-
cipotriol; topical psoralen ultraviolet A therapy three times a
week for 6 months; and methotrexate 7.5 mg per week asso-
ciated with elevated transaminase values. Biological treatment
taken elsewhere was five doses of secukinumab, and inter-
leukin-17A inhibitor. The patient did not respond to the
aforementioned biological treatment. Also, this patient had a
history of thyrotomy. Due to failure of the aforementioned
treatment modalities, the patient, after screening for infection,
neoplasm and autoimmunity, which were negative, started on
itolizumab at a dose of 1.6 mg kg�1 (in 250 mL of normal
saline over 3 h) fortnightly followed by a maintenance phase
of three 4-weekly infusions. The patient achieved 85%
improvement in the Palmoplantar Psoriasis Area Severity Index
after the seventh infusion. His quality of life index also
improved significantly. Needless to say, only a small area of
the body is affected in PP or psoriasis of the palms and soles;
however, the symptoms lead to a distressful and disabling
quality of life, as this is a difficult-to-treat condition. In cases
where conventional therapies have failed, published studies
demonstrate that noncytokine biologics that act upstream (be-
fore T-cell activation), such as alefacept and efalizumab, have
been effective in treating PP (Lior S, Grigory K, Pnina S et al.
Therapeutic hotline. Alefacept in the treatment of hyperkera-
totic palmoplantar psoriasis. Dermatol Ther 2010; 23: 556–560).Similarly to the efficacy profile of other upstream-acting bio-
logics, namely alefacept and efalizumab, itolizumab also
resulted into a remarkable response to PP in the present stud-
ied case. It can be postulated that itolizumab immunomodu-
lates the downstream cytokine infiltration in PP without
inhibiting the constitutive expression of lymphocytes, thus
showing a better safety profile. Thus, itolizumab may be a safe
and efficacious treatment option in PP, a difficult-to-treat vari-
ant of psoriasis.
P068Effects of methotrexate on treatment and seruminflammatory cytokines in paediatric patients withsevere plaque psoriasisZ. Xu, Y. Gu and Z. WangDepartment of Dermatology, Beijing Children’s Hospital, Capital Medical
University, Beijing, ChinaAlthough the majority of cases of childhood psoriasis can be
managed with various topical agents, a proportion of patients
with severe disease need systemic therapies. Methotrexate
(MTX) is a well-known systemic treatment for severe paedi-
atric plaque psoriasis; however, evidence of its effectiveness
and safety is scarce, and its impact on serum inflammatory
cytokines remains unclear. This study aims to evaluate the
effectiveness of MTX in paediatric severe plaque psoriasis and
to describe changes in serum levels of interleukin (IL)-17A,
IL-23 and tumour necrosis factor (TNF)-a observed during
MTX treatment. The indication for MTX use is baseline Psoria-
sis Area and Severity Index (PASI) ≥ 15 or baseline body sur-
face area ≥ 20%. MTX was given at a single weekly oral dose
of 0.1–0.3 mg kg�1 to 18 paediatric patients with severe pla-
que psoriasis for 24 weeks. The efficacy of MTX was evaluated
by PASI and Children’s Dermatology Life Quality Index
(CDLQI). The levels of IL-17A, IL-23, TNF-a in peripheral
blood at baseline and week 24 were measured by liquid-phase
suspension chip. The PASI of the 18 patients significantly
decreased at weeks 4, 8, 12 and 24 compared with baseline
(30.4 � 8.9 vs. 21.9 � 12.1, t = 2.39; 30.4 � 8.9 vs. 12.9
� 9.6, t = 5.47; 30.4 � 8.9 vs. 4.7 � 3.4, t = 9.92; 30.4 �8.9 vs. 1.8 � 2.2, t = 8.93, all P < 0.05). PASI 75 (≥ 75%
improvement from baseline) was achieved in 12%, 40%, 77%
and 100% of patients at week 4s, 8, 12 and 24, respectively.
The median CDLQI decreased significantly at weeks 12 and
24. After 24 weeks of MTX treatment, the serum concentra-
tions of IL-17A, IL-23, TNF-a were lower than those at base-
line (Z = �2.42; Z = �2.31 and Z = �2.55, respectively, all
P < 0.05).The adverse events included nausea, loss of appetite,
and slightly elevated alanine aminotransferase and aspartate
transaminase. A low dose of MTX is effective and safe for sev-
ere paediatric plaque psoriasis. The serum levels of inflamma-
tory cytokines decline as PASI decreases.
P069Sustained remission in a patient with chronicplaque psoriasis treated with itolizumab: a 4-yearfollow-up experienceS.G. Parasramani,1 G.G. Kunder,2 S.H. Suresh2 andD.R. Pawar21Lilavati Hospital, Mumbai, India and 2Medical Affairs, Biocon, Bangalore,
IndiaA 53-year-old female patient with a history of psoriasis for
12 years was presented to us. On investigation it was found
that she had earlier been treated with topicals and methotrex-
ate. As her baseline Psoriasis Area and Severity Index (PASI)
on presenting to us was 21.8 and she had previously been
treated with the available treatment options she was suggested
to start biologics. The aim for use of biologics was to provide
the patient with quicker relief and long-term sustained
disease-free remission. The biologic of choice here was
itolizumab, a monoclonal anti-CD6 antibody that showed evi-
dence of remission in the phase III trial of the drug (Dogra S,
D SK, Budamakuntla L et al. Long-term efficacy and safety of
itolizumab in patients with moderate-to-severe chronic plaque
psoriasis: a double-blind, randomized-withdrawal, placebo-
controlled study. J Am Acad Dermatol 2015; 73: 331–3). Beforeinitiating the therapy, laboratory parameters of the patient
including serum creatinine, blood urea, liver function tests
and thyroid function tests, along with X-ray chest and
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 47
electrocardiogram, were analysed and normal. Tests for HIV,
hepatitis B and hepatitis C, and Mantoux test were negative.
After all the examinations were normal the patient was given
intravenous itolizumab 1.6 mg kg�1 body weight (75 mg in
250 mL of normal saline over 2 h). In total 10 injections
were given over a period of 6 months, followed by mainte-
nance dosing once every 3 months. The patient achieved PASI
90 response (90% improvement from baseline) at the end of
the 6th week (PASI score 1.9) and progressed to PASI 100
(PASI score 0.1) after the completion of 10 doses. In order to
maintain remission the patient is being given maintenance
dosing once every 3 months, and to date continues to main-
tain PASI 90 after 41 weeks of therapy (over 4 years). These
results are in agreement with the phase III studies of itolizu-
mab and have improved the clinical and quality-of-life
parameters of the patient. Thus itolizumab serves as the drug
of choice to maintain disease-free remission in moderate-to-
severe chronic plaque psoriasis.
P070Treat to target in psoriasis: a Belgian attempt todefine a tight control strategy for psoriasismanagementL. Grine,1 S. Segaert,2 J. Lambert,3 M. de laBrassinne,4 P.-D. Ghislain,5 F. Willaert,6 T. Hillary7 andJ. Lambert1
1Ghent University Hospital, Ghent, Belgium; 2University Hospital Leuven,
Leuven, Belgium; 3University Hospital of Antwerp, Antwerp, Belgium;4Centre Hospitalier Universitaire de Li�ege, Li�ege, Belgium; 5Clinical Research
Cliniques Saint-Luc, Brussels, Belgium; 6Erasme University Hospital, Brussels,
Belgium and 7Free University of Brussels, Brussels, BelgiumTreat to target (T2T) is defined as a therapeutic algorithm
designed around well-defined and specific therapeutic targets
in the management of a disease. This concept is characterized
by ‘tight control’, whereby a treatment algorithm is followed
regarding evaluation, assessment and treatment decision. T2T
strategies have gained a lot of interest since their first successes
in rheumatoid arthritis and diabetes. It seems the time has
come to introduce T2T in psoriasis, although many attempts
cannot be readily translated to the Belgian situation. We aim
to redefine a T2T strategy in light of the Belgian real-world
setting, which is currently ongoing. Questioning will be per-
formed through the Delphi technique, to build consensus
using a series of questionnaires to collect data from a panel of
experts. An expert board of Belgian key opinion leaders will
participate in defining a tight control strategy in Belgium. The
initial meetings are about the T2T concept, Belgian regula-
tions, relevant topics that need to be addressed, and introduc-
tion of the Delphi-structured questioning. The key opinion
leaders will be asked to expand the number of experts by pro-
viding names of relevant psoriasis experts to be included as
additional respondents. Next, the Delphi questionnaire will be
developed based on literature review and discussion points
during the meetings by two independent researchers. Answers
will be given on a 11-point Likert-scale; open questions may
be asked to explain the respondent’s rationale. The responses
will be categorized for the second iteration, which will enable
quantification of rationales. Responses will be analysed and a
second questionnaire will be created, including trends (me-
dian and interquartile) of the responses. For the second round,
the adapted questionnaires will be sent to the participants, and
they will be asked to modify or confirm their previous
answers or to specify the reasons for remaining outside the
consensus. Afterwards, a final analysis of the consensus will be
done. The primary outcome of this study will be to reach
consensus on a target specifically for psoriasis in Belgium, in
order to base algorithmic treatment decisions on this target.
Key secondary end points include a treatment algorithm (T2T
strategy) and a protocol for a randomized controlled trial to
evaluate the T2T strategy in Belgium. This study will provide
direct evidence on how Belgian psoriasis experts view the
tight control strategy for psoriasis in light of Belgian reim-
bursement, and whether T2T is feasible in Belgian clinical
practice for increased cost-effective use of current treatments.
P071Retrospective review of psoriasis ustekinumaboutcomes using real clinic data analysed usingstarting Psoriasis Area and Severity Index (PASI)and worst PASI in the preceding 5 years with PASI75 and 90 reportedC. Goodhead and P. HamptonRoyal Victoria Infirmary, Newcastle, U.K.The electronic notes of 114 patients who received ustek-
inumab for chronic plaque psoriasis were reviewed. Baseline
Psoriasis Area and Severity Index (PASI) were calculated using
different methods: (i) starting PASI (on day of first drug
administration) vs. (ii) worst PASI in the preceding 5 years.
Variations with weight and dose were also analysed. Patients
starting ustekinumab between December 2008 and January
2016 were included, and retrospective data were collected
Weight (kg)
Ustekinumab
dose Patients
PASI 90 at3 months using
starting PASI, %
PASI 75 at3 months using
starting PASI, %
PASI 75 at3 months using
worst 5-year PASI, %
PASI < 3 at 3 months
using starting PASI, %
≤ 80 45 mg 30 19 46 54 46
80.1–100 45 mg 28 18 39 57 4680.1–100 90 mg 18 35 65 71 59
100.1–120 90 mg 23 18 41 55 32> 120.1 90 mg 15 27 53 60 47
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
48 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
107ABSTRACTS
including weight, dose, baseline PASI, worst 5-year PASI and
PASI at 3, 6, 9 and 12 months. The starting PASI calculation
method used influenced PASI 75/90 rates at 3 months using
starting PASI: only 18% achieved PASI 90 vs. 26% using worst
5-year PASI. At 3 and 6 months all groups achieved higher
PASI 75/90 when the worst 5-year PASI was used vs. starting
PASI. The dose of ustekinumab used also influenced outcomes;
only 11% of patients receiving 45-mg doses achieved PASI 90
at 3 months vs. 24% receiving 90 mg. We noted a discrep-
ancy in outcomes using different measures; 18% of patients
reached PASI 90 at 3 months, but 45% achieved PASI ≤ 3.
Response differences were also seen between groups: group 3
(80.1–100 kg, 90-mg dose) achieved higher rates of PASI ≤ 3
at 3 and 6 months than the other groups (see Table) and had
greater achievement of PASI 75/90 at 3 and 6 months. A
dose-related difference in response was also seen with 90 mg,
with patients achieving higher PASI 90 rates at 3 months,
24% vs. 11% for 45 mg, and this difference appeared to les-
sen over time with 12-month PASI 90 rates being similar:
22% vs. 26%. In conclusion, variation in the starting PASI cal-
culation methodology can lead to differences in treatment out-
come reporting, and using absolute PASI in addition to PASI
75/90 can lead to greater transparency of reported results.
Although these data lack numbers for statistical significance
the findings may warrant further investigation from larger
datasets such as BADBIR.
P072Role of keratin 24 in human epidermalkeratinocytesM. Min,1 X.-B. Chen,1 P. Wang,1 L. Landeck,2
J.-Q. Chen,1 W. Li,1 S. Cai,1 M. Zheng1 and X.-Y. Man11Dermatology Department, Second Affiliated Hospital, School of Medicine,
Zhejiang University, Hangzhou, China and 2Ernst von Bergmann General
Hospital, Teaching Hospital of Charit�e, Humboldt University, Potsdam,
GermanyThe keratins are the typical intermediate filament proteins of
epithelia, showing an outstanding degree of molecular diver-
sity. As part of the epithelial cytoskeleton, keratins are impor-
tant for the mechanical stability and integrity of epithelial cells
and tissues. Moreover, recent studies have pointed to newly
recognized roles of certain keratins in apoptosis, cell growth,
tissue polarity, wound response and tissue remodelling. The
skin maintains its barrier function through tight regulation of
the proliferation and differentiation of keratinocytes, the pri-
mary cellular component of the epidermis. Previous studies
have shown that keratin abnormalities are associated with a
variety of skin diseases, including proliferative skin diseases
and hereditary skin diseases. In psoriasis, this differentiation
process is dysregulated, and keratinocytes exhibit hyperprolif-
eration and aberrant differentiation, which are two key hall-
marks of psoriatic lesions. Keratin 24 (K24) is a new kind of
keratin gene, which encodes a novel keratin protein. K24
bears high similarity to the type I keratins and displays a
unique expression profile. K24 is reported to be highly
expressed in keratinocytes, placenta, colon and spleen.
However, the function of K24 within the skin are still
unknown. The purpose of this study was to explore the
expression pattern and biological function of K24 in epidermal
keratinocytes, by which to lay the foundation for the study of
association between K24 and psoriasis. Skin biopsies were
taken from age-matched healthy volunteers and untreated
patients with psoriasis. Total RNA and protein were extracted
from the cultured primary epidermal keratinocytes. The mRNA
and protein levels of K24 were determined by quantitative
reverse-transcriptase polymerase chain reaction (qRT-PCR) and
Western blot, respectively. We further explored the expression
and location in the epidermis of skin specimens and normal
keratinocytes by immunofluorescence staining. To investigate
the role of K24 in keratinocyte differentiation, we character-
ized the expression of K24 on subcultured keratinocytes and
calcium-inducible differentiation. To determine the role of
K24 in keratinocytes further, K24 was overexpressed in pri-
mary keratinocytes by infection with lentivirus, which was
constructed with the K24 gene. The efficiency of overexpres-
sion of K24 in normal human epidermal keratinocytes was
confirmed by qRT-PCR and Western blot. Subsequently, the
effects of K24 overexpression on proliferation, differentiation,
apoptosis, cell cycle, senescence and migration were explored
by Western blot and functional analyses. In our study, the
protein level of K24 in normal keratinocytes was found to be
higher than that in psoriatic keratinocytes. Next we investi-
gated the localization of K24 within the epidermis and possi-
ble functions. K24 was found to be modestly overexpressed in
senescent keratinocytes and was mainly restricted to the upper
stratum spinosum of the epidermis. The protein was required
for terminal differentiation upon CaCl2-induced differentia-
tion. In vitro results showed that increased K24 in keratinocytes
dramatically changed the differentiation of primary ker-
atinocytes. It also inhibited cell survival by G1/S phase cell-
cycle arrest and induced senescence, autophagy and apoptosis
of keratinocytes. In addition, K24 activated the protein kinase
Cd signal pathway, involved in cellular survival. In summary,
K24 may be suggested as a potential differentiation marker
and antiproliferative factor in the epidermis.
P073Deletion of PCSK9 can suppress psoriasis-likeinflammation in an animal modelM. Chen,1 R. Yuan,2 C. Luan,1,2 X. Chen,2
J.M. Osland,2 S.J. Gerber,2 M. Dodds2 and Y. Hu11Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing,
China and 2Southern Illinois University School of Medicine, Springfield, IL,
U.S.A.Psoriasis is a systemic inflammatory disease associated with
metabolic disorders, including high levels of low-density
lipoprotein (LDL). Proprotein convertase subtilisin/kexin 9
(PCSK9), promoting the degradation of LDL receptors and
increasing the plasma LDL concentration, is also involved in
inflammation. This study aimed to examine the role of PCSK9
in psoriasis and to investigate the potential of topically apply-
ing small interfering (si)RNA targeting Pcsk9 as a new psoriasis
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 49
treatment. We investigated the imiquimod-induced psoriatic
reactions in Pcsk9 knockout and Pcsk9 siRNA-treated mice,
and also used cultured human keratinocytes to investigate the
role of PCSK9 on regulating cell proliferation and apoptosis.
We found that suppressing Pcsk9 can decrease the inflamma-
tory reaction induced by imiquimod treatment and inhibit
hyperproliferation of keratinocytes. The underlying mecha-
nisms may operate by suppressing the expression of nuclear
factor-jB and its downstream inflammatory cytokines, includ-
ing interleukin (IL)-17, IL-22 and IL-23. We also found that
suppressing PCSK9 can significantly suppress proliferation and
induce apoptosis of human keratinocytes. Taken together, our
findings indicate that PCSK9 plays an important role in psoria-
sis, and may be a novel therapeutic target.
P074Correlation between Dermatology Life QualityIndex and Psoriasis Area and Severity Index inpatients with psoriasis treated with ustekinumabJ.H. Hesselvig, A. Egeberg, N.D. Loft, C. Zachariae,K. Kofoed and L. SkovDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital,
University of Copenhagen, Hellerup, DenmarkBiological treatment is often reserved for patients with moder-
ate-to-severe psoriasis, where initiation and evaluation of the
effect is based on the clinical evaluation and on the patient’s
quality of life. In the initial phase of the treatment period a
strong correlation between Psoriasis Area and Severity Index
(PASI) and Dermatology Life Quality Index (DLQI) has been
shown. However, long-term correlation between PASI and
DLQI for patients treated with ustekinumab has not been
investigated in a real-life setting. In this register-based study
of patients with moderate-to-severe psoriasis, we investigated
the correlation between PASI and DLQI after 4 and
12 months. All patients with psoriasis treated with ustek-
inumab (n = 120) at our department from April 2009 to
March 2017 were included. A correlation analysis between the
change in PASI and DLQI and the individual questions in DLQI
were performed using Spearman’s rank correlation coefficient.
We observed a reduction in median PASI from baseline to
month 4 and a subsequent slight reduction until month 12,
with a similar pattern for DLQI. The correlation analysis
showed a moderate association between relative reduction in
PASI and DLQI with correlation values of 0.57 (P < 0.001)
for baseline to 4 months and 0.45 (P < 0.001) for baseline to
12 months. For the individual questions in DLQI the greatest
association was observed for questions on ‘symptoms and feel-
ings’. This was mainly attributed to improvement in the
symptoms (e.g. pain and pruritus) questions, with correlation
values close to those observed between PASI and overall DLQI:
0.52 (P < 0.001) for baseline to 4 months and 0.48
(P < 0.001) for baseline to12 months. The questions regard-
ing daily activities and treatment were only weakly associated
with improvements in psoriasis severity. The results suggest
objective improvements in severity of psoriasis to be weakly
to moderately associated with improvements in quality of life
in patients with psoriasis treated with ustekinumab. This study
was supported by an unrestricted grant from Janssen-Cilag.
P075Safety, efficacy and drug survival of biologics andbiosimilars for moderate-to-severe plaque psoriasisA. Egeberg,1 M.B. Ottosen,1 R. Gniadecki,2
S. Broesby-Olsen,3 T. Dam,4 L.E. Bryld,5
M.K. Rasmussen6 and L. Skov11Department of Dermatology and Allergy, Herlev and Gentofte Hospital,
Hellerup, Denmark; 2Department of Dermatology, Bispebjerg Hospital,
Copenhagen, Denmark; 3Department of Dermatology and Allergy Centre,
Odense University Hospital, Odense, Denmark; 4Skin Clinic, Nykøbing
Falster, Denmark; 5Department of Dermatology, Roskilde Hospital, Roskilde,
Denmark and 6Department of Dermatology, Aarhus University Hospital,
Aarhus, DenmarkReal-life data on newer biologics and biosimilar agents for
moderate-to-severe psoriasis are lacking. Our objective was to
examine the safety, efficacy and time to discontinuation (drug
survival) of biologics (adalimumab, etanercept, infliximab,
secukinumab and ustekinumab) and to compare the origina-
tors with biosimilars (i.e. Enbrel with Benepali, and Remicade
with Remsima). The DERMBIO registry contains data on all
Danish patients with moderate-to-severe plaque psoriasis trea-
ted with biologics. We examined patients treated between 1
January 2007 and 31 March 2017. We used Kaplan–Meier
survival curves and Cox regression to examine drug survival
patterns. There were a total of 3495 treatment series (2161
patients) including 1332 with adalimumab, 579 with etaner-
cept (621 when stratified by originator/biosimilar; 566 with
originator etanercept and 55 with biosimilar etanercept), 333
with infliximab (356 when stratified by originator/biosimilar;
266 with originator infliximab and 90 with biosimilar inflix-
imab), 1055 with ustekinumab and 196 with secukinumab.
