2012 CME Annual meeting in multiple sclerosis “MS: from ... · 2012 annual continuing medical education (CME) accredited meeting: “MS: from disease management to patient management”

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2012 CME Annual meeting in multiple sclerosis

“MS: from disease managementto patient management”

Valencia, Spain18-19 May 2012

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All Serono Symposia International Foundation programmes are organized solely to promote the exchange and dissemination ofscientific and medical information. No forms of promotional activities are permitted. All Serono Symposia International Foundationprogrammes are made possible thanks to educational grants received from: Celgene, Centre d’Esclerosi Multiple de Catalunya,ComtecMed, Congrex Sweden, Congrex Switzerland, Cryo-Save, Datanalysis, Esaote, European Society of Endocrinology,Fondazione Humanitas, Fundación IVI, ISFP International Society for Fertility Preservation, ISMH International Society of Men’sHealth, K.I.T.E., Merck Serono, Sanofi-Aventis, University of Catania, Vall d'Hebron University Hospital.

Dear Colleague

On behalf of the Serono Symposia International Foundation we are delighted to welcome you to the2012 annual continuing medical education (CME) accredited meeting: “MS: from diseasemanagement to patient management”. At this meeting, leading international experts will cometogether to discuss current and future approaches to the treatment of multiple sclerosis (MS). Youwill also have the opportunity to earn CME credits.

This interactive meeting is divided into four sessions. Session 1 will cover the pharmacologicaltargets of current and possible future therapies, and the requirement for close safety monitoring ofnewer therapies. In session 2 we will detail how the neurologist can best use the tools available foroptimal diagnosis of MS and prediction of disease course. Session 3 will focus on current and futuretechniques to predict and monitor response to treatment, and in session 4 we will discuss the clinicalmanagement of MS, the relationship with the patient and how this can affect treatment adherence.Case studies will be presented, offering you the opportunity to discuss various aspects of clinicalpractice with the panel of experts.

The aims of the 2012 annual conference are to provide an update on the latest understanding of MSpathophysiology and the mechanisms of action of current drugs, to discuss how best to diagnosepatients and then predict and monitor treatment response, and to provide guidance on how best toensure patients get optimal benefit from treatment.

We anticipate that this programme will provide valuable updates for the clinician, and will stimulateengaging and enlightened debate on many of the complex issues surrounding the management ofpatients with MS. We look forward to your active participation.

Yours sincerely,

David BatesNewcastle upon Tyne, UK

Xavier MontalbanBarcelona, Spain

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AIM OF THECONFERENCE

Research into the pathophysiology of multiple sclerosis (MS)and the mechanism of action of new drugs has, in recentyears, produced a virtuous circle offering ever-new insights,enhancing our understanding of the disease and allowingoptimization of treatment. The 2012 Serono SymposiaInternational Foundation (SSIF) annual meeting will provide areview of these insights and offer the opportunity to discusshow to translate this increasing knowledge of managementimprovements for individual patients.

LEARNINGOBJECTIVES

By attending the conference, participants will:• be able to cite the latest research on MS pathophysiologyand modes of action of individual drugs

• be able to consistently apply standardized diagnostic criteriain daily practice

• improve their patients’ treatment adherence via improvedskills in sharing information

• be able to list present and future biomarkers of response totreatment.

ACCREDITATION Serono Symposia International Foundation(www.seronosymposia.org) is accredited by the EuropeanAccreditation Council for Continuing Medical Education(EACCME®) to provide the following CME activity for medicalspecialists. The EACCME is an institution of the European Unionof Medical Specialists (UEMS), www.uems.net

The 2012 CME annual meeting in multiple sclerosis: “MS: fromdisease management to patient management” to be held inValencia, Spain on 18-19 May 2012, is designated for a maximumof 9 (nine) hours of European CME credits (ECMEC). Eachmedical specialist should claim only those credits that he/sheactually spent in the educational activity. EACCME® credits arerecognized by the American Medical Association towards thePhysician's Recognition Award (PRA). To convert EACCME creditto AMA PRA category 1 credit, please contact the AMA.