Secukinumab had the highest number of responders with
100% improvement in Psoriasis Area and Severity Index (PASI
100) within the first 52 weeks, but also the lowest drug sur-
vival among all biologics. Ustekinumab had the highest drug
survival overall (ustekinumab > adalimumab > infliximab >etanercept > secukinumab). Long-term efficacy (PASI 75, 90
and 100, and absolute PASI ≤ 5, 3 and 1) was highest for
ustekinumab and adalimumab. There were no significant dif-
ferences in discontinuation risk between the originator and
biosimilar versions of infliximab or etanercept. During the first
24 weeks of therapy (including the induction dose), 3.5%,
39.0%, 22.7%, 0.0% and 20.0%, of patients were treated with
a higher dose of adalimumab, etanercept, infliximab, secuk-
inumab and ustekinumab, respectively, than the European
Medicines Agency (EMA) label dose. During maintenance
therapy (weeks 25–52), the EMA label dose was exceeded in
0.9%, 35.1%, 56.7%, 0.0% and 46.2% of patients, respec-
tively. When dose escalation was included in the models,
ustekinumab still had the highest drug survival of all biolog-
ics, followed by adalimumab. Adverse events (predominantly
infections) were most frequent for secukinumab and showed
an increased (albeit low) incidence of cardiovascular events
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
50 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
109ABSTRACTS
compared with the other agents. In conclusion, ustekinumab
was associated with the highest drug survival, and secuk-
inumab with the lowest. Switching from originator to biosim-
ilar had no significant impact on drug survival, and the safety
profiles were comparable. Adverse events occurred most fre-
quently with secukinumab. Future studies are warranted to
assess the long-term safety of novel biologics for psoriasis.
P076Predictive factors of pruritus among patients withpsoriasisC. Ebongo, S. Mansouri and B. HassamDermatology Department of Ibn Sina Hospital, Rabat, MoroccoPsoriasis is an inflammatory disease with cutaneous and articu-
lar tropism. It was previously considered not to be prurigi-
nous, but it is now well established that pruritus is a major
sign that can seriously alter the quality of life of these patients.
However, data regarding the prevalence of pruritus in psoria-
sis and its characteristics remain insufficient. The aim of our
study was to identify the predictive factors of pruritus in pso-
riasis. We conducted a retrospective cross-sectional study. All
patients with psoriasis who were hospitalized in our unit
between January 2007 and December 2016 were included. In
total 59 files were exploited. The average age was 42.8 years
and the sex ratio was 1.5: 1 men to women. Sixty-one percent
were married and 51% were unemployed. Regarding comor-
bidities we found one diabetic patient, eight with hyperten-
sion, six with obesity, three with dyslipidaemia, three
alcoholics, 10 who used tobacco and seven followed for
depression or anxiety. Psoriasis vulgaris was the predominant
form (71%), followed by erythroderma (15%), pustular
(10%) and the inverted form (3%). The mean cutaneous sur-
face area involved was estimated to be 43% and the mean Pso-
riasis Area and Severity Index score was 20.6. Pruritus was
found in 59% of patients and was severe in 37%. The analyti-
cal study found that the erythrodermic (P = 0.048) and pustu-
lar (0.038) forms, cutaneous surface area > 70% (P = 0.04)
and PASI > 15 (P = 0.01) were significantly associated with
the presence of pruritus. In contrast, obese patients were less
likely to have pruritus (P = 0.03). More and more publica-
tions are focusing on pruritus in psoriasis and its characteris-
tics. Aggravating factors have been reported such as stress,
cold and dry climates, skin xerosis, physical exercise and lack
of sleep. Pruritus also significantly alters the quality of life of
these patients while perpetuating the lesions by the Koebner
phenomenon. Indeed, the PASI score of patients with psoriasis
with pruritus is higher than that of patients without pruritus,
suggesting that pruritus should be considered as an additional
factor of severity in psoriasis. However, studies attempting to
compare the clinical characteristics of patients with psoriasis
and the presence of pruritus are rare. Management of patients
with psoriasis must integrate the management of pruritus
because it is a major sign responsible for the sustainability of
the lesions and also affects the quality of life of patients.
P077Education of patients with psoriasisC. Ebongo, S. Mai, M. Meziane and B. HassamDermatology Department of Ibn Sina Hospital, Rabat, MoroccoPsoriasis is a chronic inflammatory disease primarily affecting
the skin and joints. It is a multifactorial disease that affects
about 1–3% of the general population. Psychological repercus-
sions and impairment of life quality are important. The suc-
cess of the treatment requires the active participation of
patients. Therapeutic education of the patient aims to help
them acquire the skills necessary to manage their life with a
chronic illness. The aim of our study was therefore to assess
the impact of therapeutic education on patients with psoriasis.
We carried out a prospective 3-month study involving around
30 patients followed in our unit for psoriasis. The same ques-
tionnaire was used before and 1 month after the therapeutic
education in order to appreciate its contribution. The ques-
tionnaire included three main items with four to five ques-
tions each. In total 23 patients were included, 15 men and
eight women, with an average age of 27.8 � 3.2 years. Half
(51%) had a school level below high school and 75% earned
< €300 per month. Concerning questions related to the trans-
mission of the disease and its symptoms, before education
one-third of the patients had a score of correct answers
> 50% vs. four-fifths after education. In terms of associated
diseases and comorbidities, only one-sixth had a score > 50%,
vs. 100% after education. Regarding the treatment modalities
available and their follow-up, only three in 10 patients had a
score of correct answers > 50% before the education, vs. eight
in 10 after the education. There are diseases where therapeutic
education has been validated and is fully part of the manage-
ment of patients, such as diabetes, in which it has improved
metabolic control of the disease, improved quality of life and
reduced complications. Indeed, a better understanding of their
pathology seems to help patients to take an active part in their
care. In dermatology, therapeutic education has already proved
its worth in patients with atopic dermatitis. It would therefore
probably be beneficial to patients with psoriasis, especially that
considering that it has a chronic pathology with a strong psy-
chological impact. Therapeutic education remains an indis-
pensable tool in the management of patients with chronic
disease. However, the limitations of our study lie in the short
duration of study and our small sample. The establishment of
a specialized and multidisciplinary consultation for better care
should be considered.
P078Psychiatric comorbidity, psychotropic medicationprescribing and suicidality in patients withpsoriasis: a population-based cohort studyR. Parisi,1 R.T. Webb,2 C.E. Kleyn,3,4 M.J. Carr,2
N. Kapur,2 C.E.M. Griffiths3,4 and D.M. Ashcroft1,4,51Centre for Pharmacoepidemiology and Drug Safety, University of Manchester,
Manchester Academic Health Science Centre, Manchester, U.K.; 2Centre for
Mental Health and Safety, University of Manchester, Manchester Academic
Health Science Centre, Manchester, U.K.; 3Dermatology Centre, Salford Royal
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 51
NHS Foundation Trust, University of Manchester, Manchester Academic
Health Science Centre, Manchester, U.K.; 4NIHR Manchester Biomedical
Research Centre, Faculty of Biology, Medicine and Health, The University of
Manchester, Manchester Academic Health Science Centre, Manchester, U.K.
and 5NIHR Greater Manchester Patient Safety Translational Research Centre,
University of Manchester, Manchester Academic Health Science Centre,
Manchester, U.K.The psychological burden in people affected by psoriasis may
lead to elevated risks of suicide and nonfatal self-harm. This
study aimed to investigate psychiatric comorbidity, psy-
chotropic medication prescribing and suicidality in people
with psoriasis. Patients with a first diagnosis of psoriasis
between 1998 and 2014 were identified from the Clinical
Practice Research Datalink linked to Hospital Episode Statistics
and the Office for National Statistics mortality records in Eng-
land. For each patient with psoriasis, up to 20 comparison
patients were matched by age, sex, general practice and index
date. A stratified Cox proportional hazard model was used to
estimate the risk of suicide and nonfatal self-harm in people
with psoriasis. The multivariate model was adjusted for
socioeconomic status. Statistical models with interactions were
tested; these included an interaction between psoriasis and
age, sex or socioeconomic status. The cohort included 56 961
patients with psoriasis and 876 919 comparison patients. At
baseline, people with psoriasis had a higher prevalence of
depression (18.8% vs. 16.4%), anxiety (17.8% vs. 15.9%) and
bipolar disorder (0.64% vs. 0.51%) and were more often pre-
scribed psychotropic medications (54.5% vs. 49.1%). The
baseline prevalence of schizophrenia, eating disorder and per-
sonality disorder were similarly distributed in the psoriasis
and comparison cohorts (0.90% vs. 0.89%, 0.83% vs. 0.80%
and 0.56% vs. 0.55%, respectively). During a median follow-
up of 4.4 years (interquartile range 6.1), 35 and 679 suicide
events occurred in the psoriasis and comparison groups,
respectively, and, after exclusion of patients with a history of
self-harm, 592 and 6914 first self-harm events occurred in the
psoriasis and comparison cohorts, respectively. When taking
into account socioeconomic status, the risk of suicide was sig-
nificantly lower among patients with psoriasis [hazard ratio
(HR) 0.59, 95% confidence interval (CI) 0.41–0.85], and
there was no significant difference in risk of nonfatal self-
harm (HR 1.06, 95% CI 0.97–1.17). After testing for interac-
tions, the risk of suicide significantly differed according to age
(P = 0.02). The HR was 0.38 (95% CI 0.21–0.66) for patientsdiagnosed with psoriasis at ≥ 40 years, but there was no sig-
nificant difference in risk for those diagnosed at age
< 40 years. People with psoriasis have a greater prevalence of
depression and anxiety and are more likely to be prescribed
psychotropic medication than the general population. Never-
theless, having psoriasis is not associated with an elevated risk
of either suicide or nonfatal self-harm.
P079Dithranol in psoriasis: keratinocyte–neutrophilcross-talk as the early targetT.H. Benezeder,1 C. Painsi,2 G. Mayer,1
U. Schmidbauer,1 K. Hammer,2 B. Lange-Asschenfeld2 and P. Wolf1
1Department of Dermatology, Medical University of Graz, Graz, Austria and2Department of Dermatology, State Hospital Klagenfurt, Klagenfurt, AustriaDithranol is one of the most potent topical treatments for pso-
riasis, leading to fast Psoriasis Area and Severity Index (PASI)
reduction. Application of dithranol causes inflammation, but
its mechanisms of action have remained largely unclear until
now. The aim of this study was to investigate the therapeutic
mechanisms of dithranol treatment in plaque-type psoriasis.
Biopsy samples from 15 patients with psoriasis (mean baseline
PASI score 13.6 � 10.6) were taken before (day 0), during
(day 4 at maximum inflammation) and at the end of treat-
ment (week 2–3), and at the follow-up after dithranol therapy
(week 6–7). Dithranol treatment had reduced PASI in these
patients by a mean of 57% (range 42–74%) at week 2–3 and
by 59% (range 3–81%) in the follow-up. Gene expression in
the skin samples was evaluated by using Affymetrix Human
Gene 2.0 Arrays, and differentially expressed genes were iden-
tified based on fold changes (> 2.0) and t-tests (P < 0.05).
Gene expression analysis revealed significant upregulation with
a more normalized pattern of genes involved in establishment
of the skin barrier, epithelial homeostasis and keratinization in
lesional skin after 4 days of dithranol treatment compared
with baseline. Furthermore, antimicrobial peptides and
chemoattractants for neutrophils (e.g. CXCL8) were signifi-
cantly downregulated compared with lesional skin before
treatment. At the end of treatment the expression of these
genes decreased further and other genes involved in neu-
trophil-mediated inflammatory responses were also signifi-
cantly downregulated. With delay, proinflammatory cytokines
(interleukins IL-1b, IL-17, IL-22 and IL-36) significantly
decreased only at the end of treatment (week 2–3). Notably,genes involved in T-cell activation were not differentially
expressed during dithranol treatment. Consistently, a signifi-
cant decrease in dermal CD3, CD4, FoxP3 and CD8 cell counts
(as quantified by immunohistochemistry) was only seen at the
follow-up visit but not during dithranol treatment. Together
our results suggest that keratinocytes and their cross-talk with
neutrophils (and not cells of the acquired immune system)
are the primary targets of dithranol. (T.B. and C.P. equally
contributed to this work.)
P080Effectiveness and safety of off-label secukinumabdosing regimens for the treatment of moderate-to-severe plaque psoriasis in adult patients: aretrospective multicentre studyM. Phung,1 J.R. Georgakopoulos,2 A. Ighani3 andJ. Yeung4,51Department of Pharmacology and Toxicology, University of Toronto,
Toronto, ON, Canada; 2Schulich School of Medicine and Dentistry, Western
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
52 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
111ABSTRACTS
University, London, ON, Canada; 3Faculty of Medicine, University of
Toronto, Toronto, ON, Canada; 4Division of Dermatology, Faculty of
Medicine, University of Toronto, Toronto, ON, Canada and 5Probity Medical
Inc., Waterloo, ON, CanadaSecukinumab is a fully human IgG1k anti-interleukin (IL)-17A
monoclonal antibody used for the treatment of moderate-to-
severe plaque psoriasis in adult patients. It is widely accepted
that the proinflammatory cytokine IL-17A plays a central role
in the pathophysiology of this skin disease. Although secuk-
inumab 300 mg every 4 weeks has shown to be highly effec-
tive and safe, select patients in clinical practice display only a
partial response with this approved maintenance dosing regi-
men. Similarly, select patients achieve effective outcomes
immediately following the prescribed weekly loading doses;
however, they display minor disease relapse during the
interim period between injections. Clinicians may consider
using off-label dosing regimens to treat these patients due to
their unsatisfactory response to the approved regimen. Secuk-
inumab dose optimization involves shortening the dosing
interval of maintenance therapy. To our knowledge, no study
has evaluated the effectiveness and safety of these alternative
dosing regimens. Therefore, we aimed to evaluate off-label
secukinumab dosing regimens to inform real-world clinical
practice. We performed a multicentre, retrospective chart
review of patients aged ≥ 18 years treated with an off-label
secukinumab updosing regimen for moderate-to-severe plaque
psoriasis. Effectiveness [≥ 75% improvement in Psoriasis Area
and Severity Index (PASI 75) or Physician’s Global Assessment
(PGA) of 0 or 1] and safety (adverse events) were assessed at
baseline, prior to and after dose optimization. Of the six
patients who met inclusion criteria, four (67%) achieved and
two (33%) did not achieve PASI 75 or PGA 0/1 after
12 weeks of secukinumab treatment with the approved main-
tenance dosing regimen. These patients then elected to dose
optimize, where four (67%) patients had their dosing frequency
increased to 300 mg every 3 weeks, and two (33%) had theirs
increased to 300 mg every 2 weeks. After 12 weeks of treat-
ment with optimized dosing, all six (100%) patients achieved
PASI 75 from baseline or PGA 0/1. Overall, these patients expe-
rienced a significant clinical improvement after 12 weeks of
treatment with optimized dosing. No adverse events were
reported following dose optimization. These preliminary find-
ings suggest that increasing the dosing frequency of secuk-
inumab is safe and effective, benefitting patients with an
unsatisfactory clinical response to the approved dosing regimen.
In summary, dose optimization with secukinumab may be ben-
eficial in some patients with moderate-to-severe plaque psoriasis
and should be considered by clinicians in clinical practice.
P081Comorbidities in patients with psoriasis accordingto Charlson Comorbidity Index: 6 years ofexperience in Bogot�a, ColombiaC. Cortes, E. Pe~naranda, D. Chaparro, L. Pe~na andE. RoaHospital Universitario de la Samaritana, Bogot�a, Colombia
The survival of patients with psoriasis is modified by the
inflammatory component of this disease, especially when it is
associated with comorbidities. This which forces us to
improve promotion and prevention strategies in this group of
patients. Few studies have been carried out using a validated
comorbidity index that allows the practitioner to infer predic-
tive mortality information. The Charlson Comorbidity Index is
a score that includes 17 systemic diseases, used to predict the
5-year mortality of patients based on their different comor-
bidities. The University Hospital La Samaritana is a reference
centre for the state of Cundinamarca (Colombia), which has
socioeconomic conditions that differ from those of popula-
tions in which similar studies have been carried out. We do
not have studies in Colombia that allow us to know which are
the most frequent comorbidities in patients with psoriasis, or
the relationship of these comorbidities with the severity of
psoriasis. Our conclusions were as follows. The most prevalent
comorbidities in adult patients with psoriasis treated at the
University Hospital La Samaritana are dyslipidaemia (32%),
hypertension (26.1%) and obesity (23.8%). We did not find
a statistically significant association between the presence of
comorbidities and the clinical severity of psoriasis in this
group of patients. Cardiovascular and metabolic comorbidi-
ties are present in this group of patients regardless of clini-
cal severity. Charlson Comorbidity Index does not include
the most prevalent comorbidities in patients with psoriasis
(dyslipidaemia, hypertension and obesity), so we do not
consider it a good indicator of disease burden in this group
of patients. Studies that evaluate the association between
clinical severity of psoriasis and mortality are required.
Screening strategies should be implemented for all patients
diagnosed with psoriasis treated at the University Hospital
La Samaritana for the main comorbidities, regardless of
clinical severity.
P082Relationship between age of onset, male-to-femaleratio and family history of Japanese patients withpsoriasis: comparison with other East AsiancountriesB. Bayaraa and S. ImafukuFukuoka University, Fukuoka, JapanPsoriasis develops in patients of any age; however, the peak
age of onset differs among countries and ethnic groups. The
histogram of age of onset in Japanese patients with psoriasis is
bimodal, but the reason is yet unclear. To clarify the relation-
ship of age at onset, sex and family history of psoriasis in
Japanese patients with psoriasis, data from the Fukuoka
University Psoriasis Registry (FUPR) were analysed. Patients
who visited the Department of Dermatology, Fukuoka
University Hospital from 1998 to 2016 and were diagnosed
as having psoriasis were all registered at FUPR. Patients aged
0–79 years were extracted and analysed. To find out further
the characteristics of Japanese patients, the results were com-
pared with previously published similar data from other East
Asian countries. A total of 1089 patients were found in FUPR.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 53
The male-to-female ratio was 2.04 : 1. Two peaks of distribu-
tion in age of onset were seen, with the first peak in the 30s
for men and the 20s in women, and the second peak in the
50s for both sexes. Family history of psoriasis was seen in
6.4% in total; however, female patients had a much higher
rate (9.0%) compared with men (5.2%, P = 0.018). Further-
more, when stratified by age of onset, female patients with
onset < 30 years had a much higher rate (15.4%) than
women with onset > 30 years (5.6%, P = 0.0032). When
these data were compared with those from South Korea and
China, the onset age in both countries had a single peak,
which was located at a younger age than in Japan. Japanese
patents showed higher male predominance than those in
South Korea and China. South Korean and Chinese patients
had much more familial psoriasis (26% and 31%, respectively)
than Japanese. Age of onset of psoriasis in Japanese patients
was characteristically higher in both men and women than in
other Asian countries, with fewer cases of familial psoriasis.
Genetic background may affect these differences.
P083The journey of adult patients with psoriasistowards biologics past and present: results fromthe BioCAPTURE registryJ. van den Reek,1 M. Seyger,1 P. van L€uimig,1
R. Driessen,1 L. Schalkwijk,1 M. Berends,2 P. van deKerkhof1 and E. de Jong11Radboud University Medical Center, Department of Dermatology, Nijmegen,
the Netherlands and 2Slingeland Hospital, Doetinchem, the NetherlandsA considerable disease period, of 20 years on average, often
precedes initiation of a biological drug in patients with psoria-
sis. Little is known about this long but important period in
patients’ lives. An evaluation of this ‘journey’, and shifts
thereof in recent years, can reveal important insight and
opportunities for physicians, healthcare decision makers and
pharmaceutical manufacturers. We therefore aimed to describe
important patient and treatment characteristics until the start
of biological treatment in a cohort of patients with severe pso-
riasis. Moreover, we aimed to assess shifts of the ‘journey’ in
early (2005–2009) vs. established (2010–2015) biologics pre-scription periods. We performed an explorative, retrospective
study analysing the treatment characteristics of the period
from psoriasis diagnosis until first biologic. Data were col-
lected from the BioCAPTURE registry, presented with descrip-
tive statistics and visualized in bar charts. The journeys of
2005–2009 and 2010–2015 were compared with statistical
tests (e.g. v2-test and Mann–Whitney U-test) to identify
important shifts. Most patients received three different conven-
tional antipsoriatic systemic therapies before initiation of the
biologic. Methotrexate, ciclosporin and acitretin were most
frequently used. We noticed a small trend towards a shorter
‘journey’ with only two conventional systemic agents instead
of three before initiating a biologic in later years (2010–2015vs. 2005–2009). Ciclosporin, intensive topical treatment
(dithranol) and ultraviolet therapy have lost popularity in
recent years. The number of patients with hospital admissions
and day care admissions during the ‘journey’ significantly
decreased in patients starting a biologic in later years (2010–2015 vs. 2005–2009). We also noticed a significant decrease
in the rate of (day care) admissions in the 2 years before vs. the
2 first years during biological treatment. For instance, in the
period before starting a biologic, 17.7 admissions (day care
and hospital) per 100 follow-up years were seen vs. 8.6
admissions per 100 follow-up years in the first years of bio-
logical therapy (P < 0.001). To conclude, the journey of
patients with psoriasis towards a biologic is often extensive in
duration and in use of multiple conventional antipsoriatic
treatments. Discussion should continue on how to improve
this ‘journey’, as it could be a burdensome period with nega-
tive influence on patients’ lives and societal impact. The costs
of biologics, the safety profile of conventional systemic and
biologics, and the decrease in admissions during biologics
should be taken into account here. We think that especially
young and recently diagnosed patients could benefit from
optimization of their ‘journey’ towards biologics.
P084Skin mast cells: critical drivers of psoriasis?M.J. Barron, C.E.M. Griffiths and S. Bulfone-PausDivision of Musculoskeletal & Dermatological Sciences, School of Biological
Sciences, Faculty of Biology, Medicine and Health, University of Manchester,
Manchester, U.K.The aim of this study was to investigate the role of mast cells
(MCs) in the pathogenesis of psoriasis. We used immunohis-
tochemistry and metachromatic staining to evaluate MC distri-
bution and function in biopsies of psoriasis lesional (PP),
psoriasis nonlesional (PN) and healthy (NN) skin. Addition-
ally, we performed RNA sequencing analysis using cultured
MCs and those isolated from PP and PN skin. In PP skin there
was a twofold increase in MC density and a threefold increase
in the incidence of degranulation compared with PN and NN
skin. CD8� T cells in PP skin showed a 10-fold increased den-
sity, while macrophage density was increased fivefold. Finally,
nerve fibre and vascular density in PP skin were unchanged
and slightly raised, respectively, compared with PN and NN.
The relationship of MCs with CD8+ T lymphocytes and
macrophages showed strong spatial association in all skin
types analysed. However, in PP skin, MCs and nerve fibres
showed increased spatial association while MCs lost their
strong spatial association with the vasculature. In PP skin there
was a threefold increase in interleukin (IL)-17+ cells and a
parallel increase in IL-17+ MCs. We have isolated MCs from
PP and PN using flow cytometry and performed RNA sequenc-
ing analysis to delineate the gene expression of MCs in psoria-
sis. Our preliminary results show a dramatically increased
expression of genes involved in immune cell chemoattraction
in PP mast cells compared with those from PN, for example
CXCL1 (3.8), CXCL2 (2.3), CXCL3 (3.6), IL8 (2.8), CCL2 (1.8)
and CCL4 (3.0); the numbers in brackets are log2 fold
changes. This increased expression of chemoattractant genes
was also particularly pronounced in MCs from PP when
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
54 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
113ABSTRACTS
compared with quiescent MCs derived from peripheral blood,
including CXCL1 (5.1), CXCL2 (7.7), CXCL3 (4.8), IL8 (7.3),
CCL2 (2.9) and CCL4 (3.3); the numbers in brackets are log2fold changes. Our results show an increased prevalence of
MCs in PP skin in parallel with both CD8+ T cells and macro-
phages, two cell types that strongly associate with MCs. Fur-
thermore, the PP MCs population appears to traffic from the
vasculature to interact with dermal nerve fibres. Pruritus is a
common and distressing feature of psoriasis and the increased
proximity of MCs to nerve fibres in PP skin may be correlated
with this. The strong representation of proinflammatory,
chemoattractant genes and IL-17 expression in PP skin MCs is
consistent with this cell population being pivotal in driving
the inflammatory process in psoriasis.
P085Secukinumab demonstrates high sustained efficacyand a favourable safety profile through 5 years oftreatment in moderate-to-severe psoriasisR. Bissonnette,1 T. Luger,2 D. Thac�i,3 D. Toth,4,5
A. Lacombe,6 S. Xia,7 R. Mazur,6 P. Manmath,6
C. Pascal,6 M. Milutinovic6 and C. Leonardi81Innovaderm Research, Montreal, QC, Canada; 2University of M€unster,
M€unster, Germany; 3University Hospital Schleswig-Holstein, L€ubeck,
Germany; 4Probity Medical Research Windsor, Windsor, ON, Canada;5XLR8 Medical Research, Windsor, ON, Canada; 6Novartis Pharma AG,
Basel, Switzerland; 7Beijing Novartis Pharma Co. Ltd, Beijing, China and8Saint Louis University Health Science Center, St Louis, MO, U.S.A.Psoriasis is a chronic immune-mediated skin disease usually
requiring long-term management. Secukinumab, a fully
human monoclonal antibody that neutralizes interleukin (IL)-
17A, has been shown to have significant efficacy in the treat-
ment of moderate-to-severe psoriasis and psoriatic arthritis,
demonstrating sustained and long-lasting high levels of effi-
cacy with a favourable safety profile. This is the first phase III
study of an IL-17A inhibitor presenting long-term sustainabil-
ity and safety for up to 5 years of continuous treatment at the
approved dose. In the core SCULPTURE study, patients who
were Psoriasis Area and Severity Index (PASI) 75 responders
(≥ 75% improvement from baseline) at week 12 continued
receiving subcutaneous secukinumab 300 mg every 4 weeks
until year 1 (n = 168 at week 52). Patients subsequently
entered the extension phase and continued the same double-
blinded treatment regimen to year 3, and were thereafter
unblinded to year 5 (n = 126 at week 260), which was the
end of the study. Here we report final PASI 75/90/100, abso-
lute body surface area (BSA) ≤ 1/≤ 2/≤ 3, absolute
PASI ≤ 1/≤ 2/≤ 3 responses, Dermatology Life Quality Index
(DLQI) 0/1 response and safety and tolerability to year 5. Effi-
cacy data are reported as observed, and safety events are anal-
ysed per year. The mean baseline PASI and BSA were
23.5 � 8.8 and 33.1% � 18.9, respectively. PASI 75/90/100
responses at year 1 (88.9%, 68.5% and 43.8%, respectively)
were well sustained to year 5 (88.5%, 66.4% and 41%). The
average improvement in mean PASI was approximately 90%
compared with baseline through 5 years. Absolute PASI ≤ 1/
≤ 2/≤ 3 responses were sustained from year 1 (58.6%, 67.9%
and 74.1%, respectively) to year 5 (53.3%, 66.4% and
75.4%). Similarly, absolute BSA ≤ 1/≤ 2/≤ 3 responses at
year 1 (60.5%, 73.5% and 77.2%, respectively) sustained to
year 5 (62.3%, 71.3% and 78.7%). Two-thirds of patients
reported no impact of skin disease on their lives over 5 years
of treatment; DLQI 0/1 responses were 72.7% at year 1 and
65.5% at year 5. The safety profile of secukinumab remained
favourable, with no cumulative or unexpected safety concerns
identified. The most common adverse events included
nasopharyngitis, upper respiratory tract infection and head-
ache, consistent with those reported in the core study and pre-
vious phase III studies. The most frequent reasons for
discontinuation in the extension study were patient or guar-
dian decision (13, 7.7%), adverse event (10, 6%) and lack of
efficacy (seven, 4.2%). Secukinumab 300 mg treatment sus-
tained high levels of skin clearance, and improved quality of
life, through 5 years in patients with moderate-to-severe pso-
riasis. The favourable safety established in a large phase III
programme was maintained to 5 years. This investigation was
sponsored by Novartis Pharma AG, Basel, Switzerland.
P086Infliximab is associated with an increased risk ofserious infection in patients with psoriasis: resultsfrom the British Association of DermatologistsBiologic Interventions Register (BADBIR)Z. Yiu,1 C. Smith,2 D. Ashcroft,3 M. Lunt,4
S. Walton,5 R. Murphy,6 N. Reynolds,7,8
A. Ormerod,9 C.E.M Griffiths1 and R.B. Warren1
1Dermatology Centre, Salford Royal NHS Foundation Trust, The University
of Manchester, Manchester Academic Health Science Centre, NIHR
Manchester Biomedical Research Centre, Manchester, U.K.; 2St John’s
Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust,
London, U.K.; 3Centre for Pharmacoepidemiology and Drug Safety, School of
Health Sciences, The University of Manchester, Manchester, U.K.; 4Arthritis
Research U.K. Epidemiology Unit, The University of Manchester, Manchester,
U.K.; 5Department of Dermatology, Castle Hill Hospital, Hull, U.K.;6Sheffield University Teaching Hospitals and Sheffield Children’s Hospitals,
Sheffield, U.K.; 7Dermatological Sciences, Institute of Cellular Medicine,
Medical School, Newcastle University Newcastle upon Tyne, U.K.;8Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals
NHS Foundation Trust, Newcastle upon Tyne, U.K. and 9Division of Applied
Medicine, University of Aberdeen, Foresterhill, Aberdeen, U.K.There is concern that infliximab use for the management of
psoriasis may be associated with an increased risk of serious
infections. In the U.K., infliximab use for psoriasis is reserved
for patients with very severe disease [Psoriasis Area and Sever-
ity Index (PASI) ≥ 20; Dermatology Life Quality Index
(DLQI) > 18] compared with other biologics (PASI ≥ 10;
DLQI > 10). Thus, infliximab differs from other biologics in
that it is dosed intravenously and to a more severe population.
To account for this, we investigated the risk of serious infec-
tions associated with infliximab separately from the other bio-
logical therapies in patients with chronic plaque psoriasis
using a large prospective, U.K. and Republic of Ireland-based
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 55
pharmacovigilance registry (British Association of Dermatolo-
gists Biologic Interventions Register, BADBIR) reflecting real-
life clinical practice. The infliximab-treated cohort was com-
pared with a biologic-naive cohort who had received systemic
therapy, inclusive of exposure to methotrexate, ciclosporin,
acitretin, fumaric acid esters, psoralen–ultraviolet A or hydrox-
ycarbamide. Serious infections were those associated with hos-
pitalization, the use of intravenous antimicrobial therapy and/
or death. Propensity score inverse probability treatment-
weighted Cox proportional hazards models, adjusted for a pri-
ori identified potential confounders (including disease sever-
ity), were used to compare the risk of serious infection.
Missing data were accounted for using multiple imputations
of 20 cycles. All analyses were undertaken using Stata v14. In
total 3843 participants were included for analysis up to Octo-
ber 2016. The total and median follow-up time for infliximab
were 941.1 and 1.5 person-years [interquartile range (IQR)
2.5 person-years], and for the nonbiologic systemic cohort
6419.2 person-years and 1.5 (IQR 1.8) person-years. Forty-
five of 422 participants in the infliximab cohort experienced a
serious infection; 91 of 3421 participants experienced a seri-
ous infection in the nonbiologic systemic cohort. The inci-
dence rates were 47.8 per 1000 person-years [95% confidence
interval (CI) 35.7–64.0] in the infliximab cohort and 14.2 per
1000 person-years (95% CI 11.5–17.4) in the nonbiologic
systemic cohort. Infliximab was associated with a significantly
increased risk of serious infection overall (adjusted hazard
ratio 1.95, 95% CI 1.01–3.75). These data show that inflix-
imab use for psoriasis is associated with an increased risk of
serious infections compared with nonbiologic systemic thera-
pies. This risk should be taken into account when considering
infliximab for the management of patients with severe
psoriasis.
P087Efficacy and tolerance assessment of an anti-itching spray in patients with psoriasisS. Virassamynaik,1 B. Chadoutaud,2 C. Eydieux,2
J. Riviere2 and M. Sayag11Naos (Laboratoire Bioderma), Lyon, France and 2ClinReal Online, Toulouse,
FrancePsoriasis is a chronic and inflammatory skin disease where
patients usually experience pruritus. This symptom can have a
huge impact on their quality of life (e.g. sleep problems, dis-
comfort in daily activities). In order to sooth pruritus, an anti-
itching spray has been developed. It combines the Skin
ReliefTM technology and enoxolone, which have a specific
action on pruritus. To demonstrate its antipruritic efficacy and
the tolerance in patients with psoriasis, an observational,
prospective, multicentre study was carried in Poland. Thirty
patients with mild-to-moderate psoriasis were included by
three dermatologists. During 21 days, the spray was applied as
often as necessary on the area affected by pruritus. Efficacy
was evaluated by the 5D-pruritus scale and a clinical assess-
ment of the skin. Impact on the quality of life (Skindex) and
tolerance were assessed as secondary end points. After 21 days
of use, a significant decrease of the 5D-pruritus scale score
(�36%) and itching sensations (�48%) were observed. The
spray relieves pruritus in 20.2 s on average and the effect
lasted ≥ 2 h in 80% of patients. The cutaneous state was sig-
nificantly improved (dryness �41%, roughness �43%,
desquamation �43%, suppleness +25% and lesion extent
�29%). The product demonstrated a positive impact on qual-
ity of life by a significant decrease of Skindex score (�37%).
The spray was well tolerated by 100% of the patients. In con-
clusion, this study demonstrated that the spray quickly calms
the itching associated with psoriasis and provided patients
with sustainable relief. The spray not only improved symp-
toms, but was shown to enhance self-image and the social life
of patients.
P088Gene expression and protein changes from bloodand skin correlate with disease improvement inpatients with psoriasis treated with PF06700841,a tyrosine kinase2/Janus kinase 1 inhibitorL. Xi,1 E. Kieras,1 M. Suarez-Farinas,2 B. Zhang,1
K. Page,1 J. Lee,1 S. Du,3 L. Fitz,1 W. Gordon,3
W. Zhang,4 J. Krueger5 and E. Peeva31Pfizer Clinical Research, Cambridge, MA, U.S.A.; 2Icahn School of Medicine
at Mount Sinai, New York, NY, U.S.A.; 3Pfizer Inflammation &
Immunology Research, Cambridge, MA, U.S.A.; 4Pfizer Global Product
Development, Cambridge, MA, U.S.A. and 5The Rockefeller University, New
York, NY, U.S.A.A biomarker analysis from a phase I clinical study was con-
ducted to identify treatment response biomarkers of gene and
protein changes in blood and skin, and disease improvement
in patients with psoriasis treated with a tyrosine kinase 2/
Janus kinase 1 inhibitor. Skin biopsies and blood samples were
collected at weeks 0, 2 and 4 from patients enrolled in a study
designed to test the safety and efficacy of PF06700841, taken
once daily at 30 mg (n = 14) or 100 mg (n = 7), compared
with placebo (n = 9) for 4 weeks. Gene expression was quan-
tified from skin biopsies using the Affymetrix Human Genome
U133 Plus 2.0 Array and from Paxgene blood samples using
next-generation sequencing-based RNA sequencing on the
Illumina platform. Proteins (n = 303) were quantified in
serum using the Olink Proseek Multiplex Inflammation and
Cardiovascular (II & III) and Immuno-Oncology panels. A lin-
ear mixed model was used to evaluate the relationship
between change from baseline in biomarker measurements
and Psoriasis Area and Severity Index score, and to identify
biomarkers that respond to treatment. Genes downstream of
interferon-c (PLK3, CBX7 and IFIH1) and interleukin (IL)-17
(PDZK1IP1, PI3, LCN2, S100A8 and S100A9) correlated with dis-
ease improvement (P < 0.05) and were significantly modu-
lated in treated patients in skin or blood. Thirteen genes
correlated with disease improvement in both blood
(P < 0.05) and in skin (false discovery rate < 0.05). Two
genes showed interesting relationships between gene expres-
sion and protein and in tissue vs. blood. A mature dendritic
cell marker, LAMP3, showed decreased gene expression in skin,
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
56 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
115ABSTRACTS
as well as decreased protein in serum (P < 0.05); the gene
signal was not detected in blood. Another dendritic cell mar-
ker previously shown to colocalize with lymphocytes in psori-
asis lesions, CD83, was also downregulated in skin, as was the
protein in serum (30-mg treatment, false discovery rate
< 0.1), while there was an increase in gene expression in
blood. Treatment also induced downregulation of genes asso-
ciated with IL-4 signalling in skin, whereas increased expres-
sion of these genes was observed in blood. This approach to
compare gene expression and proteins in blood and skin iden-
tified a set of biomarkers associated with disease improvement
or treatment response. Several blood-based biomarkers were
identified that correspond to changes in skin. The differences
and parallels in biomarker modulation in blood and skin pro-
vide insights into the biological mechanisms of PF06700841
inhibition in psoriasis. Further investigation of these biomark-
ers in a larger cohort is warranted. This work was funded by
Pfizer.
P089Interleukin (IL)-36c induces IL-23 production andangiogenesis in psoriasisC. Bridgewood,1 G. Fearnley,2 A. Keszegpal,2
P. Laws,3 S. Ponnambalam,2 A. Graham,1 M. Stacey2
and M. Wittmann21University of Bradford, Bradford, U.K.; 2University of Leeds, Leeds, U.K.
and 3Chapel Allerton Hospital, Leeds, U.K.The interleukin (IL)-1 family member cytokine IL-36c is rec-
ognized as a crucial mediator in the immunopathology of pso-
riasis, hallmarks of which include the activation of both
resident and infiltrating inflammatory myeloid cells, and aber-
rant angiogenesis. This research demonstrates a role for IL-36cin both myeloid activation and angiogenesis. We show that
IL-36c induces the production of psoriasis-associated cytokines
from macrophages (IL-23, tumour necrosis factor-a) and that
this response is enhanced in macrophages from patients with
psoriasis. This effect is specific for IL-36c and could not be
mimicked by other IL-1 family cytokines such as IL-1a.IL-36c was also demonstrated to induce endothelial tube for-
mation and branching, in a vascular endothelial growth
factor-A-dependent manner. Furthermore, IL-36c-stimulated
macrophages potently activated endothelial cells as illustrated
by ICAM-1(CD54) upregulation, and led to increased adher-
ence of monocytes, effects that were markedly more pro-
nounced for psoriatic macrophages. Interestingly, regardless of
stimulus, psoriasis monocytes showed increased adherence to
both the stimulated and unstimulated endothelium when com-
pared with monocytes from healthy individuals. Collectively,
these findings add to the growing evidence for IL-36c having
roles in psoriatic responses, by enhancing endothelium-direc-
ted leucocyte infiltration into the skin and strengthening the
IL-23/IL-17 pathway. Our findings also point to a cellular
response that could potentially support cardiovascular
comorbidities in psoriasis in the form of increased monocyte
adherence.
P090One-year pilot study to evaluate sequential therapywith ciclosporin and itolizumab in treatment ofchronic plaque psoriasisU. Chakravadhanula,1 B.S. Chandrashekar,2
M. Parekh,3 D.S. Krupashankar,4 H.S. Swaroop5 andD. Pawar5
1SK Health Care foundation, Hyderabad, India; 2Cutis Academy of Cutaneous
Sciences, Bangalore, India; 3Jain Hospital, Bangalore, India; 4Malligae
Hospital, Bangalore, India and 5Medical Affairs, Biocon, Bangalore, IndiaItolizumab, an anti-CD6 monoclonal antibody, acts upstream
and inhibits the formation of cytokines. However, activation
of a positive feedback loop in keratinocytes leads to a delay its
onset of action. Hence this study has been conducted to target
the positive feedback loop initiated by interleukin-17 using
ciclosporin, and to target the upstream mediator CD6 by itoli-
zumab. This combined targeting could lead to faster control
and longer remission of psoriasis. Thus our objective was to
assess the efficacy of itolizumab as a sequential therapy with
ciclosporin in the treatment of patients with moderate-to-
severe plaque psoriasis. Adult patients with psoriasis with Pso-
riasis Area and Severity Index (PASI) > 10 were administered
oral ciclosporin 3–5 mg kg�1 bodyweight for the first
15 days. After a 24-h drug-free period, itolizumab 1.6 mg
kg�1 was administered intravenously every 15 days for the
first 3 months and thereafter monthly for the next 3 months.
Change in PASI score was evaluated every month until
52 weeks from the initiation of itolizumab. Twelve patients
with moderate-to-severe psoriasis with a mean baseline PASI
of 24.4 (range 10–47.5) were recruited. They achieved a
mean PASI score of 18.9 (range 5–36.5) after 14 days of
ciclosporin. After 12 weeks of itolizumab therapy seven
(58%) patients achieved PASI 75 (≥ 75% improvement from
baseline), with mean PASI score of 5.0 (range 2.6–7), and
two (16%) achieved PASI 90 with a mean PASI score of 1.1
(range 0.6–1.6). After 24 weeks of itolizumab therapy four
(33%) patients achieved PASI 75 with a mean PASI score of
4.6 (range 3.6–6.6) and six (50%) patients achieved PASI 90
with a mean PASI score of 1.6 (range 0.4–4.6). Two patients
failed to achieve PASI 75 after 24 weeks and withdrew from
the study. Nine (75%) patients maintained PASI 75 response
at the end of 52 weeks of itolizumab therapy. Two patients
had developed infusion reactions with mild severity during
the course of the therapy. The main limitation of the study is
the absence of a control group. In conclusion, sequential
blocking of both upstream and downstream mediators by
ciclosporin and itolizumab offers encouraging efficacy with
long-term remission. However, this needs to validated with
randomized controlled studies.
P091Examining the impact of treatment by adermatologist vs. nondermatologist in psoriasiscareM. Porter,1 N. Golbari,1,2 S. Lockwood1 andA. Kimball1
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 57
1Beth Israel Deaconess Medical Center, Boston, MA, U.S.A. and 2Stony
Brook School of Medicine, Stony Brook, NY, U.S.A.Despite recent treatment advances in the care of patients with
psoriasis, almost half of patients remain untreated or under-
treated (Armstrong AW, Robertson AD, Wu J et al. Undertreat-
ment, treatment trends, and treatment dissatisfaction among
patients with psoriasis and psoriatic arthritis in the United
States: findings from the National Psoriasis Foundation sur-
veys, 2003–2011. JAMA Dermatol 2013; 149: 1180–5). We
sought to identify patient-reported differences in disease man-
agement practices and treatment satisfaction when patients
were treated by dermatologists vs. nondermatologists (primary
care providers or rheumatologists). A 36-question survey was
administered to patients with psoriasis at Massachusetts Gen-
eral Hospital (MGH) and a local National Psoriasis Foundation
conference. All responses to the survey, including assessment
of disease severity, were self-reported. Only patients at MGH
had a verified diagnosis of psoriasis. Preliminary data included
responses from 60 patients. Treatment was prescribed by a
dermatologist for 52 patients vs. by a nondermatologist for
eight. Overall 73% of patients with psoriasis treated by a der-
matologist were also first diagnosed by a dermatologist, and,
similarly, 64% treated by a nondermatologist were first diag-
nosed by a nondermatologist. When comparing patients trea-
ted by dermatologists vs. nondermatologists, those treated by
dermatologists reported having psoriasis longer (20.2 vs.
11.6 years, P = 0.06), having greater disease improvement
(50% vs. 13%, P = 0.047), having greater satisfaction with
treatment (80% vs. 50%, P = 0.06) and feeling more
informed (89% vs. 57%, P = 0.03). Only 27% of dermatolo-
gist-treated patients reported mild disease, compared with
75% of nondermatologist-treated patients. Twelve patients
reported being treated with biological agents, and all were
prescribed by dermatologists. Our study found that patients
treated by dermatologists reported greater improvements in
their disease despite having more severe disease. Only derma-
tologists prescribed biological agents to those surveyed, and
this trend was also found in a previous survey of primary care
providers where none reported prescribing systemic therapy
(Lockwood S, Porter M, Kimball A. Addressing the under-
treatment of patients with psoriasis, preliminary survey results.