TARGET AUDIENCE Clinicians involved in MS management.

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LEARNINGEFFECTIVENESS

PROJECT

The world of CME is changing with many different live andonline formats, and Serono Symposia InternationalFoundation (SSIF) is continually trying to improve its CMEactivities.

With your participation in a structured series of evaluations,SSIF can provide cutting-edge learning activities designed togive you the greatest value from the time you invest.

SSIF is running the learning effectiveness project for thismeeting.

During the conference you will be asked to answer somequestions to evaluate your knowledge and opinions on thespecific topics that will be covered in these two days.

We also kindly ask you to assess the program in variousdomains such as whether you were satisfied with the meeting,whether it met the stated learning objectives, whether thecontents were neutral and will be applicable to your dailypractice.

After the event, you will be involved in two additional steps:• Post-event: three weeks after the event we will email you ashort questionnaire which will give you the opportunity totell us how much of what you learned has had an affect onyour know-how and daily practice.

• Follow-up: three-months after the event, we will contact youwith the final questionnaire.

We will collate and analyse your responses and use theresults to improve and develop our ongoing programs.

Of course, we commit to maintaining the confidentiality of theinformation you provide and we will inform you about theresults of the process regarding the activity that you attended.

Thank you very much for participating in this project!

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LANGUAGE The official language of the conference will be English.

VENUE Meliá Valencia Palacio de CongresosAvenida Cortes Valencianas 52Valencia, Spain

CHAIRS David BatesDepartment of NeurologyRoyal Victoria InfirmaryNewcastle upon Tyne, UK

Xavier MontalbanMultiple Sclerosis Centre of CataloniaUnit of Clinical NeuroimmunologyVall d’Hebron University HospitalBarcelona, Spain

SCIENTIFICSECRETARIAT

Serono Symposia International FoundationSalita San Nicola da Tolentino, 1/B00187 - Rome, ItalyNeurology Team Leader: Serena Dell’AricciaAssociate Project Manager: Alessia AddessiPhone: +39 (0)6 420 413 251/591Fax: +39 (0)6 420 413 [email protected]

ORGANIZINGSECRETARIAT

Meridiano Congress InternationalVia Mentana, 2/B00185 - Rome, ItalyCongress Coordinator: Debora UrbinelliPhone: +39 (0)6 88 595 [email protected]

Scientificprogramme

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Pharmacological targets and evolvingpathophysiological conceptsD. Bates (UK)

09.00 L1 Improving understanding of mechanism of action ofimmunomodulatory drugsB. Kieseier (Germany)

09.30 L2 Neuroprotection and steps towards neuroregeneration:promising therapeutic targetsR. Gold (Germany)

10.00 L3 Resetting the immune system: stem cell transplantationA. Uccelli (Italy)

10.30 L4 Efficacy profiles of MS drugsG. Comi (Italy)

11.00 L5 Monitoring drug safety in clinical practiceP. Vermersch (France)

11.30 L5 Coffee break

Day 1Friday

18 May 2012

08.30SSIF OpeningG. Comi (Italy)

08.40Local welcomeB. Casanova (Spain)

08.50Welcome and introductionD. Bates (UK) and X. Montalban (Spain)

SESSION I

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MS Diagnosis and prognosisX. Montalban (Spain)

12.00 L6 McDonald criteria 2010: making the diagnosis easierA.J. Thompson (UK)

12.30 L7 The diagnosis of MS before MSM. Tintorè (Spain)

13.00 L8 What can magnetic resonance imaging tell us about diseaseevolution in the individual patient?D. Arnold (Canada)

13.30 L5 Lunch

14.30 C1 Case study: Differential diagnosis - neuromyelitis optica vs MSPresenter: P. Rieckmann (Germany)Discussant: L. Moiola (Italy)