In: Society for Investigative Dermatology Annual Conference. Portland,
Oregon, 2017). Improving access to dermatology or education
and training for nondermatologists about psoriasis therapy
may benefit untreated or undertreated patients with psoriasis,
particularly those with severe or refractory disease. Further
studies to design targeted interventions for nondermatologists
or the referral process should be performed. Fellowship fund-
ing for two of the authors was provided through the National
Psoriasis Foundation.
P092Ixekizumab maintains reductions in Psoriasis Areaand Severity Index through the third year oftreatment: results from the UNCOVER-3 extensionstudyP. Fern�andez-Pe~nas,1 O. Goldblum,2 L. Berggren,2
N. Burkhardt2 and L. Puig31Depatment of Dermatology, Westmead Hospital, Westmead, Australia;2Eli Lilly and Company, Indianapolis, IN, U.S.A., and 3Dermatology Service,
Hospital de la Santa Creu i Sant Pau, Barcelona, SpainFor long-term assessment of efficacy, the achievement of a
low absolute Psoriasis Area and Severity Index (PASI) may be
more relevant than relative improvement from baseline PASI.
Here we report 3-year (156-week) PASI data of patients trea-
ted with ixekizumab, a high-affinity anti-interleukin (IL)-17A
monoclonal antibody. Patients received ixekizumab according
to the recommended dose (starting dose 160 mg, then 80 mg
every 2 weeks up to and including week 12, followed by
80 mg every 4 weeks) in the UNCOVER-3 study
(NCT01646177). Only visits treated at the recommended
ixekizumab dose were considered. Data collected after the first
visit with uptitrated 2-weekly long-term dosing were excluded
before imputations were applied. Data were summarized using
two methods. Firstly, multiple imputation (MI): partial impu-
tation of nonmonotone missing data (for intermittent missing
data) using a Markov chain Monte Carlo method with the
simple imputation model, then for the monotone missing
data, a sequential regression multiple imputation with the
baseline score. Secondly, mNRI (modified nonresponder
imputation): patients who discontinued due to adverse events
or lack of efficacy/relapse were considered nonresponders and
were imputed as nonresponders. In all other cases of missing
data for this analysis, the data were imputed using the above
MI method. At week 156, 249 of 385 patients (64.7%) had a
nonmissing PASI score with the recommended dose, and 136
of 385 patients (35.3%) had a missing value and were
imputed. The relative PASI responses were (MI/mNRI) PASI
75, 91.1%/83.9%; PASI 90, 76.9%/72.2%; PASI 100, 53.9%/
51.6%. At 156 weeks, the absolute PASI values were (MI/
mNRI) PASI ≤ 5, 91.5%/84.2%; PASI ≤ 3, 83.6%/78.0%;
PASI ≤ 2, 79.1%/74.5%; PASI ≤ 1, 70.0%/66.5%. No new
safety signals were seen for ixekizumab. In conclusion, ixek-
izumab showed sustained efficacy through 3 years of treat-
ment in clearing psoriasis, while maintaining a favourable
safety profile. This study was funded by Eli Lilly and Com-
pany, Indianapolis, IN, U.S.A.
P093Starting biologic treatment sequences for plaquepsoriasis with ustekinumab or adalimumab is themost cost-effective: a cost–utility analysis basedon 10 years of Dutch real-world evidence fromBioCAPTURES. Klijn,1 J. van den Reek,2 G. van de Wetering,1
A. van der Kolk,3 E. de Jong2 and W. Kievit4
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
58 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
117ABSTRACTS
1Pharmerit International, Health Economics and Outcomes Research,
Rotterdam, the Netherlands; 2Department of Dermatology and 4Radboud
Institute for Health Science, Radboud UMC, Nijmegen, the Netherlands and3Janssen-Cilag BV, Breda, the NetherlandsTreatment with biologics, such as etanercept, adalimumab or
ustekinumab, may be indicated for patients with moderate-to-
severe plaque psoriasis. Switching of biologics is common, but
it is unclear which biologic is most effective to initiate a
sequence of biologics. Comparative evidence on (cost)-effec-
tiveness of different biologics is limited. Given that biologics are
associated with high treatment costs, appropriate use of these
drugs is necessary. We aimed to evaluate the cost-effectiveness
of different biological treatment sequences for psoriasis based
on real-world evidence. A sequence model was developed to
evaluate the costs and health effects of different consecutive
lines of biological treatments based on the three most com-
monly prescribed biologics: adalimumab, etanercept and ustek-
inumab (for example adalimumab-etanercept-ustekinumab vs.
etanercept-ustekinumab-adalimumab) over a 10-year time hori-
zon. The model was populated with data from the Dutch Bio-
CAPTURE registry and scientific literature. The model estimated
10-year treatment costs and the total quality-adjusted life years
(QALYs) for each possible treatment sequence. Uncertainty was
addressed by both probabilistic and scenario analyses. We esti-
mated that sequences starting with etanercept would be the
most expensive, with 10-year costs from €147 499 to
€ 148 442; it was also the least effective with an average cumu-
lative health effect of 7.79 QALYs. A sequence starting with
ustekinumab followed by adalimumab would be the least
expensive, with 10-year costs of €141 962, while the cumula-
tive health effect is estimated to be 8.02 QALYs. A sequence
starting with adalimumab followed by ustekinumab was mar-
ginally more effective with 8.03 QALYs, but was also slightly
more expensive, with 10-year costs of €143 661. When inter-
preting these results, it should be taken into account that the
credible intervals were partly overlapping. We conclude from
these findings that the order in which biologics are used influ-
ences the cost-effectiveness of treatment in terms of both costs
and health effects. Initiation of a biological treatment sequence
for psoriasis may best be done with adalimumab or ustek-
inumab; etanercept seems less optimal from a health-economic
perspective. As the sequence order of biologics influences both
costs and health effects of psoriasis treatment, adopting a long-
term perspective at the start of treatment is important.
P09452-Week results from IXORA-S: a randomizedhead-to-head trial of ixekizumab and ustekinumabin patients with moderate-to-severe plaquepsoriasisC. Paul,1 P. van de Kerkhof,2 Y. Dutronc,3
C. Henneges,3 M. Dossenbach,3 K. Hollister3 andK. Reich4,5
1Dermatology, CHU, Paul Sabatier University, Toulouse, France; 2Department
of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, the
Netherlands; 3Eli Lilly and Company, Indianapolis, IN, U.S.A.,
4Dermatologikum Hamburg, Hamburg, Germany and 5SCIderm Research
Institute, Hamburg, GermanyIxekizumab is a high-affinity monoclonal antibody that selec-
tively targets interleukin-17A. It has demonstrated superior effi-
cacy to ustekinumab through Week 24 in IXORA-S
(NCT02561806) (Reich K, Pinter A, Lacour JP et al. Comparison
of ixekizumab with ustekinumab in moderate-to-severe psoria-
sis: 24-week results from IXORA-S, a phase III study. Br J Dermatol
2017; in press; https://doi.org/10.1111/bjd.15666). Here we
present the 1-year comparative efficacy and safety data. Patients
were randomized (1 : 1) to ixekizumab (n = 136) or ustek-
inumab (n = 166), dosed per their approved labels. Categorical
data were analysed using logistic regression including terms for
treatment, weight and geographical region. Nonresponder
imputation was used to account for missing data. The incidence
of adverse events (AE) between groups was compared using
Fisher’s exact test. This study was funded by Eli Lilly and Com-
pany, U.S.A. At week 52, the majority of efficacy response rates
were significantly higher for ixekizumab than for ustekinumab.
Treatment-emergent AEs (TEAEs), serious AEs and infection
rates were comparable between the two treatment groups; no
deaths occurred. Nasopharyngitis was the most common TEAE
and infection type. Significantly more injection-site reactions
occurred in the ixekizumab group. The results from IXORA-S
demonstrate the continued superior efficacy of ixekizumab over
ustekinumab at week 52. The safety profiles of both treatment
groups were in line with published reports [Reich et al.; Papp
KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustek-
inumab, a human interleukin-12/23 monoclonal antibody, in
patients with psoriasis: 52-week results from a randomised,
double-blind, placebo-controlled trial (PHOENIX 2). Lancet
2008; 371: 1675–84].
Ustekinumab,n = 166
Ixekizumab,n = 136 P-value
Response, n (%)
PASI 75 126 (75.9) 120 (88.2) 0.006PASI 90 98 (59.0) 104 (76.5) 0.003
PASI 100 59 (35.5) 71 (52.2) 0.014sPGA (0–1) 108 (65.1) 110 (82.1) 0.002
DLQI (0–1) 94 (56.6) 97 (71.3) 0.014Itch NRS ≥ 4-point
improvement
101 (74.3) 88 (80.0) 0.24
Safety, n (%)
TEAE 139 (83.7) 117 (86.7) 0.52Nasopharyngitis 63 (38.0) 45 (33.3) –Headache 21 (12.7) 15 (11.1) –Arthralgia 14 (8.4) 11 (8.1) –Serious AE 6 (3.6) 9 (6.7) 0.29Infections/infestations 107 (64.5) 83 (61.5) 0.63
Nasopharyngitis 63 (38.0) 45 (33.3) –Influenza 6 (3.6) 8 (5.9) –Bronchitis 9 (5.4) 3 (2.2) –Injection-site reactions 2 (1.2) 22 (16.3) < 0.001
DLQI, Dermatology Life Quality Index; NRS, Numerical Rating
Scale; PASI, Psoriasis Area and Severity Index; sPGA, Static Physi-
cian Global Assessment.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 59
P095The genotype of susceptibility genes in psoriasispredicting the response and hepatotoxicity tomethotrexate treatmentJ. Xu,1 X. Zhang1,2 and K. Yan11Huashan Hospital, Shanghai, China and 2Anhui Medical University, Anhui,
ChinaMethotrexate is an efficacious and cost-effective treatment as a
first-line agent for moderate-to-severe psoriasis. However, it is
limited in its use by unpredictable efficacy and toxicity. This
study was designed to test the hypothesis that susceptibility
genetic variations are associated with the efficacy and hepato-
toxicity of methotrexate. DNA was collected from 90 patients
with psoriasis who had been treated with methotrexate in a
prospective cohort. Phenotypic data on efficacy and hepatotox-
icity were available. Eighteen single-nucleotide polymorphisms
in 15 susceptibility genes were selected from our previous
reported susceptibility loci of psoriasis. The AG genotype in
CLE3D (rs4112788) and the TT genotype in TNIP1
(rs10036748) are associated with good response to
methotrexate therapy in patients with psoriasis; the latter gene
was also associated with hepatotoxicity. The TT genotype in
TNIP1 (rs10036748) and the AA genotype in ERAP1 (rs27043)
are related to the development of arthritis in patients with
psoriasis. These data indicate that the genotype of susceptibil-
ity genes may predict the efficacy and hepatotoxicity of
methotrexate treatment in psoriasis.
P096Evaluation of the efficacy of granulocyte andmonocyte adsorption apheresis on skinmanifestation and joint symptoms of patients withpustulotic arthro-osteitisH. Kawakami,1,2 N. Abe,1 Y. Matsumoto,1 H. Hirano,1
R. Tsuboi1 and Y. Okubo1
1Tokyo Medical University, Tokyo, Japan and 2Ageo Central General
Hospital, Saitama, JapanPustulotic arthro-osteitis (PAO), occasionally complicated with
palmoplantar pustulosis (PPP), affects patients’ activities of
daily living. Granulocyte and monocyte adsorption apheresis
(GMA) selectively removes activated granulocytes and mono-
cytes by means of extracorporeal circulation. Although the
efficacy of GMA in the treatment of generalized pustular psori-
asis has been proven, very few reports have assessed its effi-
cacy in the treatment of PPP and PAO. We treated 10 patients
with PAO including five with PPP skin manifestations with a
weekly GMA session over 5 weeks. Skin manifestations were
assessed using the PPP Area and Severity Index (PPPASI), and
joint symptoms were assessed using a visual analogue scale of
joint pain, tender joint count, swollen joint count and high-
sensitivity C-reactive protein immediately before, immediately
after, and at the 3-month follow-up of the five GMA sessions.
Two of five patients with PPP symptoms achieved > 50%
improvement in their PPPASI score (remarkably improved).
However, in two patients, deterioration of the skin symptoms
was noted, in one of whom the skin manifestations remained
unchanged at the 3-month follow-up. In five of the 10
patients with PAO, the joint symptoms were assessed as better
than ‘improved’ at the 3-month follow-up. No deterioration
was noted at the 3-month follow-up. In three patients, reduc-
tion or cessation of medication for arthralgia was possible
after GMA therapy. Based on these findings, we conclude that
GMA is a valid therapeutic option for patients with PAO.
P097Multicomponent biomarkers: a novel method foraccurate diagnosis of psoriasisF. L€attekivi,1 E. Reimann,1 M. Keermann,2,3
K. Abram,2,3 S. K~oks,1,4 K. Kingo2,3 and A. Fazeli1,51Department of Pathophysiology and 2Department of Dermatology, University
of Tartu, Tartu, Estonia; 3Clinic of Dermatology, Tartu University Hospital,
Tartu, Estonia; 4Department of Reproductive Biology, Estonian University of
Life Sciences, Tartu, Estonia and 5Academic Unit of Reproductive and
Developmental Medicine, Department of Oncology and Metabolism, The
Medical School, University of Sheffield, Sheffield, U.K.The accurate diagnosis of psoriasis has remained a challenge,
as no disease-specific biomarkers have yet been identified.
Currently, the diagnosis of chronic inflammatory diseases
relies mainly on the assessment of visible symptoms or the
histological features of the biopsy. This approach is heavily
reliant on the experience of the clinician and, therefore, may
lead to misdiagnosis as there are numerous different chronic
inflammatory skin diseases that may present similar clinical
features. Hence, the need for diagnostic biomarkers is clear.
Although different investigations have reported the discovery
of potential psoriasis biomarkers, still no accurate and reliable
biomarker is available. Rather than searching for a single valid
biomarker, we propose that applying a multicomponent bio-
marker-based approach would result in a higher degree of
success and translation into clinical practice. An extensive
review of published studies to identify the most relevant pso-
riasis-specific biomarker candidates was conducted. This led us
to conclude that the expression levels of specific genes in the
skin hold the most promise as discriminatory biomarkers,
resulting in the selection of five genes, the expression levels of
which have been demonstrated to be exclusive for psoriasis
vulgaris. We first conducted a preliminary validation study
applying support vector machine-based classification and prin-
ciple component analysis on the skin-derived expression data
of 12 patients with psoriasis vulgaris and 12 healthy controls,
previously produced in our departments. We then confirmed
that the expression levels of the five genes in psoriatic lesions
indeed present a unique pattern. Encouraged by these results,
we continued to develop a quantitative polymerase chain reac-
tion panel to allow the accurate measurement of expression
levels for the five genes to be used in the studies to follow.
Although we have yet to confirm these results in the context
of other chronic inflammatory skin diseases, the results of pre-
viously published studies regarding these five genes are
promising. Therefore, we are in the process of collecting addi-
tional skin samples from patients with chronic inflammatory
disease (including different papulosquamous disorders and
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
60 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
119ABSTRACTS
atopic dermatitis) to validate the discriminatory power of our
panel. These results may further be translated to viable clinical
diagnostic tests in the near future. This work was supported
by the ERA Chair for Translational Genomics and Personalized
Medicine at the University of Tartu.
P098Genome-wide DNA methylation profiling identifiesdifferential methylation in uninvolved psoriaticepidermisD. Verma, A.-K. Ekman, C.B. Eding and C. Enerb€ackIngrid Asp Psoriasis Center, Link€oping University, Link€oping, SwedenPsoriasis is a chronic inflammatory skin disease with both local
and systemic components. Genome-wide approaches have
identified more than 60 psoriasis-susceptibility loci, but genes
are estimated to explain only one-third of the heritability in
psoriasis, suggesting additional, yet unidentified, sources of
heritability. Epigenetic modifications have been linked to pso-
riasis, and altered DNA methylation patterns in psoriatic vs.
healthy skin have been reported in whole-skin biopsies. In this
study, focusing on epigenetic modifications in psoriatic unin-
volved skin, we compared the lesional and nonlesional epider-
mis from patients with psoriasis with epidermis from healthy
controls. We performed an exhaustive genome-wide DNA
methylation profiling using reduced representation bisulfite
sequencing, which interrogates the methylation status of
around 3–4 million CpG sites. More than 2000 strongly dif-
ferentially methylated sites (DMSs) were identified, and a
striking overrepresentation of the Wnt and cadherin pathways
among the DMSs was found. In particular, we observed a
strong differential methylation in several psoriasis candidate
genes. A substantial number of DMSs present in uninvolved
vs. healthy epidermis suggests the presence of a prepsoriatic
epigenetic signature. Our exploratory study represents a start-
ing point for identifying biomarkers for psoriasis-prone skin
before disease onset.
P099Gene expression changes induced by individualinterleukin (IL)-17 family cytokines signallingthrough IL-17RAD.A. Ewald, P. Lovato, T. Skak-Nielsen andH. NorsgaardLEO Pharma, Ballerup, DenmarkThe interleukin (IL)-23/IL-17 immune axis is of key impor-
tance for driving skin inflammation in psoriasis. However, the
importance of IL-17 family cytokines in psoriasis other than
IL-17A has not been fully elucidated. In this study, we investi-
gated the global transcriptional profile induced by IL-17 fam-
ily cytokine signalling through IL-17RA. For this purpose,
full-thickness punch biopsies of healthy skin were cultured in
the presence of individual IL-17 family cytokines for 24 h.
Gene expression profiling was carried out on whole-transcript
arrays (Affymetrix Human Gene 2.1 ST). We contrasted these
profiles with those of untreated controls, and compared the
resulting differential expression profiles with those of psoriatic
lesional vs. nonlesional skin. Ranked-list comparison and com-
parative gene set enrichment analysis indicated that the
IL-17A-, IL-17A/F- and IL-17F-induced expression profiles
most closely resemble the expression signature of psoriatic
skin. In comparison, the IL-17C-induced expression profile
overlaps to a lower degree with the psoriasis signature,
whereas the IL-17E-induced expression profile shows negligi-
ble overlap with the psoriasis signature. The global expression
findings were further confirmed by quantitative reverse-tran-
scriptase polymerase chain reaction on selected genes. The
expression of DEFB4A was strongly upregulated by IL-17A,
IL-17A/F and IL-17F, although with differences in potency.
IL-17C also increased the expression of DEFB4A but to a mark-
edly lower level, whereas IL-17E had no effect on the expres-
sion of DEFB4A. A comparable pattern was seen for other
IL-17-responsive genes, such as S100A7 and LCN2. In line with
these results, gene expression of DEFB4A in human primary
keratinocyte cultures was induced by IL-17A, IL-17F and
IL-17C in synergy with tumour necrosis factor-a to a high,
intermediate and low level, respectively. The induction of
DEFB4A by IL-17A, IL-17F and IL-17C was downregulated by
IL-17RA antagonism. The above findings indicate that IL-17A,
IL-17A/F and IL-17F, and to a lesser extent IL-17C, can all
induce gene expression changes similar to those observed in
psoriatic skin lesions. This suggests that combined inhibition
of IL-17 family cytokines, for example by targeting of the
IL-17RA receptor, could be a favoured mechanism for normal-
ization of the psoriasis-associated gene expression signature.
P100Validity of self-reported psoriasis in a Danish birthcohortC. Blegvad,1,2 T.E.T. Nielsen,1,2 C. Zachariae,1
A.-M.N. Andersen2 and L. Skov1
1Department of Dermatology and Allergy, Herlev and Gentofte Hospital,
University of Copenhagen, Copenhagen, Denmark and 2Section of Social
Medicine, Department of Public Health, University of Copenhagen,
Copenhagen, DenmarkSelf-reported disease is an inherent part of many register-based
studies. The validity of a self-reported diagnosis is therefore of
great importance. The aim of this study was to examine the
validity of self-reported psoriasis. As part of a larger clinical
study on children with psoriasis, we invited mothers and their
children for clinical examination. The mother–child pairs were
identified using a large birth cohort, the Danish National Birth
Cohort (DNBC), consisting of approximately 100 000 mothers
included via a telephone interview during pregnancy from
1997 to 2002. The mothers and their children have since been
followed up with internet-based questionnaires at child age 7
and 11 years. The mothers reported both their own psoriasis
status, at time of inclusion during pregnancy, and the child’s
psoriasis status, when the child was 11 years old. The ques-
tion to the mothers during pregnancy regarding their own
psoriasis status was whether they had ever been diagnosed
with psoriasis by a physician. The question to the mothers at
child age 11 years regarding the psoriasis status of their child
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 61
was whether the child had ever had an eruption of the skin
disease psoriasis. We invited the mother–child pairs in three
groups based on the psoriasis status given in the DNBC: ‘child
with psoriasis’, ‘mother with psoriasis’ and ‘healthy control’.
Maternal psoriasis status was confirmed on the basis of a his-
tory of physician-diagnosed psoriasis, on clinical appearance
where possible, and in case of doubt by consultation with a
senior dermatologist. Confirmation of psoriasis in the child
was done by means of a thorough clinical examination of the
skin in combination with anamnestic criteria. In case of doubt
a senior dermatologist was consulted. Fifty-eight children with
a positive DNBC psoriasis status were examined, and of these
only 28 (48%) could be confirmed as having psoriasis with
onset before the 11-year questionnaire. In regards to the
mothers, we could confirm the DNBC psoriasis status in 97
out of 120 (80.8%) from the ‘mother with psoriasis’ group.
Our study shows that the validity of self-reported psoriasis in
an adult female population is high in comparison with the
validity of the psoriasis status reported in their 11-year-old
children. The main reason for this is probably the use of
physician-diagnosed vs. self-diagnosed psoriasis. Furthermore,
psoriasis can be difficult to diagnose in children due to mild
symptoms.
P101Intentional and unintentional medicationnonadherence in psoriasis: the role of patients’medication beliefs and habit strengthR. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft,L. Cordingley and on behalf of the PSORT studygroup and BADBIRUniversity of Manchester and Manchester Academic Health Science Centre,
Manchester, U.K.Medication nonadherence is a missed opportunity for thera-
peutic benefit. Patients’ beliefs about their medication are key
drivers of nonadherence; however, there is a lack of high-
quality data on nonadherence to systemic therapies used for
psoriasis outside of clinical trials. As part of the Psoriasis Strati-
fication to Optimise Relevant Therapy (PSORT) consortium,
we assessed ‘real-world’ levels of self-reported nonadherence
to conventional and biological systemic therapies and evalu-
ated psychological and biomedical factors associated with non-
adherence using multivariable analyses. Cross-sectional data
from 811 patients with moderate-to-severe psoriasis using a
conventional systemic (35.3%) or biological therapy (64.7%)
were collected from 35 dermatology centres across England.
All patients were enrolled in the British Association of Derma-
tologists Biologic Interventions Register (BADBIR). A question-
naire assessed patients’ illness and medication beliefs (Revised
Illness Perception Questionnaire and Beliefs about Medicines
Questionnaire), psychological distress (Hospital Anxiety and
Depression Scale), the strength of the patient’s routine or habit
for using their medication (Self-Reported Habit Index) and
medication adherence (Medication Adherence Report Scale,
MARS), with a score ≤ 38 out of 40 on the MARS indicating
nonadherence. Patients’ biomedical data were obtained from
the registry. A significant proportion of patients using conven-
tional systemic (methotrexate, ciclosporin, acitretin, fumaric
acid esters) or biological therapies (etanercept, adalimumab)
were classified as nonadherent (22.4%); 12% were intention-
ally nonadherent, such as deliberately altering the dose, timing
or frequency of their therapy, and were 10.9% unintentionally
nonadherent, such as forgetting to use their therapy. Only
7.3% of patients using ustekinumab were classified as non-
adherent. Patients using a conventional systemic were signifi-
cantly more likely to be classified as nonadherent compared
with those using etanercept or adalimumab (29.2% vs. 16.4%;
P ≤ 0.001). After accounting for relevant variables, patients
who expressed the strongest concerns about their systemic
therapy and medicines in general were significantly more
likely to be classified as intentionally nonadherent (odds ratio
2.27, 95% confidence interval 1.16–4.47). Patients who
reported weaker routine or habit for using their therapy were
significantly more likely to be classified as unintentionally
nonadherent (odds ratio 0.92, 95% confidence interval 0.89–0.96). Medication nonadherence needs to be assessed when
determining factors influencing treatment response. Medica-
tion beliefs and habit strength are important modifiable targets
for strategies to improve adherence and clinical outcomes in
the management of psoriasis. C.E.M.G. is a National Institute
for Health Research Senior Investigator. PSORT is funded by
the Medical Research Council, grant MR/1011808/1.
P102Prognostic effect of psoriasis and psoriatic arthritisin patients with suspected coronary artery diseaseassessed by cardiac computed tomography:a multicentre cohort studyK.F. Hjuler,1 S. Winther,2 M. Bøttcher2 andL. Iversen1
1Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
and 2Department of Cardiology, Hospital Unit West, Herning, DenmarkEpidemiological population-based studies assessing cardiovas-
cular disease (CVD) in patients with psoriasis have been based
on registries containing diagnoses coded by clinicians. How-
ever, detailed clinical information is still needed about the
correlation between disease activity in both psoriasis and pso-
riatic arthritis (PsA) and the risk of CVD. This study was based
on data from a subregistry to the Western Denmark Heart
Registry (WDHR), the Western Denmark Cardiac Computed
Tomography Registry. This clinical registry contains informa-
tion on approximately 60 000 cardiac computed tomography
(CT) scans from 2008 to 2015 and has shown both high
completeness and high internal validity. Furthermore, WDHR
contains data on clinical information seldom available in reg-
istries. All nine sites collaborating in WDHR register patients
consecutively in a catchment area of 3.3 million inhabitants
(55% of the Danish population). The purpose of this study
was to acquire detailed clinical information on the association
between both psoriasis and PsA and coronary artery disease,
coronary interventions and major adverse cardiac events, in a
large population-based cohort. This cohort study included
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
62 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
121ABSTRACTS
39 125 patients [48.2% men; median age 57.6 years,
interquartile range (IQR) 49.1–65.6] with symptoms of coro-
nary artery disease (CAD), who underwent cardiac CT, of
whom 1325 (3.5%) were identified as having psoriasis
(45.6% men; median age 59.9 years, IQR 52.0–66.7) and
309 (0.8%) as having PsA (44.7% men; median age
58.4 years, IQR 52.2–63.1). The median duration of follow-
up was 2.8 years (IQR 1.3–4.5). The maximum duration of
follow-up was 8.4 years. The proportion of patients with vs.
without psoriasis with coronary artery calcium (CAC) score
> 0 was 47.5% [95% confidence interval (CI) 44.9–50.2] vs.
40.7% (95% CI 40.2–41.2). More patients with than without
psoriasis had luminal abnormalities (30.4% vs. 26.7%; differ-
ence between proportions 3.73%, 95% CI 1.24–6.23). The
proportion of patients with PsA vs. patients without psoriasis
with CAC score > 0 was 42.4% vs. 40.9%. The proportion of
patients with PsA with luminal abnormalities was not different
from that in patients without psoriasis. Myocardial infarction
occurred in 1.3% of patients with psoriasis and 2.6% of
patients with PsA vs. 0.9% of patients without psoriasis. The
composite end point occurred in 8.4% of patients with psoria-
sis and 10.0% of patients with PsA vs. 7.4% of patients with-
out. Compared with patients without psoriasis, a higher
relative risk of the composite end point was observed for
patients with psoriasis [hazard ratio (HR) 1.16; 95% CI 0.95–1.41] and PsA (HR 1.41, 95% CI 0.98–2.02). However, in
psoriasis, the risk was reduced after adjustment for CVD risk
factors (HR 1.05, 95% CI 0.86–1.27), whereas it remained
significantly increased in patients with PsA (HR 1.50, 95% CI
1.04–2.14). In conclusion, this study based on unique data
from a large population-based cardiac CT registry showed that
the extent of CAD was increased in patients with psoriasis,
whereas the risk of CVD events was not increased. Despite
only slightly increased CAD, the risk of CVD events was
increased in patients with PsA.
P103Safety of guselkumab in patients with plaquepsoriasis through 2 years: a pooled analysis fromVOYAGE 1 and VOYAGE 2K. Reich,1 K. Papp,2 A.W. Armstrong,3 Y. Wasfi,4
G. Jiang,4 Y.-K. Shen,4 B. Randazzo,4 M. Song4 andA.B. Kimball51Dermatologikum Hamburg and SCIderm Research Institute, Hamburg,
Germany; 2K. Papp Clinical Research and Probity Medical Research,
Waterloo, ON, Canada; 3University of Southern California, Los Angeles, CA,
U.S.A.; 4Janssen Research & Development, LLC, Spring House, PA, U.S.A.
and 5Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical
Center, Inc., Boston, MA, U.S.A.We evaluated the safety of guselkumab in patients with mod-
erate-to-severe psoriasis from the VOYAGE 1 and 2 studies
through 2 years. In the phase III, randomized, double-blind,
placebo/active comparator-controlled VOYAGE 1 (n = 837)
and VOYAGE 2 (n = 992) trials, patients (age ≥ 18 years) had
plaque psoriasis for ≥ 6 months, Investigator’s Global Assess-
ment scores ≥ 3, Psoriasis Area and Severity Index scores ≥
12, ≥ 10% body surface area involvement, and were candi-
dates for systemic or phototherapy. Patients were randomized
to guselkumab, placebo or adalimumab at baseline. Placebo
patients crossed over to receive guselkumab at week 16 and
adalimumab patients crossed over to receive guselkumab
either at week 52 (VOYAGE 1) or week 28 or beyond (VOY-
AGE 2). Here we present safety data (event rates adjusted for
follow-up: per 100 patient-years) through 2 years for patients
who were initially randomized to guselkumab and those who
were randomized to placebo and crossed over to guselkumab
at week 16. Among the guselkumab-treated patients, overall
safety event rates were comparable through year 1 and cumu-
latively through year 2. Additionally, safety data from patients
on adalimumab who crossed over to guselkumab were consis-
tent with the overall guselkumab safety data, with no addi-
tional safety signals identified. In conclusion, the safety profile
of guselkumab through up to 2 years of continuous treatment
was consistent with that observed through 1 year.
Guselkumab 100 mg Year 1 Year 2
Patients 1221 1221
Total patient-yearsof follow-up
974 2084
Common AEsper 100
patient-yearsof follow-up
259.42 210.41
Nasopharyngitis 32.84 26.78Upper respiratory
tract infection
17.24 14.11
Bronchitis 3.49 2.69AEs leading to
discontinuation
2.36 1.82
Serious AEs 6.05 6.29
Infections 97.69 81.74Infections requiring
treatment
26.48 23.76
Serious infections 1.03 1.06
Malignancies(excluding NMSC)a
0.31(0.06–0.90)
0.38(0.17–0.76)
Non-melanomaskin cancer
(NMSC)a
0.62(0.23–1.34)
0.39(0.17–0.76)
MACEa 0.41
(0.11–1.05)0.38
(0.17–0.76)
Values are reported as event rates per 100 patient-years. AE,
adverse event; MACE, major adverse cardiac event; NMSC, non-
melanoma skin cancer. aWith 95% confidence interval.
P104Additional efficacy benefit of continuousixekizumab every-2-week dosing among patientswith psoriasis who do not respond by week 12K. Papp,1,2 M. Gooderham,3 P. Polzer,4 L. Zhang4
and M. Augustin5
1K. Papp Clinical Research, Waterloo, ON, Canada; 2Probity Medical
Research, Waterloo, ON, Canada; 3Queen’s University, SKiN Centre for
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 63
Dermatology, Peterborough, ON, Canada; 4Eli Lilly and Company,
Indianapolis, IN, U.S.A. and 5Institute for Health Services Research in
Dermatology and Nursing, University Medical Center, Hamburg, GermanyIxekizumab, an interleukin (IL)-17A antagonist, previously
demonstrated long-term efficacy and safety in pivotal phase III
trials. However, these trials did not contain long-term contin-
uous every-2-week (Q2W) dosing, which may benefit those
patients who do not respond by week 12. Thus, we evaluated
efficacy through 52 weeks in static Physician’s Global Assess-
ment (sPGA) 0/1 responders and nonresponders in IXORA-P,
which included a continuous Q2W dosing group through
week 52. In IXORA-P (NCT02513550), a phase III, multicen-
tre, randomized, double-blinded trial, patients with moderate-
to-severe plaque psoriasis were randomized at a 2 : 1 : 1 ratio
to three dosing regimens of 80-mg ixekizumab: continuous
Q2W (n = 611), continuous Q4W (n = 310) or Q4W/Q2W
dose adjustment per protocol (n = 306), each with a 160-mg
starting dose. Dose adjustment from Q4W to Q2W was deter-
mined by predefined criteria to which investigators were
blinded (72 patients, 23.5%, dose adjusted). Data from
patients who were nonresponders at week 12 (defined by
sPGA > 1) and received ixekizumab Q2W/Q4W (n = 65) or
continuous Q4W (n = 225) in the three UNCOVER trials
(NCT01474512, NCT01597245 and NCT01646177) were
integrated through 52 weeks. Missing data were imputed
using nonresponder imputation. The Bucher indirect compar-
ison method was used to compare continuous Q2W (IXORA-
P) and current label dose of Q2W/Q4W (UNCOVER trials),
with a common comparator of continuous Q4W. In IXORA-P,
81%, 67% and 73% of patients in the Q2W, Q4W and Q4W/
Q2W dose adjustment groups, respectively, were sPGA 0/1
responders at week 12. Among the responders at week 12,
85%, 86% and 82% of patients in the Q2W, Q4W and Q4W/
Q2W dose adjustment groups, respectively, maintained sPGA
0/1 response at week 52. Among the nonresponders at week
12, 64%, 42% and 52% of patients in the Q2W, Q4W and
Q4W/Q2W dose adjustment groups, respectively, achieved
sPGA 0/1 response at week 52, while the response for the
Q4W group (42%) was comparable with that in the inte-
grated UNCOVER Q4W/Q4W group (44%). The sPGA 0/1
response at week 52 was significantly higher in the IXORA-P
continuous Q2W group (64%) than in the integrated
UNCOVER Q2W/Q4W group (36%, P < 0.001) with Bucher
indirect comparison. There were no clinically relevant differ-
ences in regard to safety between responders and nonrespon-
ders. Overall, sPGA 0/1 responses at week 52 were similar
across all dosing groups among patients who were responders
at week 12. Among patients who were nonresponders at week
12, sPGA 0/1 responses were higher at week 52 in patients
treated continuously with Q2W compared with patients trea-
ted continuously with Q4W in the IXORA-P trial, and also
when compared indirectly with week 12 nonresponders trea-
ted with Q2W/Q4W (label dose) in the integrated UNCOVER
trials.
P105Absolute Psoriasis Area and Severity Indeximprovement through 2 years of guselkumabtreatment in the VOYAGE 1 trial of patients withplaque psoriasisK. Papp,1 C.E.M. Griffiths,2 A.B. Kimball,3 S. Li,4
Y.-K. Shen,4 Y. Wasfi4 and A. Blauvelt5
1K. Papp Clinical Research and Probity Medical Research, Waterloo, ON,
Canada; 2Dermatology Centre, Salford Royal Hospital, University of
Manchester, Manchester Academic Health Science Centre, Manchester, U.K.;3Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA,
U.S.A.; 4Janssen Research & Development, LLC, Spring House, PA, U.S.A.
and 5Oregon Medical Research Center, Portland, OR, U.S.A.The study objective was to assess efficacy responses based on
absolute Psoriasis Area and Severity Index (PASI) improvement
through 2 years of guselkumab treatment in the VOYAGE 1
trial. VOYAGE1 is a phase III, randomized, double-blinded,
placebo–active comparator-controlled trial. Eligible patients
(age ≥ 18 years) had moderate-to-severe plaque psoriasis for
≥ 6 months, an Investigator’s Global Assessment score ≥ 3,
PASI score ≥ 12, ≥ 10% body surface area involvement, and
were candidates for systemic or phototherapy. In total 837
Skin response by PASI category through week 100, %
Placebo Guselkumab Adalimumab
Randomized
patients
174 329 334
PASI score
categoriesWeek 16 174 329 334
0 0.6 37.4; P < 0.001c 17.1; P < 0.001c
≤ 1 5.2 60.5; P < 0.001c 35.3; P < 0.001c
≤ 3 6.9 84.8; P < 0.001c 64.4; P < 0.001c
Week 24a 165 329 334
0 22.4 44.4 24.9; P < 0.001d
≤ 1 35.2 69.9 41.9; P < 0.001d
≤ 3 67.9 90.9 68.3; P < 0.001d
Wk48a 165 329 334
0 50.3 47.4 23.4; P < 0.001d
≤ 1 66.7 72 43.4; P < 0.001d
≤ 3 94.5 89.4 66.2; P < 0.001d
Week 76a,b 159 300 276
0 53.5 56.3 53.3
≤ 1 75.5 71 70.3≤ 3 95.6 89.7 93.5
Week 100a,b 158 290 2750 55.1 49 51.6
≤ 1 70.9 68.6 69.8≤ 3 93 88.3 88.7
Through week 48, nonresponder imputation was used for missing
data after applying treatment failure rules. From weeks 52 to 100,
observed data were used after applying treatment failure rules.aAmong placebo-randomized patients, includes only those crossing
over to guselkumab after week 16. bAmong adalimumab-rando-
mized patients, includes only those crossing over to guselkumab
after week 52. cP-values based on comparisons vs. placebo. dP-
values based on guselkumab vs. adalimumab.
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
64 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
123ABSTRACTS
patients were randomized (2 : 1 : 2) to guselkumab 100 mg
at weeks 0, 4 and 12, then every 8 weeks; placebo at weeks
0, 4 and 12 followed by guselkumab 100 mg at weeks 16
and 20 then every 8 weeks; or adalimumab 80 mg at week 0,
40 mg at week 1 then 40 mg every 2 weeks through weeks
47, followed by guselkumab at week 52 then every 8 weeks.
Efficacy data through week 100 based on absolute PASI
response thresholds of 0, 1 and 3 (Table) were derived as an
ad hoc analysis. Absolute PASI response rates were significantly
higher for guselkumab vs. placebo at week 16 and vs. adali-
mumab at weeks 24 and 48. Among adalimumab-randomized
patients, PASI responses were substantially higher by week 76
following crossover to guselkumab at week 52. Skin response
levels were maintained through 2 years among guselkumab-
treated patients (Table). In conclusion, guselkumab treatment
provided significantly higher absolute PASI responses than
adalimumab through 1 year, and robust skin responses were
maintained through 2 years with continuous guselkumab
treatment.
P106Guselkumab treatment results in more effectiveand durable inhibition of T helper (Th)17 and Th22cells and downstream effectors compared withadalimumabX. Liu,1 P.J. Branigan,2 Y. Chen,1 S. DePrimo,1
K. Campbell2 and E.J. Munoz11Janssen Research & Development, LLC, San Diego, CA, U.S.A. and 2Janssen
Research & Development, LLC, Spring House, PA, U.S.A.Psoriasis is an interleukin (IL)-23-driven T-cell-mediated
inflammatory skin disease. Guselkumab (GUS) is a fully
human IgG1k monoclonal antibody that selectively binds and
blocks IL-23. In VOYAGE 1, a phase III study in patients with
moderate-to-severe chronic plaque psoriasis, GUS demon-
strated superior efficacy over adalimumab (ADA), a tumour
necrosis factor (TNF)-a inhibitor. To understand further their
underlying molecular mechanisms of action, microarray data
were generated from skin biopsies obtained at baseline and at
4, 24 and 48 weeks after initiation of GUS (n = 17) or ADA
(n = 12) treatment. GUS- and ADA- mediated normalization
of disease-associated gene expression was evaluated for a list
of curated immune/skin inflammation gene sets related to T
helper (Th)17, Th22, Th1, T regulatory cell (Treg), immune-
activated macrophage, dendritic cell, keratinocyte and epithe-
lial cell profiles. Gene set variation analysis (GSVA) was
applied to evaluate disease- and treatment-associated differen-
tial expression at the whole gene set level. In total 81 of 131
gene sets were enriched with differentially expressed genes at
baseline (lesional vs. nonlesional). In each of these 81 gene
sets, more genes were normalized by GUS than ADA at all
time points, with the greatest differences seen at week 48. At
4 weeks, 12 vs. 0 gene sets showed > 50% of genes with
> 75% improvement for GUS and ADA, respectively. At
48 weeks, 75 vs. 0 gene sets showed > 50% of genes with
> 90% improvement for GUS and ADA, respectively. The top
20 gene sets showing improvement included Th17-specific
genes, Treg-upregulated genes and IL17-, IL22-, IL17-/IL22-,
IL17- and TNF-a-induced genes in keratinocytes. GSVA con-
firmed 74 out of 81 gene sets and identified 40 additional
gene sets that were differentially expressed at baseline, includ-
ing a T-cell-receptor complex gene set that was more effi-
ciently normalized by GUS. Overexpression of T-cell-receptor
genes (TCRA, TCRB, CD3) was normalized with GUS by 20%,
62% and 102% at weeks 4, 24 and 48 compared with �19%,
25% and 21% by ADA, respectively. These data suggest that
the higher clinical responses observed with GUS compared
with ADA may result from more effective and durable inhibi-
tion of T cells, especially Th17 and Th22 cells, and down-
stream effects on keratinocytes.
P107Cost of topical therapies for patients with psoriasisin GeorgiaK. Tsagareishvili1 and N. Chijavadze21Akaki Tsereteli State University, Kutaisi, Georgia and 2Psoriasis Association
of Georgia (PSO Georgia), Kutaisi, GeorgiaPsoriasis is a chronic disease requiring prolonged treatment at
high cost. The goal of our research was to find out the cost of
topical treatment of the patients with mild-to-moderate psori-
asis and its impact on their monthly income. For this purpose
103 patients with psoriasis were interviewed including 47
(45.2%) female and 55 (54.8%) male, with 65 (63.1%) from
urban and 38 (38.9%) from rural populations. Overall 74% of
the patients were age 25–76 years. The diagnosis in 97.9% of
patients was mild-to-moderate chronic plaque psoriasis with
an affected body surface area < 10%. These patients used only
self-treatment with topic medications and had poor contact
with their dermatologists. The questionnaire included the type
and amount of topical medications used by the patients with
psoriasis, the frequency of showering, their skincare products
and their monthly income. The results showed that 99%
(102) of the patients used only the strongest strength of topi-
cal steroid – clobetasol propionate 0.05% (available over the
counter in Georgia) – not only for the period of exacerbation
but also during the remission to prolong it, using four to five
tubes (each 25 g) per month. At the same time as the topical
corticosteroid treatment, only 15 patients (14.6%) used other
topical medicines (calcipotriol 50 mg + betamethasone
500 mg ointment, coal tar solution 5%) because of their high
costs. The majority of the patients (71.4%, 74) did not use
skincare products; 70.6% of the patients showered every day
and 29.4% showered two to three times per week. The aver-
age income of the interviewed patients of the different income
groups varied from 72 USD (180 GEL) to 400 USD (1000
GEL). Accordingly the expenses of topical corticosteroid treat-
ment were highest among pensioners (16.7%), and 3–6%among the other groups. The low income of the patients, the
availability of over-the-counter topical corticosteroids in Geor-
gia, their low costs compared with other topical medicines
and their effectiveness determine the priority of their usage.