SESSION II

Treatment monitoringG. Comi (Italy)

15.10 L90 BiomarkersG. Giovannoni (UK)

15.40 L10 MRI as a potential marker of treatment response in currentclinical practiceA. Rovira (Spain)

16.10 L11 Present and future roles of pharmacogenomicsJ. Oksenberg (USA)


17.00 L12 Assessment of treatment responseM.S. Freedman (Canada)

17.30 C2.. Case study: Treatment and treatment algorithmsPresenter: G. Comi (Italy)Discussants: X. Montalban and O. Fernández (Spain)

18.10 L11 End of the day

SESSION III

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From disease management to patientmanagementB. Casanova (Spain)

09.00 L13 The patient’s willingness to take riskP. Rieckmann (Germany)

09.30 L14 How to implement the patient–caregiver partnership inclinical practiceD. Langdon (UK)

10.00 L15 Treatment adherence: how to measure it and how toimprove itJ. Sastre-Garriga (Spain)


10.50 C3.. Case study: Treatment failure due to lack of adherencePresenter: D. Langdon (UK)Discussants: P. Rieckmann (Germany) and

J. Sastre-Garriga (Spain)

11.30 C4.. Case study: Improved outcomes through tailored treatmentPresenter: D. Bates (UK)Discussants: G. Giovannoni (UK) and

P. Rieckmann (Germany)

12.10 L11 Concluding remarks

12.30 L11 End of the conference and closing lunch

Day 2Saturday

19 May 2012

SESSION IV

Douglas Arnold

David Bates

Bonaventura Casanova

Giancarlo Comi

Oscar Fernández

Mark S. Freedman

Gavin Giovannoni

Ralf Gold

Bernd C. Kieseier

Dawn Langdon

Lucia Moiola

Xavier Montalban

Jorge Oksenberg

Peter Rieckmann

Alex Rovira

Jaume Sastre-Garriga

Alan J. Thompson

Mar Tintorè

Antonio Uccelli

Patrick Vermersch

Faculty members

Biographies

David BatesChair / Chairman: Session I / Presenter: Session IV

Department of Neurology Royal Victoria Infirmary Newcastle upon Tyne, UK

David Bates trained in Medicine at Downing College, Cambridge and the Middlesex Hospital, London and in Neurology at theUniversity of Newcastle upon Tyne and the Mayo Clinic, Rochester, Minnesota, USA. He is Emeritus Professor of Clinical Neurologyat the University of Newcastle upon Tyne, Former Editor of the International MS Journal and past Chairman of both the MS Forumand the Medical Research Advisory Committee of the MS Society of Great Britain and Northern Ireland. He is Chairman of the JointColleges Working Party on the Vegetative State and Criteria for Brain Stem Death and Chairman of the Consensus Conference onthe Epilepsies for the Royal College of Physicians, Edinburgh. His research interests are in vascular disease, coma and theunconscious patient, and in MS. Professor Bates has published more than 150 peer-reviewed papers, edited three textbooks andcontributed chapters to more than 20. His current research involvement is predominantly in clinical trials of novel therapy in MS andin the role of mitochondria in protecting and repairing axons in the more chronic phases of that disease.

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Xavier MontalbanChair / Chairman: Session II / Discussant: Session III

Multiple Sclerosis Center of Catalonia Unit of Clinical Neuroimmunology Vall d’Hebron University Hospital, Barcelona, Spain