According to the National Statistics Office of Georgia, 21.3%
of the population was under the absolute poverty line in
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 65
2016, therefore further study of economic impact of the treat-
ment of psoriasis in Georgia would provide data on the
disease burden on society.
P108Looking beyond 12 weeks: long-term drug survivaland safety of secukinumab in real-world patientswith plaque psoriasisJ.R. Georgakopoulos,1 A. Ighani,2 M. Phung3 andJ. Yeung4,51Schulich School of Medicine and Dentistry, Western University, London,
ON, Canada; 2Faculty of Medicine, University of Toronto, Toronto, Canada;3Department of Pharmacology and Toxicology, University of Toronto,
Toronto, ON, Canada; 4Division of Dermatology, Faculty of Medicine,
University of Toronto, Toronto, ON, Canada and 5Probity Medical Research
Inc., Waterloo, ON, CanadaFrom early findings identifying interleukin (IL)-17A as a plau-
sible target in the immunopathogenic mechanism of psoriasis
to phase III randomized controlled trials (RCTs) demonstrating
secukinumab to be highly efficacious and safe, much excite-
ment has surrounded the approval of the first IL-17A antago-
nist. However, at this time, no study has looked at long-term
outcomes for real-world patients with psoriasis, who are
believed to be more challenging to treat than those enrolled
in RCTs. We aimed to investigate the efficacy and safety of
secukinumab at week 52 or the time of treatment discontinua-
tion for individuals who were Psoriasis Area and Severity
Index (PASI) 75 responders at week 12. These findings will
provide much-needed insight into whether real-world patients
with psoriasis achieve similar long-term outcomes to individu-
als enrolled in RCTs. A multicentre retrospective chart review
was conducted using data from medical records of adult
patients treated with secukinumab 300 mg for plaque psoria-
sis. Efficacy [PASI 75 or Physician’s Global Assessment (PGA)
of 0 or 1] and safety (reported adverse events) were assessed
following 12- and 52-week treatment periods or at the time
of discontinuation. Forty-one patients had moderate-to-severe
plaque psoriasis, achieved PASI 75 or PGA 0/1 at week 12
and were followed up to week 52 or the time of secukinumab
discontinuation, and thus were included in our analysis.
Twenty-eight (68%) maintained PASI 75 or PGA 0/1 at week
52. Of the 13 (32%) patients who did not achieve efficacious
outcomes at week 52, two (5%) experienced loss of efficacy
(< PASI 75) and 11 (27%) stopped treatment prior to week
52 due to lack of efficacy (n = 10, 24%) or intolerance
(n = 1, 2%). The mean treatment duration for individuals
who discontinued treatment between weeks 12 and 52 was
40.0 weeks (range 26.1–51.0). Additionally, adverse events
after week 12 were documented in 17% (n = 7) of patients.
Commonly reported adverse events included diarrhoea (n = 2,
5%) and respiratory tract infection (n = 2, 5%). Our results
suggest that fewer patients with psoriasis in real-world clinical
practice maintain efficacious outcomes at week 52 than those
enrolled in RCTs. Furthermore, discontinuation of treatment
appears to occur around week 40, similarly to time of treat-
ment discontinuation seen with older biological therapies.
Overall, these findings will greatly improve dermatologists’
ability to monitor secukinumab efficacy and safety beyond
week 12.
P109Efficacy and safety of ixekizumab in secukinumabnonresponders: therapeutic options for nonanti-interleukin-17A-naive patientsJ.R. Georgakopoulos,1 M. Phung,2 A. Ighani3 andJ. Yeung4,51Schulich School of Medicine and Dentistry, Western University, London,
ON, Canada; 2Department of Pharmacology and Toxicology, University of
Toronto, Toronto, ON, Canada; 3Faculty of Medicine, University of Toronto,
Toronto, ON, Canada; 4Division of Dermatology, Faculty of Medicine,
University of Toronto, Toronto, ON, Canada, 5Probity Medical Research Inc.,
Waterloo, ON, CanadaThe discovery of type 17 helper T (Th17) cells and their
release of the proinflammatory cytokine interleukin (IL)-17A
has shown that they play a central role in the autoimmune
inflammatory cascade and phenotypic changes associated
with psoriasis. New biological agents, secukinumab and
most recently ixekizumab, have been developed that bind to
IL-17A and neutralize the bioactivity of this cytokine. While
both have been vigorously studied in isolation, no study
has looked at outcomes when switching between these two
treatments, which have similar therapeutic targets. This is of
interest, as biological switching has become a common
practice in dermatology clinics. Consequently, we aimed to
assess the efficacy and safety of ixekizumab in real-world
patients with plaque psoriasis who have previously failed
secukinumab therapy. From secukinumab drug approval
until July 2017, we performed a multicentre retrospective
chart review of consecutive patients with psoriasis treated
with secukinumab 300 mg. Patients who were 18 years of
age or older with moderate-to-severe plaque psoriasis and
treated with ixekizumab 80 mg (160 mg at week 0, fol-
lowed by 80 mg every 2 weeks starting week 2), immedi-
ately following discontinuation of secukinumab due to lack
of efficacy or intolerance, were eligible for inclusion. Of
the 16 patients who met the inclusion criteria, 13 (81%)
achieved ≥ 75% improvement in Psoriasis Area and Severity
Index (PASI 75) after 12 weeks of ixekizumab treatment.
The mean PASI at secukinumab baseline was 13.0 � 4.7; it
was 11.0 � 3.4 at the time of switching and 1.6 � 3.6 at
ixekizumab week 12. Five (31%) patients experienced one
or more nonserious adverse event, including injection-site
reaction (n = 3, 19%), elevated liver enzymes (n = 1, 6%)
and drug eruption with lymphocytic and eosinophilic infil-
trates secondary to secukinumab (n = 1, 6%). Discontinua-
tion of treatment due to an adverse event was uncommon,
with just one patient (6%) stopping due to a prolonged
drug eruption secondary to secukinumab. Despite the inher-
ent limitation in our sample size, this is the first report of
the efficacy and safety of ixekizumab in nonanti-IL-17A-
naive patients. Our findings suggest that ixekizumab appears
to be a promising efficacious treatment option for
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
66 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
125ABSTRACTS
secukinumab nonresponders and is associated with a clini-
cally acceptable rate of adverse events.
P110Long-term, real-world efficacy of infliximab forpsoriasisL. Mercieca, R.B. Warren and C.E.M. GriffithsDermatology Centre, Salford Royal Hospital, University of Manchester,
Manchester, U.K.Infliximab has been licensed for the management of severe
psoriasis since 2006. There are limited data on its long-term,
> 6-year, efficacy. The aim of this study is to report long-
term, real-world clinical data of patients with psoriasis on
infliximab. A single-centre retrospective observational study
was conducted. Patients with psoriasis maintained on inflix-
imab for 6 years or longer were included. Clinical data,
including Psoriasis Area and Severity Index (PASI) and Derma-
tology Life Quality Index (DLQI), were collected prior to start-
ing infliximab and at each subsequent outpatient visit. A total
of 11 patients with psoriasis (seven male and four female)
with an average age of 54.5 years (range 43–81) were main-
tained on infliximab at 5 mg kg�1 every 6–8 weeks (average
7.6) for ≥ 6 years. The average age of onset of psoriasis was
24.2 years (range 11–61) and nine had psoriatic arthritis. The
most common comorbidities, other than psoriatic arthritis,
were hypertension, cardiovascular disease and ankylosing
spondylitis. Infliximab was started between 2005 and 2011
with a mean treatment duration of 9.2 years (range 6–12).The mean baseline PASI and DLQI scores were 22.4 and 18,
respectively. At years 1, 4, 8 and 12 the respective mean PASI
scores were 4.6, 1.9, 2.3 and 2.4, while the mean DLQI
scores were 3, 3, 4 and 4, respectively. There were no serious
side-effects reported, with recurrent respiratory and skin infec-
tions being the most common. Most patients flared up after
postponing treatment due to surgery, infections or time
abroad, and three patients were on concomitant low-dose
methotrexate (average dose 10 mg per week). To our knowl-
edge this is the longest reported study on patients with psoria-
sis maintaining efficacy and safety on infliximab for up to
12 years. Further studies are needed to elucidate why these
patients continue to have control of their psoriasis on long-
term infliximab.
P111Fine mapping and subphenotyping implicatesADRA1B gene variants in psoriasis in a ChinesepopulationX. Fan,1,2,3 H. Wang,1,2,3 L. Sun,1,2,3 X. Yin,1,2,3
X. Zuo,1,2,3 Q. Peng,4 K. A. Standish,5,6 X. Zheng,1,2,3
Z. Wang,1,2,3 F. Xiao,1,2,3 S. Yang,1,2,3 X. Zhang12,3
and N.J. Schork51Institute of Dermatology, Anhui Medical University, Hefei, China; 2Key Lab
of Dermatology, Ministry of Education, Anhui Medical University, Hefei,
China; 3Department of Dermatology, The First Affiliated Hospital of Anhui
Medical University, Hefei, China; 4Department of Molecular and
Experimental Medicine, The Scripps Research Institute, La Jolla, CA, U.S.A.;
5Human Biology, J. Craig Venter Institute, La Jolla, CA, U.S.A. and6Biomedical Sciences Graduate Program, University of California, San Diego,
La Jolla, CA, U.S.A.Previous genome-wide association studies (GWASs) have iden-
tified more than 40 independent genome-wide significant pso-
riasis susceptibility loci. We identified a genomic region on
5q33.3 harbouring variants associated with psoriasis in our
own GWAS and replication between the IL12B and PTTG1
genes. However, there are many potential causal variants in
this genomic region. To examine further the influence of vari-
ants in and around this region, we used the 1000 Genome
reference haplotypes to impute additional variants in the
region in our study samples to increase the marker density in
this region to 2171 genetic variants. We then used lasso-based
regression analysis to assess the independent contributions of
these variants to psoriasis and found evidence of association
for 62 of the 2171 single-nucleotide polymorphisms (SNPs)
in this region (seven SNPs around IL12B, 12 SNPs around
PTTG1 and 43 SNPs between the two genes). To evaluate these
62 SNPs further, we tested them for association with different
clinical psoriasis subtypes, psoriasis severity and psoriasis age
of onset. These analyses revealed slight differences between
the SNPs exhibiting associations based on the whole case–con-trol analysis and the subphenotype, cases-only analysis. The
most significant locus with the largest number of SNPs was
located in the ADRA1B gene, which is between the IL-12B and
PTTG1 genes in the 5q33.3 region. Variants in ADRA1B were
most strongly associated with the plaque subgroup, and
showed a stronger association with the moderate-to-severe
skin disease group and an earlier age at onset of psoriasis.
Using genome-wide complex trait analysis, the four indepen-
dently associated loci in the ADRA1B gene in total explained
39.5% of the phenotype variance of psoriasis under the
assumption of psoriasis prevalence of 0.2%. This highlights
the contribution of ADRA1B to psoriasis in the Chinese popula-
tion. We found no evidence to support the notion that vari-
ants in the IL12B and PTTG1 genes are associated with age of
onset of psoriasis in our study, suggesting that the IL12B and
PTTG1 genes might have only a weak relation to psoriasis.
However, we did find evidence that variants in the ADRA1B
gene residing between IL12B and PTGG1 are associated with
psoriasis. This could explain why variants in the region have
been found to be associated with psoriasis previously,
although more studies confirming this should be pursued.
P112Retrospective study of childhood psoriasisM.S. Zorko and O. TockovaUniversity Medical Centre Ljubljana, Ljubljana, SloveniaPsoriasis is a chronic immune-mediated inflammatory skin dis-
ease that occurs in about 3.5% of the general population. It
begins in childhood in approximately one-third of the cases.
Most children manifest with plaque-type psoriasis vulgaris,
and the most common trigger is an upper respiratory tract
infection. Up to 71% of children have a family history of pso-
riasis. Paediatric psoriasis can been associated with certain
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 67
comorbidities, such as obesity, hypertension, hyperlipidaemia,
diabetes mellitus and rheumatoid arthritis. Treatment is deter-
mined based on the severity of the disease and remains a chal-
lenge. We performed a retrospective study of children with
psoriasis, aged under 16 years, who have been hospitalized at
our clinics between 2013 and 2016. In total 24 children with
moderate-to-severe psoriasis (median Psoriasis Area and Sever-
ity Index 17.2 at the beginning of the hospitalization) were
hospitalized at our clinics between 1 January 2013 and 31
December 2016. It represented 3% of all dermatoses seen in
hospitalized children under the age of 16 years. Sixteen (67%)
patients had classic plaque psoriasis, five (21%) had guttate
psoriasis and three (12%) had other types of psoriasis (palmo-
plantar psoriasis, inverse psoriasis, psoriasis of the nails and
scalp). In four of the five children with guttate psoriasis,
streptococcal infection preceded the onset. A positive family
history of psoriasis (first- and second-degree relatives) was
present in 13 (54%) children. Comorbidities like arterial
hypertension, diabetes, hyperlipidaemia and arthritis, most
commonly described, were not found in our patients. Among
16 children with a resistant form of plaque psoriasis, seven
were treated with methotrexate and three with narrowband
ultraviolet B phototherapy. We observed good response to the
therapy and no serious side-effects (mean Psoriasis Area and
Severity Index 3.5 at the end of hospitalization). As previously
described in the literature, plaque psoriasis is the most com-
mon type of psoriasis in children, and this was also seen in
our study. The guttate form was the second most common
type and it was mostly associated with streptococcal infection.
Comorbidities, most commonly associated with psoriasis, were
not found in our young patients. Based on our experience,
narrowband ultraviolet B and systemic therapy with
methotrexate are valuable, safe and effective treatments in the
moderate-to-severe form of therapy-resistant psoriasis in chil-
dren. However, more evidence-based data are needed about
the effectiveness and long-term safety of such therapies in
children.
P113Immature progenitor cells are enriched in psoriasisepidermisA.-K. Ekman, C.B. Eding, I. Rundquist andC. Enerb€ackIngrid Asp Psoriasis Research Center, Link€oping University, Link€oping, SwedenPsoriasis is a chronic inflammatory skin disorder characterized
by a marked hyperproliferation of basal epidermal cells. It is
regarded as a T-cell-mediated disorder, but the role of ker-
atinocytes in the disease pathogenesis has re-emerged with
genetic studies identifying several keratinocyte-specific genes.
We have applied multicolour flow cytometry on epidermal
keratinocytes isolated from involved and uninvolved epidermis
to characterize the cellular phenotype of these proliferative
cells and to compare the cell subpopulations further. We iden-
tified a strikingly reduced percentage of cells positive for the
early differentiation marker cytokeratin 10 (K10), combined
with increased fractions of CD29+ and involucrin-positive cells
in psoriasis keratinocytes compared with normal cells. The
psoriasis keratinocytes also displayed an overall increased
expression of the stemness markers p63 (sevenfold), CD44
(2.7-fold) and CD29 (2.2-fold). Interestingly, these differ-
ences were primarily confined to K10+ cells. We hypothesized
that stimuli present in the psoriatic micromilieu may con-
tribute to the cellular immaturity. In normal keratinocytes, we
found that interleukin-22 increased the expression of p63,
CD44 and CD29 at both the mRNA and protein levels. Taking
the evidence together, we describe an overall more immature
phenotype of psoriasis keratinocytes compared with normal
keratinocytes, with an altered frequency of several subpopula-
tions and a distinct marker expression within these subpopula-
tions. This immature stem cell-associated phenotype is likely
to impact the cell proliferation and premature terminal differ-
entiation in psoriasis. Furthermore, our data suggest that inter-
leukin-22 links immunity to epithelial regeneration by acting
directly on keratinocytes to promote stemness.
P114PRINS long noncoding RNA regulates theexpression of interleukin-6 and CCL-5 by directinteractionJ. Danis,1,2 A. G€obl€os,1,2 L. Janov�ak,2
Z. Bata-Cs€org}o,1,2 L. Kem�eny12 and M. Szell1,31MTA-SZTE Dermatological Research Group, Szeged, Hungary and2Department of Dermatology and Allergology and 3Department of Medical
Genetics, University of Szeged, Szeged, HungaryCytosolic DNA fragments represent pathogen and danger-asso-
ciated molecular patterns and induce a cascade of innate
immune responses in cells. Excessive cytosolic DNA can
enhance chronic inflammation predominantly by activating
inflammasomes, thereby contributing to the pathogenesis of
chronic inflammatory diseases such as psoriasis. Psoriasis-asso-
ciated nonprotein-coding RNA induced by stress (PRINS) is a
long noncoding RNA, which has already been associated with
psoriasis susceptibility and cellular stress response; however,
its precise mechanism has been less studied. Recently, its regu-
latory role in the expression of the chemokine, CCL-5, was
reported, suggesting its anti-inflammatory function. The aim
of this study was to identify the role of PRINS in psoriasis-
associated inflammatory reactions, which could explain the
importance of its high expression in psoriatic uninvolved epi-
dermis. Transfection of the synthetic DNA analogue poly(dA:
dT) was used to induce inflammatory reactions in normal
human epidermal keratinocytes (NHEKs), and expression of
inflammatory cytokines was measured by real-time reverse-
transcriptase polymerase chain reaction and enzyme0linked
immunosorbent assay. Poly(dA:dT) induced the expression of
interleukin (IL)-1a, IL-b, IL-6, IL-8, IL-23 an tumour necrosis
factor (TNF)-a, and pretreatment with combined TNF-a and
interferon-c increased their expression further. The treatment
decreased the expression of PRINS in NHEKs. Overexpression
of PRINS during the treatment resulted in decreased IL-6
expression. CCL-5, showing a similar expression pattern to
IL-6, was recently shown to be directly regulated by PRINS, so
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
68 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
127ABSTRACTS
we proposed a similar mechanism for IL-6 regulation. We
performed an in silico analysis and found a 100-nucleotide-long
possible interaction site between the mRNA of IL6 and PRINS.
An in vitro binding assay confirmed this predicted interaction
with a very high affinity of PRINS binding to IL6 mRNA
(Kd = 10.34 nmol L�1). To validate the functionality of this
interaction on the cellular level we created a DPRINSsequence, containing a scrambled sequence on the possible IL6
interaction, site and performed the overexpression experiment
with DPRINS. While PRINS decreased the expression of IL6,
DPRINS did not show the same effect; however, the level of
CCL-5 (having a different interaction site) decreased to the
same level after overexpression of PRINS or DPRINS. Based on
our results we propose that PRINS acts as a regulator for both
IL-6 and CCL-5. These results link PRINS to inflammatory pro-
cesses, and indicate the significance of its higher expression in
psoriatic uninvolved epidermis. Funding: K111885, GINOP-
2.2.1-15-2016-00007 and GINOP-2.3.2-15-2016-00015.
P115CARD14 variants in pityriasis rubra pilarisA. G€obl€os,1,2 J. Danis,1,2 B. G�al,1 K. Farkas,3
E. Varga,1 I. Korom,1 L. Kem�eny,1,2 N. Nagy,3
M. Sz�ell23 and Z. Bata-Csorg}o1,21Department of Dermatology and Allergology and 3Department of Medical
Genetics, University of Szeged, Szeged, Hungary and 2MTA-SZTE
Dermatological Research Group, Szeged, HungaryPityriasis rubra pilaris (PRP) is a rare, papulosquamous skin
disorder with important inflammatory features. PRP is pheno-
typically related to psoriasis. CARD14 single-nucleotide variants
(SNVs) have been described in both diseases, and documented
gain-of-function CARD14 mutations suggest its role in the dis-
ease pathomechanism. We screened 15 patients with sporadic
PRP and one with familial PRP for SNVs in the CARD14 gene.
In the patient with familial PRP we identified three genetic
variants (rs117918077, rs2066964, rs28674001), while con-
trol individuals (three healthy and two psoriatic volunteers)
carried the wild-type alleles. Of the 15 patients with sporadic
PRP, eight carried SNVs. In all of them only two types of
polymorphisms were detected either alone or in combination
(rs2066964 and rs28674001). Additionally, in three patients
we detected mutations in the CARD14 gene (rs2289541,
rs34367357, c.1198_1199CG/TA). Further in vitro and in situ
functional studies were carried out in the patient with familial
PRP to examine the functional relevance of the genetic vari-
ants. Immunofluorescent staining revealed nuclear localization
of the nuclear factor (NF)-jB p65 subunit in the PRP skin
specimen, indicating activated NF-jB, in contrast to healthy
and psoriatic skin sections where only cytoplasmic staining of
inactivated NF-jB was shown. An NF-jB luciferase reporter
assay demonstrated significantly increased NF-jB activity in
keratinocytes from the patient with PRP compared with
healthy keratinocytes. Characterization of the cytokine profile
of the keratinocytes and peripheral blood mononuclear cells
demonstrated that the higher NF-jB activation in PRP cells
induced higher responses to inflammatory stimuli compared
with healthy cells. Our study indicates the importance of
CARD14 in patients with PRP and highlights that functional
characterization of rare and common variants of the CARD14
gene can bring us closer to understanding the role of genetic
variants in disease pathogenesis. Funding: K111885, GINOP-
2.3.2-15-2016–00015 and GINOP-2.2.1-15-2016-00007
P116Early changes in peripheral leucocyte populationsduring oral dimethylfumarate treatmentP. Morrison, D. St€olzl, S. Kurras, S. Gerdes andU. MrowietzUniversit€atsklinikum Schleswig-Holstein, Kiel, GermanyDimethylfumarate (DMF) is a common first-line drug used for
the treatment of moderate-to-severe psoriasis. The immuno-
suppressive effect of DMF is associated with a reduction in the
peripheral blood lymphocyte count, which, when uncon-
trolled, can result in severe lymphopenia. However, early
changes in the leucocyte compartment are relatively unre-
ported. Thus, in the current study we have assessed the
changes in blood leucocytes in a cohort of patients with psori-
asis during the first 3 months of DMF treatment. Using multi-
colour flow cytometry we assessed the frequencies of CD4 and
CD8 T cells and neutrophils. Our results showed that the
majority of DMF-treated patients had a reduction in absolute
leucocytes after only 1 month of treatment. When analysed in
detail we found that a loss of peripheral neutrophils was pri-
marily responsible for this reduction, particularly in the first
month of treatment. In most patients, the reduction in neu-
trophils persisted at all time points. - cell counts were gener-
ally increased compared with baseline after 1 month of
treatment. Hence, the number of peripheral CD3+ T cells was
increased in 69% of patients with a mean increase to
158.3 � 36.7% of the pretreatment baseline. Increases in both
CD4 and CD8 T cells accounted for this change. At the same
time point, a drop in the number of T cells was seen in 23%
of patients, with a mean decrease to 57.7 � 17.1% of the
pretreatment value. Both CD4 and CD8 T cells were reduced.