Xavier Montalban is Chair of the Department of Neurology-Neuroimmunology and Director of the Multiple Sclerosis Center ofCatalonia, Vall d´Hebron University Hospital, Barcelona, Spain and Professor of Neurology of the University Autònoma de Barcelona.Dr Montalban gained his MD in 1983 and was awarded a PhD in 1988, after formal training in neurology. In 1989 he undertook apostdoctoral research fellowship at Lupus Research Unit at St Thomas Hospital, London, UK, returning to Barcelona in 1990 tocreate the Unit of Clinical Neuroimmunology and research laboratory. Dr Montalban is a member of a number of scientificorganizations, Vice President of the Multiple Sclerosis Foundation, and sits on the advisory board and scientific committee of theMultiple Sclerosis International Federation, the European School of Neuroimmunology and the European Charcot Foundation. DrMontalban is the current Director for neuroimmunology contents of Revista de Neurología, a publication distributed to over 12,000professionals. He is also a member of several editorial boards of both national and international specialist journals. He haspublished over 250 original contributions in international journals and has authored a number of book chapters. Since 2003 he is amember of the advisory committee on clinical trials of new agents for the National Multiple Sclerosis Society, USA. Since 2009 heis a member of the executive committee of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).His current research interests include prognostic factor and biomarkers, immune mechanisms in MS, cognitive dysfunction in MS,new intervention strategies, genetic characterization and pharmacogenomics treatment response. He has participated in both thedesign and the execution of several Phase II/III clinical trials, and is a member of safety and steering committees.

Bonaventura CasanovaChairman: Session IV

Department of NeurologyUniversity Hospital La FeValencia, Spain

Bonaventura Casanova has been a specialist in Neurology at Hospital Universitari i Politècnic la Fe de Valencia, Spain, since 1991and is an Associate Professor of Neurology at the University of Valencia, Spain. Professor Casanova received his MD from theUniversity of Valencia in 1983. Following this, he continued his professional training at Servei Valencià de Salut in Valencia from 1988to 1991, and in 2001 received his PhD from the University of Valencia. He has authored more than 30 publications in neurology withinthe last 6 years and participated in six research projects as Principal Investigator and/or investigator collaborator. He has alsocontributed to more than 20 Phase II–IV clinical trials.

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Douglas ArnoldSpeaker: Session II

Montreal Neurological Institute and HospitalMontreal, Canada

Douglas Arnold is currently a Professor in the Department of Neurology and Neurosurgery at McGill University, Director of theMagnetic Resonance Spectroscopy Unit in the Brain Imaging Center at the Montreal Neurological Institute, and President ofNeuroRx Research, a CNS imaging CRO. He has special expertise in advanced magnetic resonance imaging (MRI) acquisition andanalysis techniques, particularly as they relate to understanding the evolution of MS and neurodegeneration. Dr Arnold combinesadvanced image processing of conventional structural images with non-conventional MRI acquisition techniques, such asmagnetization transfer imaging and magnetic resonance spectroscopy, to understand how inflammation in MS relates to injury tomyelin and neurons. He also uses these techniques to understand how new therapies for MS affect the pathobiology of the disease.Dr Arnold received his medical degree from Cornell University. He completed his residency in neurology at McGill University and apost-doctoral fellowship in magnetic resonance at the University of Oxford.

Biographies

Oscar FernándezDiscussant: Session III

Department of NeurologyHospital Regional Universitario Carlos HayaMalaga, Spain

Oscar Fernández is Head of the Department of Neurology, Hospital Regional Universitario Carlos Haya, Malaga, Spain, a position hehas held since 1991. In 2003, he was also appointed Head of the Institute of Clinical Neurosciences. Dr Fernández gained hislicensure in medicine and surgery from the Faculty of Medicine, Complutense University of Madrid, Spain. He completed hisresidency in neurology and internal medicine at the Hospital Clínico San Carlos in Madrid, before being awarded a PhD from theFaculty of Medicine of the University of Malaga in 1990. Subsequently, Dr Fernández was appointed Head Neurologist in theDepartment of Neurology at the Hospital Regional Universitario Carlos Haya. Malaga. He has been President of the Medical AdvisoryCommittee of the Fundación Española de Esclerosis Múltiple (FEDEM) since 1996, and was appointed President of the AndalusianNeurology Society in November 2007. Dr Fernández has authored over 200 published papers and book chapters, and serves as areviewer for several national and international neurological journals.

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Giancarlo ComiSSIF Scientific Committee President / Speaker: Session I / Chairman: Session III / Presenter: Session III

Department of NeurologyInstitute of Experimental NeurologyVita-Salute San Raffaele University, Milan, Italy

Giancarlo Comi received his degree in medicine in 1973 and neurological certification in 1977, both from the University of Milan, Italy.He joined the Department of Neurology, Scientific Institute San Raffaele, University of Milan, in 1974 as a Clinical Assistant and in1988 was appointed Assistant Professor in Clinical Neurophysiology. Currently he is Professor of Neurology, Chairman of theDepartment of Neurology, and Director of the Institute of Experimental Neurology at Vita-Salute San Raffaele University, ScientificInstitute San Raffaele, Milan. Professor Comi’s areas of interest are principally directed towards the study of the pathophysiology andtreatment of MS. He has authored and co-authored more than 800 articles in peer-reviewed journals and edited eight books. He hasa long-standing involvement as an active member of the steering committees and advisory boards of many international clinicaltrials, mainly in the field of MS. Professor Comi is the Vice President of the European Charcot Foundation and member of the Boardof Administration of the Italian Multiple Sclerosis Foundation and the Scientific Committee of the Italian Multiple SclerosisAssociation. Professor Comi has also served as President of the European Neurological Society and the Italian Society of ClinicalNeurophysiology. He is currently the President of the Italian Society of Neurology. Professor Comi currently sits on the executiveboards of various scientific associations and on the editorial boards of Clinical Neurophysiology, European Neurology and MultipleSclerosis and is the Associate Editor of Neurological Sciences.

Gavin GiovannoniSpeaker: Session III / Discussant: Session IV

Department of Neurology The Royal London Hospital Whitechapel, London, UK

Gavin Giovannoni was appointed to the Chair of Neurology, Blizard Institute of Cell and Molecular Science, Barts and The LondonSchool of Medicine and Dentistry, Queen Mary University of London and the Department of Neurology, Barts and The London NHSTrust in November 2006. In September 2008 he took over as the Neuroscience and Trauma Centre Lead in the Blizard Institute ofCell and Molecular Science. Professor Giovannoni did his undergraduate medical training at the University of the Witwatersrand,South Africa, where he graduated cum laude in 1987, winning the prizes for best graduate in medicine and surgery. He moved to theInstitute of Neurology, University College London, Queen Square, London in 1993, after completing his specialist training inneurology in South Africa. After 3 years as a clinical research fellow, under Professor Ed Thompson, and then 2 years as the ScarfeLecturer, working for Professor W. Ian McDonald, he was awarded a PhD in immunology from the University of London in 1998. Hewas appointed as a Clinical Senior Lecturer, Royal Free and University College Medical School, in 1998 and moved back to theInstitute of Neurology, Queen Square in 1999. He was promoted to Reader in Neuroimmunology in 2004. His clinical interests areMS and other inflammatory disorders of the CNS. He is particularly interested in clinical issues related to optimizing MS disease-modifying therapies. Professor Giovannoni’s current research is focused on Epstein–Barr virus as a possible cause of MS, definingthe “multiple sclerosis endophenotype”, MS-related neurodegeneration, biomarker discovery, clinical outcomes and immunetolerance strategies. His team focuses on translational research and therefore have an active clinical trial programme.

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Mark S. FreedmanSpeaker: Session III

Multiple Sclerosis Research UnitThe Ottawa HospitalOttawa, Canada

Mark S. Freedman is Professor of Medicine (Neurology) at the University of Ottawa and Director of the Multiple Sclerosis ResearchUnit at the Ottawa Hospital, General Campus. He received his medical degree from the University of Toronto and receivedpostgraduate neurology specialist training at Queen Square in London, UK, the University of Toronto, and the Montreal NeurologicalInstitute. Dr Freedman is a Fellow of the Royal College of Physicians and Surgeons of Canada (RCPSC), the American Academy ofNeurology (FAAN), and the College of Specialists of Quebec (CSPQ). For more than 25 years, Dr Freedman has been devoted totranslational research, with the main goals of understanding the immunopathogenesis of, and developing successful treatments for,MS. He has been the principal investigator on numerous clinical trials of new agents in MS, as well as been active on steeringcommittees that help design new clinical trials. Dr Freedman has published over 100 articles, book chapters and abstracts, and hasgiven hundreds of invited lectures and presentations, on both a national and an international level.