The losses in peripheral T-cell number were more prevalent
by month 3, when 61.5% of patients had a reduced CD3
T-cell count, with a mean decrease to 55.6 � 13.6% of base-
line. Again, both CD4 and CD8 T cells were affected, with
CD4 T cells at 56.5 � 14% compared with baseline and CD8
T cells at 52.7 � 19.7%. However, no patients were consid-
ered lymphopenic by month 3, as all had a CD3 count
> 0.5 9 109 cells L�1. The remaining 38.5% of patients dis-
played a mean relative increase in CD3 T-cell count to 132.7%
of baseline, with both CD4 and CD8 cells increased. Our data
show that neutrophils are affected by oral DMF from an early
time point, while it takes longer for T cells to be reduced. As
neutrophils are critical for psoriasis pathogenesis, it is likely
that these changes are linked to the disease ameliorating effect
of DMF.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 69
P117Randomized controlled trial of patient-initiatedcare for patients with psoriasisL. Khoury,1 T. Møller,2 C. Zachariae1 and L. Skov11Department of Dermatology and Allergy, Herlev and Gentofte Hospital,
University of Copenhagen, Copenhagen, Denmark and 2University Hospitals
Centre for Health Care Research, Rigshospitalet, University of Copenhagen,
Copenhagen, DenmarkTreatment and care of moderate-to-severe psoriasis often
require lifetime consultations by dermatologists with close
monitoring of systematic treatment. Moreover, psoriasis is a
fluctuating disease and the patient’s healthcare needs depend
on the current severity of their psoriasis, indicating that
healthcare services plays a more significant role during some
periods of patients’ lives. We hypothesize that a more flexible
system may reduce inappropriate follow-up consultations,
release resources to difficult consultations, and improve patient
quality of life and satisfaction with healthcare. We therefore,
aimed to determine the effect of patient-initiated care (PIC)
for patients with psoriasis in a dermatology outpatient clinic.
A prospective randomized controlled trial was set up. Patients
on well-controlled systemic treatment were randomly assigned
to either (i) the PIC group, where patients received one yearly
scheduled consultation with a dermatologist and with no rou-
tine follow-up consultations, but patients were able to initiate
consultations when needed or (ii) the control group, where
patients received consultation routinely every 12–16 weeks.
The main outcome was Dermatology Life Quality Index
(DLQI), and secondary outcomes were clinical status, safety
and patient satisfaction with healthcare assessed at baseline
and after 1 year. In total 150 patients were included in the
study (73 in the PIC group and 77 in the control group).
Overall 58.0% were treated with biologics, 37.3% with
methotrexate and 4.7% with acitretin. Patients in the PIC
group requested a mean � SE of 2.46 � 0.13 consultations
vs. 5.05 � 0.61 in the control group, corresponding to
64.2% fewer appointments for the PIC group over 1 year
(P = 0.001). Having fewer consultations did not decrease
safety for patients in the PIC group, and no statistical signifi-
cantly mean difference was detected for Psoriasis Area and
Severity Index, 0.08 � 0.23 vs. �0.16 � 0.2 (P = 0.42), or
laboratory control, 0.21 � 0.67 vs. 0.21 � 0.47 (P = 0.093)
in the PIC and control groups, respectively. Patients reported
high satisfaction with healthcare, and no significant mean dif-
ferences were observed between groups regarding satisfaction
with overall care (P = 0.24), treatment (P = 0.75) and infor-
mation (P = 0.09). There was also no change in DLQI:
0 � 0.22 vs. 0.28 � 0.23 (P = 0.38). PIC offers some clinical
benefits compared with routine care, giving patients more
flexibility and less dependence on doctors and clinical visits.
The intervention adds no harm to monitoring systematic pso-
riasis treatment, and patients report high quality of life and
satisfaction with healthcare. Avoiding unnecessary consulta-
tions releases resources to organize a more patient-centred
approach to dermatology services, providing time to support
patients during vulnerable periods and psoriasis relapse, and
decrease comorbidity risk. This study has been registered with
Clinicaltrials.gov, file no. NCT02382081.
P118Establishment of an intradermal ear injectionmodel of interleukin (IL)-17A and IL-36c as a toolto investigate the psoriatic cytokineD. Kluwig, S. Huth, C. Pfaff, L. Huth, Y. Marquardt,K. Fietkau, J.M. Baron and B. L€uscherUniklinik RWTH Aachen, Aachen, GermanyPsoriasis is a chronic skin disease caused by the excessive
secretion of inflammatory cytokines, and affects 2–3% of the
Western population. The proinflammatory interleukin (IL)-
17A is a key cytokine in psoriasis. However, accumulating evi-
dence has revealed that IL-36c also plays a pathogenic role in
this disease. So far, using keratinocyte monolayers and a
three-dimensional psoriasis model we have already detected a
feedback loop between the IL-17 and IL-36 cytokines that
induces and maintains psoriasis pathology. To understand
more precisely the role of the IL-17A–IL-36c cytokine net-
work in skin pathology, we used an ear injection model in
our present study. Therefore, we injected IL-36c and IL-17A
alone or in combination into the ear pinnae of mice. After
4 days of consecutive treatment mice were euthanized and
histological and immunohistological stainings were performed.
The intradermal delivery of IL-17A and IL-36c resulted in a
significant increase of the ear thickness measured over time.
Histological evaluation of IL-17A- and IL-36c-treated skin
showed a strong acanthosis accompanied by hyperkeratosis
and spongiosis. We found the same histological features in
mice that underwent injections with IL-36c alone, but to a
lesser extent. IL-17A on its own was not able to induce psori-
asis-like changes in the mouse skin. Moreover, the expression
of genes encoding antimicrobial peptides, like mS100A8,
mDEFB4 (orthologue of human b-defensin 2), mS100A7A
and mDEFB14 (orthologue of human b-defensin 3) were
upregulated after treatment with IL-17A and IL-36c in combi-
nation. Similar effects were partially seen after the injection of
IL-17A and IL-36c alone, but the expression was much
weaker. In conclusion, intradermal injection of IL-17A and
IL-36c in the ear pinnae of mice provides an in vivo model to
investigate psoriasis. Our results strengthen the thesis that
IL-17A and IL-36c drive psoriatic inflammation via a synergis-
tic interaction. Our established intradermal ear injection model
of IL-17A and IL-36c can be utilized in future to monitor
effects of various inhibitors of this cytokine network.
P119Pharmacogenomic signature of response togenistein therapy for psoriasis: effects of genisteinin vitro and in vivo and its mechanism of actionE. Smoli�nska,1 M. Moskot,1,2 K. Boche�nska,1
A. Lewczuk,3 T. Brodniewicz,3 J. Jak�obkiewicz-Banecka1 and M. Gabig-Cimi�nska1,21Department of Medical Biology and Genetics, University of Gda�nsk, Gda�nsk,
Poland; 2Institute of Biochemistry and Biophysics, Polish Academy of
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
70 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
129ABSTRACTS
Sciences, Laboratory of Molecular Biology (affiliated with the University of
Gda�nsk), Gda�nsk, Poland and 3MTZ Clinical Research Sp. z o.o., Warsaw,
PolandPharmacogenomics has the potential to facilitate the develop-
ment of safer and more effective drugs in terms of their benefit
and/or risk profiles. Genistein, a soy-derived isoflavone, has
attracted attention as a potent agent in the treatment of psoriasis.
It is also known as an agent modulating expression of various
genes. The aim of the current study was to perform the first
pharmacogenomic study on genistein treatment in an in vitro
model of human keratinocyte culture, and also in patients with
psoriasis in the Polish population (lesional and nonlesional skin,
and blood) using mRNA expression profiling of genetic markers
to assess prediction of response to drug therapy. For the in vitro
study, the cytotoxic and antiproliferative activities of genistein
against keratinocytes were tested. The effect of the anti-inflam-
matory and antipsoriatic activity of genistein on gene expression
was investigated by culturing human epidermal keratinocytes
under inflammation-inducing conditions. The involved sig-
nalling pathways were studied by treating the cells with specific
inhibitors. Global gene expression profiling was performed, fol-
lowed by dedicated real-time quantitative reverse-transcriptase
polymerase chain reaction (qRT-PCR) custom panel analyses for
identification of activity of genistein-responsive genes. Assess-
ments were made of phosphoinositide 3-kinase activity, nuclear
factor-jB translocation, activation of reactive oxygen species,
and inflammatory cytokine levels following genistein treatment.
For the in vivo study, participants underwent detailed phenotyp-
ing and were assessed about their response to therapy using the
Psoriasis Area and Severity Index, body surface area involvement
and Physician’s Global Assessment. Skin biopsy and blood sam-
ples were collected at two time points: at baseline and after
56 days of therapy. Dedicated real-time qRT-PCR custom panel
analyses for identification of activity of genistein-responsive
genes were performed on RNA extracted from lesional and non-
lesional skin, and blood samples (n = 4). Efficacy studies of
genistein action were made via determination of interleukin
(IL)-12, IL-17, IL-23 and tumour necrosis factor-a levels. Test-
ing the effects of genistein on the human cell transcriptome, we
found that this compound significantly modulated activities of
psoriasis-like transcripts, by reducing the expression efficiency
of genes revealing enhanced activity in psoriatic cells, and by
stimulating the expression efficiency of genes revealing
decreased activity in psoriatic cells. Treatment with genistein
was safe and well tolerated with no significant changes. A psori-
asis screening qRT-PCR array has been developed for monitor-
ing of patients with psoriasis undergoing isoflavone therapy.
P120Itch and pain perception and epidemiology inpatients with psoriasis: results from a prospectivetwo-centre studyN. Max,1 K. Torz,1 U. Mrowietz,1 V. Oji,2 S. St€ander3
and S. Gerdes1
1Psoriasis-Center, Department of Dermatology, University Medical Center
Schleswig-Holstein, Campus Kiel, Kiel, Germany; 2Department of
Dermatology, University Hospital M€unster, M€unster, Germany and 3Center
for Chronic Pruritus, Department of Dermatology, University Hospital
M€unster, M€unster, GermanyTo treat psoriasis it is necessary to achieve a therapeutic alliance
with the patients. Thus, patient-related aspects should be taken
into account. A crucial and life-quality-reducing symptom of
psoriasis is pruritus, and recent studies show that itching is the
predominant symptom in the patient’s awareness of disease.
Clinical comparison with other dermatoses suggests differences
in the characteristics of pruritus, for example as patients with
psoriasis rarely present skin artefacts due to scratching. Specific
investigations on different skin symptoms and the frequency,
location and onset of pruritus are missing. In order to improve
patient management, we have characterized the clinical aspects
of pruritus at two specialized psoriasis centres in Germany. In
total 282 were been included in this prospective study. During a
face-to-face interview, both a self-developed and multiple speci-
fic itch questionnaires (including ItchyQoL) were used to assess
the perception and epidemiological data of pruritus within this
patient cohort. The mean age was 49.5 � 14.9 years and the
mean Psoriasis Area and Severity Index was 5.21 � 6.92,
reflecting that patients were moderately affected by psoriasis.
Pruritic symptoms were reported by 59.9% of all patients. In
total 37.2% of the patients reported that the onset of any pruritic
symptoms was either coincident with or after psoriasis onset.
Overall 60.3% of the patients were able to localize their itch.
Three-quarters (73.5%) of these patients felt symptoms only
within psoriatic lesions, whereas only 12.4% of the patients also
experienced perilesional itch. Another 12.4% of the patients
reported itch all over their body, while only 1.7% of the patients
had itch in unaffected skin only. Of all patients who reported on
itch frequency (n = 170), 63.5% had symptoms during five or
more days a week. Only 22.9% of the patients had symptoms
on less than 3 days per week. Out of 170 patients, 54.7% had
skin pain instead of itch and 79 patients stated that they were
able to differentiate clearly between itch and skin pain symp-
toms. In total 60.8% of 176 patients reported on an impact on
interpersonal relationships and 64.8% have had sleep distur-
bances. In conclusion, this study underlines the high frequency
and importance of pruritic symptoms in patients with psoriasis
and reveals a strong relationship with psoriatic lesions. The
symptom of skin pain could be distinguished from itch by
almost half of the patients, supporting the idea of a specific pso-
riasis itch that should be investigated in more detail.
P121Body locations of difficult-to-treat psoriasis in theera of treatment with biological agents: a Danishmulticentre studyK.F. Hjuler,1 L. Iversen,1 K. Kofoed,2 M. Rasmussen,1
L. Skov2 and C. Zachariae21Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
and 2Department of Dermato-Allergology Gentofte Hospital, University of
Copenhagen, Copenhagen, DenmarkTraditionally, psoriasis in certain body sites has been acknowl-
edged as difficult-to-treat variants. Such locations are the scalp,
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 71
nails, palms, soles and intertriginous areas. During the last
decade, several highly effective systemic agents have been
approved for the treatment of psoriasis. Despite the availability
of these novel agents, the same areas are still considered diffi-
cult to treat. To our knowledge, no published studies have
examined the location of recalcitrant psoriasis in patients trea-
ted with biological agents. The aim of this study was to inves-
tigate the location of treatment-refractory psoriasis in patients
treated with biological agents in real-world clinical practice. In
this observational study we investigated the skin and/or nail
location of treatment-refractory psoriasis in patients with
moderate-to-severe psoriasis treated for > 6 months with bio-
logical agents approved for the treatment of psoriasis with a
partial or good response to treatment and a Psoriasis Area and
Severity Index (PASI) 1–5. Experienced PASI assessors in two
university hospital dermatology clinics included patients con-
secutively in the database. Both sites used a uniform data col-
lection method predefined in a data entry form in which the
body area was divided into 26 regions and 20 nails. Between
May 2017 and August 2017 we included 111 patients with
chronic plaque-type psoriasis: 75.0% men, mean age
50.7 � 13.3 years, with a median PASI score of 2.4,
interquartile range (IQR) 1.2–3.4. The most commonly used
biological agent was ustekinumab (35.1%). The median dura-
tion of treatment with biologics was 48 months (IQR 12–84).The median PASI reduction from treatment initiation was
86.1% (IQR 78.4–91.7). The most common site of recalcitrant
psoriasis in this cohort of patients treated with biological
agents was the anterior lower leg region [49.5%, 95% confi-
dence interval (CI) 40.2–58.9]. Further common sites of
recalcitrant psoriasis were the posterior lower leg region
(22.5%, 95% CI 14.8–30.3), the elbow region (36.0%, 95%
CI 27.1–45.0) and the scalp (18.9%, 95% CI 11.6–26.2).Regarding the body regions traditionally considered as diffi-
cult-to-treat sites the proportions of patients with recalcitrant
psoriasis were fingernails 11.7% (95% CI, 5.7–17.7), toenails12.5% (95% CI 6.1–18.9), scalp 18.9% (95% CI 11.6–26.2),palmar region 3.6% (95% CI 0.1–7.1), plantar region 0.9%
(95% CI �0.9 to 2.7) and intertriginous areas 9.0% (95% CI
3.7–14.3). In conclusion, in real-world clinical practice, the
most common sites of recalcitrant psoriasis in patients treated
with biological agents are the anterior crural region, the pos-
terior crural region and the elbows. The regions traditionally
accepted as difficult-to-treat areas were rarely affected with
recalcitrant lesions, although the scalp was often not clear.
P122The effect of monomethylfumarate on human bloodneutrophilsI. Suhrkamp, A.-S. Erkens, P. Morrison andU. MrowietzPsoriasis-Center Kiel, Department of Dermatology, University Medical Center
Schleswig-Holstein, Campus Kiel, Kiel, GermanyFumaderm, a mixture of fumaric acid esters, has been used to
treat psoriasis for more than 20 years. It was shown that
monomethylfumarate (MMF), the active metabolite of
Fumaderm’s main component, dimethylfumarate, binds to
hydroxycarboxylic acid receptor 2 (HCA2). As neutrophils
play a major role in the pathogenesis of psoriasis, we investi-
gated the effects of MMF on human neutrophils. By flow
cytometry we studied neutrophil counts in the blood of
patients with psoriasis taking Fumaderm. Most patients
showed a drop in neutrophil count in the first 3 months after
starting treatment. We assessed HCA2 expression by human
blood leucocytes and found that in contrast to T cells, B cells
and eosinophils, neutrophils expressed HCA2 protein on their
surface. In vitro stimulation of neutrophils revealed that HCAR2
mRNA expression could be upregulated by interferon-c. TheHCA2 receptor agonists MMF and nicotinic acid did not
change HCA2 transcript levels. In contrast, nicotinic acid and
MMF were able to reduce HCA2 surface protein levels when
analysed by flow cytometry, indicating that MMF can cause
agonist-induced internalization of HCA2. To determine
whether the neutrophil drop seen during fumarate treatment
was due to the induction of apoptosis, we stimulated human
neutrophils with MMF in vitro and assessed the rate of apopto-
sis using annexin V staining. We found that MMF did not
increase the rate of apoptosis in neutrophils when compared
with vehicle-stimulated samples. Using a Proteome Profiler
Array we assessed whether MMF could induce any apoptosis-
related signalling pathways in neutrophils. In agreement with
our annexin V results we found that MMF did not induce
phosphorylation of any apoptosis related-proteins. HCA2 ago-
nists have been reported to inhibit the forskolin-induced accu-
mulation of intracellular cAMP. Thus we investigated whether
MMF could have a similar effect; however, we found that
MMF caused a small nonsignificant decrease in cAMP in for-
skolin-activated neutrophils. We determined that MMF was
unable to induce a calcium flux in neutrophils. These data
indicate that the drop in blood neutrophils observed in Fuma-
derm-treated patients with psoriasis is not due to direct induc-
tion of neutrophil apoptosis. Therefore, other indirect
mechanisms that alter the size of the blood neutrophil
population must exist. The internalization of HCA2 in
response to MMF by neutrophils indicates that there are
downstream signalling events occurring, but that these do not
appear to be linked with changes in the second messengers
cAMP and calcium.
P123Psychological distress in patients using systemictherapies for psoriasis: the role of beliefs aboutillness and anger suppressionR. Thorneloe, C.E.M. Griffiths, R. Emsley, D. Ashcroft,L. Cordingley and on behalf of the PSORT studygroup and BADBIRUniversity of Manchester and Manchester Academic Health Science Centre,
Manchester, U.K.High levels of psychological distress can influence long-term
outcomes for people with psoriasis via psychophysiological
and behavioural pathways such as alcohol use or nonadher-
ence to medication. Beliefs about illness affect how people
© 2017 British Association of DermatologistsBritish Journal of Dermatology (2017)
72 Psoriasis Gene to Clinic
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
131ABSTRACTS
cope and adjust to psoriasis, but few studies have explored
these relationships in those using biological therapies. We
assessed levels of general and psoriasis-specific psychological
distress and levels of anger experience in patients using con-
ventional systemic and biological therapies. We evaluated fac-
tors associated with distress using regression analyses. Cross-
sectional data from 811 patients using conventional systemic
and biological therapies for the treatment of moderate-to-
severe psoriasis and enrolled in the British Association of Der-
matologists Biologic Interventions Register (BADBIR) were
collected from 35 dermatology centres across England. We
measured anger expression (State-Trait Anger Expression
Inventory), distress (Hospital Anxiety and Depression Scale;
HADS), beliefs about psoriasis (Revised Illness Perception
Questionnaire) and medication (Beliefs about Medicines Ques-
tionnaire). A score ≥ 8 on the HADS indicates a possible or
probable caseness of anxiety and/or depression. High propor-
tions of the sample were classified as possible or probable
caseness for anxiety (40%) and/or depression (24%), with
two-thirds reporting strong negative psoriasis-specific distress
and almost half (47%) reporting strong feelings of anger
towards their psoriasis. In total, 11.5% reported a high level
of anger suppression. Stronger suppression of anger was asso-
ciated with anxiety (standardized b = 0.40, P ≤ 0.001),
depression (b = 0.40, P ≤ 0.001) and negative psoriasis-speci-
fic distress (b = 0.11, P = 0.001). Holding strong beliefs that
psoriasis has negative consequences was associated with nega-
tive psoriasis-specific distress (b = 0.49, P ≤ 0.001). There
were different drivers of anxiety and depression with worries
about appearance associated with anxiety (b = 0.13,
P = 0.006), whereas concerns that psoriasis is noticeable to
others was associated with depression (b = 0.17, P ≤ 0.001).
Patients who expressed the strongest medication concerns
were more likely to report higher depression scores
(b = 0.10, P = 0.002). Psychological distress remains high for
many patients using systemic therapies. Some patients using
biologics may require additional interventions to target long-
held beliefs and address emotion-focused coping strategies in
order to improve clinical outcomes and quality of life.
C.E.M.G. is a National Institute for Health Research Senior
Investigator. PSORT is funded by the Medical Research Coun-
cil, grant MR/1011808/1.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017)
Psoriasis Gene to Clinic 73
NOTES
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
133
Author Index
© 2017 The AuthorsBJD © 2017 British Association of Dermatologists British Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4 1
van Aarle, F., P004 Abe, N., P096 Abram, K., P097 Agada, N., P014 Ahn, R., P038 Ainscough, J., P009 Alase, A., P009 Alashqar, M., P010 Alikhan, M., P016 Anandan, A., P019 Andersen, A.-M.N., P100 Antoniou, C., P055 Arakawa, A., FC05, FC17, P066 Arakawa, Y., FC05 Arenberger, P., P021 Arendt, C., FC32 Armstrong, A., P003 , P103 Ashcroft, D., P078, P086, P101, P123 Asmawidjaja, P., FC27, P063, P064, P065 Augustin, M., FC21, FC26, FC30, P021, P044,
P104
Bachelez, H., FC20, P032 Baeten, D., P065 Bagel, J., FC29 Baker, C., P020 Banecka, J.J., P023 Bangert, C., FC33 Barbarot, S., P032 Barker, J., FC23, FC24, P002 , P052 Baron, J., P049 , P118 Barron, M.J., P084 Barry, J., FC22 Baskan, E.B., P041, P042 Bassukas, I., P055 Bata-Csörgo, Z., FC24, P114, P115 Bayaraa, B., P082 Beamer, M., FC25 Belkhodja, C., FC18 Beneton, N., P032 Benezeder, T.H., P079 Berends, M., P083 Berggren, L., P092 Bertelsen, T., P048 Besgen, P., P066 Bewley, A., P003 Beylot-Barry, M., P032 Bianchi, L., P040 Bisoendial, R., FC27, P064, P065 Bissonnette, R., FC31, P085 Blauvelt, A., FC29, FC32, P004, P022, P105 Blegvad, C., P100 Bochenska, K., P023, P119 Boehncke, W.-H., P003 van den Bogaard, E., FC04 Bomas, S., P017 Boon, L., P063 Bøttcher, M., P102 Boutouyrie, P., FC20 Bouwstra, J., FC04 Branigan, P.J., P106
de la Brassinne, M., P070 den Braanker, H., P064 Bravard, P., P032 Bridgewood, C., P089 Brodmerkel, C., FC08 Brodniewicz, T., P119 Broesby-Olsen, S., P075 Brooke, M., FC14 Brown, G., P009 Bryld, L.E., P075 Bukhalo, M., FC29 Bulfone-Paus, S., P084 Bundy, C., FC21 Bunton, D., FC22 Burden, D., FC23, FC24 , P052 Burge, D., FC32 Burkhardt, N., P092
Cai, S., P072 Calimlim, B., P029 Callis Du ffi n, K., FC12 Camez, A., FC29 Campbell, K., FC08, P106 Capon, F., FC24, P002 Carr, M.J., P078 Catapano, M., P002 Chadoutaud, B., P087 Chakravadhanula, U., P061, P067, P090 Chandrashekar, B.S., P090 Chaparro, D., P081 Charifa, O.S., P037 Chasapi, V., P055 Chen, J.-Q., P072 Chen, M., P073 Chen, W., P025 Chen, X., P073 Chen, X.-B., P072 Chen, Y., P106 Cheuk, S., FC19 Cheung, S.T., P028, P028 Chijavadze, N., P107 Chikh, A., FC14 Choon, S.E., FC24 Chosidow, O., P032 Ciccarelli, F., P002 Classon, C., FC19 Connolly, A., P034 Conrad, C., FC18 Cordey, M., FC21 Cordingley, L., P101, P123 Correia, E., P024 Cortes, C., P081 Cueto, I., P013
D’Adamio, S., P040 Dam, T., P075 Dand, N., FC07 Danis, J., P114, P115 Davelaar, N., FC27, P064, P065 Davey, P., P020 Dekker, E., P003
Delaporte, E., P032 Demaria, O., FC03, FC18 Deng, J., P006 DePrimo, S., P106 DeShazo, R., P062 Dewey, F., FC12 Di Domizio, J., FC03, FC18 DiMeglio, P., P034 Dizman, D., P041, P042 Djamei, V., P044 Dodds, M., P073 Dossenbach, M., P094 Drew, J., FC32 Driessen, R., P083 Du, S., P088 Du ff us, K., FC15 Dupuy, A., P032 Duric, M., FC22 Dutronc, Y., P094 Dutz, J.P., P039
Ebongo, C., P076, P077 Eding, C.B., P098, P113 Egeberg, A., FC01, FC28, P074, P075 Eidsmo, L., FC19 Ejarque, R.A., FC09 Ekman, A.-K., P098, P113 Elder, J., FC04, FC16 , P038 Ellinghaus, D., P038 Emsley, R., P101, P123 Enerbäck, C., P098, P113 Enk, A., FC11 Erkens, A.-S., P122 Erkılıc, A.C., P041, P042 Ewald, D.A., P099 Eydieux, C., P087 Eyerich, K., FC21 Eyre, S., FC15
Fakharzadeh, S., P062 Fan, X., P111 Farkas, K., FC24, P115 Fathy, M., P060 Fazeli, A., P097 Fearnley, G., P089 Fei, C., P025 Feng, B.-J., FC12 Fernández-Peñas, P., P003, P092 Festini, T., P029 Fietkau, K., P049, P118 Finlay, A., FC23 Fitz, L., P088 Flack, M., FC29 Florencia, E., P063 Foerster, J., P038 Foley, P., P053 Foo, M., FC06 Fotiadou, C., P031 Franke, A., P038 Frankel, E.H., FC29 French, L., FC18
AUTHOR INDEX
2 Author Index
© 2017 The AuthorsBritish Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4 BJD © 2017 British Association of Dermatologists
Frey, S., FC10 Fries, A., FC03 Frueh, J., P021, P026 Fuentes-Duculan, J., P013 Furnholm, T., FC06
Gabig-Ciminska, M., P023, P119 Gál, B., P115 Galindo, C., P062 Galinski, A., FC05 Galluzzo, M., P040 Garcet, S., FC08, P013 Geng, Z., FC29 Georgakopoulos, J.R., P056, P057, P080,
P108, P109 Gerber, S.J., P073 Gerdes, S., FC10, P116, P120 Ghislain, P.-D., P070 Giboin, C., P032 Gilliet, M., FC03 , FC18 Gkogkolou, P., FC10 Gniadecki, R., P075 Göblös, A., P114, P115 Golbari, N., P091 Goldblum, O., P092 Goldgar, D., FC12 Goldstein, N., P010 Gong, Y., P025 Gonzaga-Jauregui, C., FC12 Gooderham, M., FC29, P104 Good fi eld, M., P009 Goodhead, C., P071 Gordon, W., P088 Gormsen, L.C., FC28 Gottlieb, A., FC32, P014, P026 Goyal, K., P062 Graham, A., P089 Gri ffi ths, C.E.M., FC21, FC23, FC24, P022,
P051, P052, P053, P078, P084, P086, P101, P105, P110, P123
Griewank, K.G., FC10 Grine, L., P059, P070 Groegel, K., P017 Grünthaler, V., P007 Gu, Y., FC29, P068 Gudjonsson, J., FC25 Guo, J.-Z., P027 Gürer, M.A., P041, P042 Guthery, S., FC12
Hü ff meier, U., FC10 Hambro, C., FC16 Hamdidouche, I., FC20 Hamdy, S., P060 Hammer, K., P079 Hampton, P., P052, P071 Han, L., P006 Hassam, B., P076, P077 Hatchard, C., FC23 Hawkes, J., FC12 Hazes, J., FC27, P064, P065 Helder, R., FC04 Helliwell, P., P009 Henderson, J., FC06 Hendriks, W., FC04 Henneges, C., P094 Heppt, F., P008 Hesselvig, J.H., P074
Hillary, T., P070 Hirano, H., P096 Hjuler, K.F., FC28, P102, P121 Hofman, A., FC27 Hollister, K., P094 Hu, Y., P073 Huang, Y., P006 Huneault, L., P003 Hunter, H.J., P051 Hussain, A., P011 Huth, L., P118 Huth, S., P118
Ighani, A., P056, P057, P058, P080, P108, P109
Ilona, S.E., P035 Imafuku, S., P082 Inzinger, M., FC33 Ioannides, D., P031, P055 Irvine, A., FC24 Iversen, L., FC28, P047, P048, P102, P121
Jabbar-Lopez, Z.K., P051 Jacobi, A., FC10 Jagun, O., P028, P028 Jakóbkiewicz-Banecka, J., P119 James, E., FC17 Janovák, L., P114 Jansen, P., FC04 Jaquet, J.-B., FC27 Jarvis, P., P024 Jarvis, S., P003 Jauslin, P., P011 Jazayeri, S., P021 Je ff ery, P., FC23 Jha, B.K., P061, P067 Jiang, G., P103 Johansen, C., P047, P048 Johnston, A., FC06, FC16 Joly, P., P032 de Jong, E., P083, P093 Joshi, S.D., P001 Jullien, D., P032
Kahlenberg, M., FC25 Kalia, S., P062 Kamstrup, M., FC01 Kaneko, S., P030 Kapur, N., P078 Karle, A., P024 Kawakami, H., P096 Keermann, M., P097 Kelsell, D., FC14 Kemény, L., P114, P115 Kerbusch, T., P004, P011 van de Kerkhof, P., P022, P083, P094 Keszegpal, A., P009, P089 Khettab, H., FC20 Khoury, L., P117 Kieras, E., P088 Kievit, W., P093 Kimball, A., P004, P091 , P103, P105 Kingo, K., FC10, P097 Kirby, B., P029, P051 Kirkham, B., P034 Kivelevitch, D., P018 Klekotka, P., FC31
Kleyn, E., FC21 , P051, P078 Klijn, S., P093 Kluwig, D., P049, P118 Kofoed, K., P074, P121 Kok, M.R., FC27 Kõks, S., FC10, P097 Kolbinger, F., P024 Kolios, A., FC22 van der Kolk, A., P093 Kölli, C., FC33 Körber, A., FC10, FC26 Korge, B., P017 Korom, I., P115 Koscielny, V., FC21 Kreppel, S., P051 van der Krieken, D., FC04 Krishnasamy, S., P062 Krueger, G., FC12 , P062 Krueger, J., FC08, P013, P088 Krupashankar, D.S., P090 Kubanov, A., P026 Kulkarni, P., P011 Kunder, G.G., P069 Kunjravia, N., P013 Kunze, A., FC11 Kurras, S., P116 Kusumawardani, A., P035
Lacombe, A., P085 Lacour, J.-P., FC29, P032 Lambert, J., P059, P070, P070 Lambert, S., FC16 Landeck, L., P072 Landén, N.X., FC19, P005 Lange-Asschenfeld, B., P079 Langhol ff , W., P055, P062 Langley, R., FC29, P062 Lapointe, A.-K., FC18 Lättekivi, F., P097 Latzko, A., P009 Laws, P., P009, P089 Lazaridou, E., P031 Lebwohl, M., FC32 Lee, J., P088 Leonardi, C., FC29, P022, P085 Leong, A., P036 Leslie, S., P038 Lewczuk, A., P119 Li, C., P050 Li, H., FC12 Li, J., FC31 Li, K., FC08 Li, Q., P004 Li, S., P054, P105 Li, W., P072 Li, X., P013 Liang, J., P050 Liang, Y., FC25 Liao, W., P038 Lichem, R., FC33 Limbu, L., P001 Liu, X., P106 Lockshin, B., P016 Lockwood, S., P091 Loft, N.D., P074 Löhr, S., FC10 Lovato, P., P099 Lu, C., P006
PSORIASISfrom gene to clinic
Email: [email protected]: www.psoriasisg2c.comPSORIASIS
from gene to clinic
135
Author Index 3
© 2017 The AuthorsBJD © 2017 British Association of Dermatologists British Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4
Luan, C., P073 Lubberts, E., FC27, P063, P064, P065 Luger, T., P085 van Lüimig, P., P083 Lunt, M., P051, P052, P086 Lüscher, B., P049, P118
Maa, J.-F., P029 McCarthy, S., FC12 McElhone, K., P051, P052 McGovern, A., FC15 Macleod, T., P009 Macluskie, G., FC22 Mahé, E., P032 Mahil, S., P034 Mai, S., P077 Maillère, B., P024 Mallbris, L., P014 Man, X.-Y., P072 Manasterski, M., P017 Manmath, P., P085 Manolson, M.F., P058 Mansouri, S., P076 Marini, J.C., P054 Marquardt, Y., P049, P118 Martin, P., FC15 Martini, E., FC19 Maruthappu, T., FC14, P034 Maryam, D., P037 Mashaly, H., P060 Mason, K.J., P051, P052 Matsumoto, Y., P096 Max, N., P120 Mayer, G., P079 Mazur, R., P085 Medeiros, A., P059 Mehta, N., P022 Meisgen, F., P005 Menter, A., FC31, P018 Mentz, H., P017 Mercieca, L., P110 Mesman, R., FC04 Meziane, M., P077 Milliken, M., FC12 Milutinovic, M., P022, P085 Min, M., P072 Mira, D.A., P035 Misery, L., P032 Mlynek, A., FC33 Modiano, P., P032 Møller, T., P117 Montgomery, D., P004 Morita, E., P030 Morrison, P., P116, P122 Moskot, M., P023, P119 Mössner, R., FC10 Motyer, A., P038 Mrowietz, U., FC26, P021, P116, P120, P122 Müllegger, R., FC33 Munoz, E.J., P106 Murphy, G., FC11 Murphy, R., P086 Mus, A.M.C., FC27 Mylonas, A., FC18
Nagy, N., P115 Nair, R., FC04, FC16 , P038
Navarini, A., FC18, P044 Niehues, H., FC04 Nielsen, J., FC28 Nielsen, T.E.T., P100 van Niftrik, L., FC04 Norsgaard, H., P099 Núnez Gómez, N., P017 Nylén, S., FC19
O’Connor, P., P039 O’Donnell, M., P003 Oehrl, S., FC11 Oguro, H., P030 Oji, V., FC10, P120 Oksenberg, J., P038 Okubo, Y., P096 Onsun, N., P041, P042 Oon, H.H., P033 Oortveld, M., FC04 Ormerod, A., P086 Osland, J.M., P073 Otten, M., P044 Otten-Mus, A.-M., P063, P064, P065 Ottosen, M.B., P075 Overton, J., FC12 Ozarmagan, G., P041, P042 Özcan, A., FC22 Ozkaya, D.B., P041, P042
Page, K., P088 Painsi, C., FC33, P079 Palmer, C., P038 Panicker, V.K., P019 Papanastasiou, P., P022 Papp, K., FC29, FC31, P014, P103, P104,
P105 Parasramani, S.G., P069 Parekh, M., P090 Pariser, D., FC29 Parisi, R., P078 Parneix, A., P021 Pascal, C., P085 Pasquali, L., P005 Pastorino, R., P040 Patel, D., FC31 Paul, C., P032, P094 Pawar, D., P090 Pawar, D.R., P069 Peeva, E., P088 Peña, L., P081 Peñaranda, E., P081 Peng, Q., P111 Peterson, L., FC32 Pfa ff , C., P049, P118 Philipp, S., FC10, FC29 Phung, M., P080, P108, P109 Pivarcsi, A., P005 Polzer, P., P104 Ponholzer, P., FC33 Ponnambalam, S., P089 Porter, M., P091 Prasada, R., P019 Praveen, K., FC12 Prens, E., FC27, P063 Price, L., P043, P045, P046 Prinz, J., FC05 Prinz, J.C., FC10, FC17, P066
Puig, L., P092
Quehenberger, F., FC33
Raap, J., P008 Rachida, &.S.-B., P037 Radhakrishnan, K., P019 Radiono, Suradi., P035 Radtke, M., FC21, FC26, FC30 , P044 Rahimi, R., P018 Rajagopalan, M., P003 Ralph, K., FC26 Randazzo, B., P054, P103 Rasmussen, M., P075, P121 Ratzinger, G., FC33 Ray-Jones, H., FC15 van den Reek, J., P083, P093 Reeves, E., FC17 Regnault, P., P021, P026 Régnier, S., P032 Reich, K., FC10, FC26, FC30, FC31, FC32,
P004, P017, P021, P022, P094, P103 Reid, D., P009 Reid, J., FC12 Reimann, E., P097 Rendon, A., FC11 Reynolds, N., P051, P086 Richard, M.-A., P032 Richter, L., FC33 Rigopoulos, D., P055 Riviere, J., P087 Roa, E., P081 Robinson, J., P043, P045, P046 Rodijk-Olthuis, D., FC04 Rolleri, R., FC32 Romiti, R., P003 Roussaki-Schulze, A., P055 Rundquist, I., P113 Rüter, P., P007 Ruzicka, T., P066
Sérézal, I.G., FC19 Salmhofer, W., FC33 Sarkar, M., FC25 Sator, P., FC33 Saxinger, W., FC33 Sayag, M., P087 Sbidian, E., P032 Schäkel, K., FC11 Schafer, P., P016 Schäkel, K., FC10 Schalkwijk, J., FC04 Schalkwijk, L., P083 Scherer, J., FC29 Schill, T., FC10 Schmidbauer, U., P079 Schmutz, J.-L., P032 Schork, N.J., P111 Schulz, P., FC10 Schütz-Bergmayr, M., FC33 Schwichtenberg, U., P017 Segaert, S., P070 Servín, O.R., P029 Seyger, M., P083 Shaker, O., P060 Shear, N.H., P056, P057 Shedden, K., FC06
AUTHOR INDEX
4 Author Index
© 2017 The AuthorsBritish Association of Dermatologists (2017) 177 (Suppl. S1), pp 1–4 BJD © 2017 British Association of Dermatologists
Shen, Y.-K., P053, P054, P103, P105 Shi, Y., P025 Singer, J.M., P013 Skak-Nielsen, T., P099 Skov, L., FC01, P074, P075, P100, P117, P121 Smith, C., FC24, P034, P052, P086 Smolinska, E., P023, P119 Sodha, M., P003 Soltani-Arabshahi, R., P062 Song, M., P053, P103 Sonkoly, E., P005 Sotiriou, E., P031 Souad, S., P037 Soura, E., P055 Spindeldreher, S., P024 Spuls, P., P059 Srivastava, A., P005 Srivastava, B., P062 Stacey, M., P009, P089 Ståhle, M., FC21, P005, P062 Ständer, H., FC10 Ständer, S., P120 Standish, K.A., P111 Steinz, K., FC10 Sticherling, M., FC10, P007, P008 Sticht, H., FC10 Stölzl, D., P116 Strober, B., P016 Strohal, R., FC33 Stuart, P., FC04 Suarez-Farinas, M., P088 Suhrkamp, I., P122 Sullivan, J., P020, P026 Summer, B., P066 Sun, L., P111 Suresh, S.H., P069 Swaroop, H.S., P090 Swindell, W., FC25 Széll, M., FC24, P114 , P115
Talamonti, M., P040 Tan, E., FC24 Tatarski, R., FC33 Tenon, M., P024 Thaçi, D., FC26, P085 Thomas, P., P066 Thompson, E.H.Z., FC29 Thorneloe, R., P101, P123 Thyssen, J., FC01 Tockova, O., P112
Tong, Y., P025 Torz, K., P120 Toth, D., P085 Trautinger, F., FC33 Tsagareishvili, K., P107 Tsai, T.-F., P022 Tsakok, T., FC02 Tsoi, L., FC04, FC25 , P038 Tsuboi, R., P096 Tubach, F., P032 Tuttle, J., FC31 Twelves, S., FC24 Tyring, S., FC29
Uebe, S., FC10
Van Gele, M., P059 Varga, E., P115 VataKuti, S., P011 Velangi, S., P036 Vendelbo, M.H., FC28 Verhaegh, D., FC27 Verma, D., P098 Verma, M., P036 Vernez, M., FC18 Viguier, M., FC20, P032 Virassamynaik, S., P087 Vis, M., P064, P065 van Vlijmen-Willems, I., FC04 Vollmer, S., FC05, FC17, P066 Voorhees, J., FC25 Vukcevic, D., P038 Vural, S., FC05
Wachter, E.A., P013 Wada, R., P011 Walsh, J., FC12 Walsh, S., P056, P057 Walton, S., P086 Wang, H., P111 Wang, P., P072 Wang, W.-H., P027 Wang, X., P025 Wang, Y., P025 Wang, Z., P068, P111 Ward, N., FC25 Warren, R.B., FC15, FC23, P003, P051, P052,
P086, P110 Was fi , Y., P053, P054, P103, P105 Webb, R.T., P078
Weger, W., FC33 Weimar, I., P047 Wenning, L., P011 Wenzel, J., P009 van de Wetering, G., P093 Willaert, F., P070 Williams, R., FC23 Wilsmann-Theis, D., FC10 Wilson, J., P020 Wimmer, J., P044 Winther, S., P102 Wittmann, M., P009, P089 Wolf, P., FC33, P079 Wu, J.J., FC29
Xi, L., P088 Xia, S., P085 Xiao, F., P111 Xing, X., FC25 Xu, H., P025 Xu, J., P095 Xu, W., P014 Xu, X., P063, P064, P065 Xu, Z., P068
Yan, K., P095 Yang, S., P111 Yeung, J., P056, P057, P080, P108, P109 Yin, X., P111 Yiu, Z., P052, P086 You, R., P021, P022, P026 You, Y., P053 Yu, Q., P025 Yuan, R., P073
Zachariae, C., FC01, P074, P100, P117, P121 Zeeuwen, P., FC04 Zhang, B., P088 Zhang, C.-L., P027 Zhang, L., P104 Zhang, W., P088 Zhang, X., FC13, P025, P050, P095, P111 Zheng, M., P072 Zheng, X., P111 Zhou, H., P054 Zhu, Y., P054 Zopf, Y., P007 Zorko, M.S., P112 Zuo, X., P111
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