Biographies

Bernd C. KieseierSpeaker: Session I

Department of NeurologyHeinrich-Heine UniversityDüsseldorf, Germany

Bernd C. Kieseier received his undergraduate training at the Johannes-Gutenberg Univer-sity of Mainz, Germany and the MedicalSchool of West Virginia University, Morgantown, USA. After graduation as MD in 1994 he worked as an immunology fellow at the NewYork State Institute for Basic Research in New York, USA, followed by stays at the Lerner Re-search Institute, Cleveland Clinic, Ohio.He received training in Neurology at the Univer-sity of Würzburg, Germany and the University of Graz, Austria, where he becameProfessor of Neurology in 2001. Since December 2001 he is affiliated to the Department of Neurology at the Heinrich-Heine-University Düsseldorf, where he is Vice-Chair of the Department and Head of the MS Outpatient Clinic. His major clinical andresearch interests beyond general neurology are in the field of ex-perimental and clinical neuroimmunology with a focus on multiplesclerosis and immune-mediated neuropathies. He has authored or co-authored more than 200 articles in peer reviewed journals,written more than 40 book chapters and edited 3 books on neurology, neuroimmunology, peripheral nerve diseases and multiplesclerosis. Professor Kieseier participated in various clinical trials on MS as principle investigator, and is member of the medicaladvisory board of the German MS Society and member of the German Competence Network Multiple Sclerosis (KKNMS).

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Ralf GoldSpeaker: Session I

University of BochumBochum, Germany

Ralf Gold headed the Institute for Multiple Sclerosis Research, University of Goettingen and Gemeinnützige Hertie-Stiftung, untilbecoming Chair of the Department of Neurology, University of Bochum at St. Josef-Spital, in August 2006. Here, the annual numberof patients with MS comes to more than 1200 outpatients and 800 inpatients. His department performs independent laboratorytesting for neutralizing autoantibodies against natalizumab in Germany and some other countries. Dr Gold’s main scientific interestis in translational therapies for MS, experimental immunotherapies in animal models of MS and Guillain–Barré syndrome, andneurobiological disease modulators. He serves as the leading clinical physician and as Principal Investigator in a number ofcontrolled therapeutic trials in MS, and is involved in several scientific research programmes and advisory boards. Currently he isa member of the ECTRIMS Executive Committee and the German Neurological Society board, and is panel leader of the EFNSDemyelinating Diseases Section. Recently he coordinated the update of the German Neurological Society MS guidelines. Dr Gold isa member of several societies, including the German Society for Neurology, the American Academy of Neurology and the AdvisoryBoard of the German MS Society. He has received several scientific awards for his experimental and clinical studies. He alsocontributes to several editorial boards. From his scientific work, more than 200 original publications and 80 review articles have beenpublished.

Lucia MoiolaDiscussant: Session II

Department of NeurologyInstitute of Experimental NeurologyVita-Salute San Raffaele University, Milan, Italy

Lucia Moiola received a degree in medicine in 1989 and a neurological certification in 1996, both from Milan University. She obtainedher PhD in 1996 from the University of Milan. In 1989, she joined the Department of Neurology at the Scientific Institute San Raffaele,Milan University, as a student, and then in 1999 as a Clinical Assistant. Dr Moiola is currently the Outpatient Area Coordinator at theDay Hospital of the Neurological Department, Scientific Institute San Raffaele, Milan. Dr Moiola’s research interests are principallywithin inflammatory-demyelinating pathologies of the CNS, in particular MS: immunology, epidemiology, genetics, diagnosis andtreatment. She has wide experience in clinical trials of new agents for MS. She is a member of the Italian Paediatric MS Study Group.Furthermore, she has experiences in “NMO spectrum disorder”: immunology, epidemiology, diagnosis and treatment for Devicdisease and limited forms of neuromyelitis optica. She is also interested in primary and secondary CNS vasculitis, and in particularprimary angiitis of the CNS. Dr Moiola has authored and co-authored about 100 papers in peer-reviewed scientific journals.

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Dawn LangdonSpeaker: Session IV / Presenter: Session IV

Department of PsychologyRoyal Holloway University of LondonLondon, UK

Dawn Langdon completed her training as a Clinical Psychologist at Oxford University, Oxford, and the Institute of Psychiatry, London.She worked as a Clinical Neuropsychologist at the National Hospital, Queen Square, London, obtaining a PhD on reasoning inorganic brain syndromes. She is a registered Neuropsychologist and a Health Psychologist. Dr Langdon is now a Professor ofNeuropsychology at Royal Holloway, University of London and neuropsychology lead on a number of multinational trials. Herresearch work centres on psychological aspects of MS and current projects include the efficacy of medication in protecting cognition,cognitive rehabilitation, cognitive profiles in clinically isolated syndrome and early MS, and cognition in the later stages of MS,including its relation to early disease status. Dr Langdon is a frequent contributor to international scientific meetings andcommittees and is a Trustee of the UK MS Trust, with whom she has authored the MS cognition website www.stayingsmart.org.uk.She is co-chair of the BICAMS project.

Biographies

Jorge OksenbergSpeaker: Session III

Department of NeurologyUniversity of California at San Francisco (UCSF)San Francisco, USA

Jorge Oksenberg holds the G. Zimmermann Endowed Chair in Neurology and is Professor of Neurology at the University of Californiain San Francisco (UCSF). Dr. Oksenberg received his PhD in immunology in 1987 from the Hebrew University of Jerusalem, Israel,and joined the UCSF faculty in 1993 following post-doctoral training at Stanford University, California. Dr Oksenberg is a leadinginvestigator in the multicentre Multiple Sclerosis Genetics Group and the International Multiple Sclerosis Genetics Consortium. Dr.Oksenberg has published over 200 peer-reviewed articles and scholarly reviews, and serves as associate editor for the Annals ofNeurology.

Peter RieckmannPresenter: Session II / Speaker: Session IV / Discussant: Session IV

Bamberg Hospital and University of ErlangenBamberg, Germany

Peter Rieckmann received his medical degree from the University of Göttingen, Germany, in 1998. After a postdoctoral fellowship inmolecular immunology at the NIH, Bethesda, USA, he completed his training in Neurology at the National Institute for NervousDisease, London, UK, and the University of Göttingen. Professor Rieckmann received Board certification in Neurology in 1995; hisacademic and clinical positions have included Senior (staff) Neurologist and Professor for Neurology, Department of Neurology, aswell as Head of the Clinical Research Group for Multiple Sclerosis and Neuroimmunology, at the Julius-Maximilians University ofWürzburg, Germany. He holds several position as visiting professor across the globe. In 2007 Professor Rieckmann became the MSSociety of Canada Research Chair and Director of the MS Program at the University of British Columbia and Vancouver Hospital,Canada. Under his leadership the Vancouver programme was awarded Western-Pacific Research and Training Center by the MSSociety of Canada. He is founding member of the EndMS campaign in Canada. Professor Rieckmann’s major research interests aredisease-modifying factors and regeneration in MS, as well as functional aspects of the blood–brain barrier in neuroimmunologicaldiseases. Professor Rieckmann’s clinical goals include enhancing awareness and education about MS, developing effective andproperly resourced services for MS outpatient care, and providing more customized treatments for patients. As a clinician scientisthe has been actively involved in different efforts to transfer bench results to clinical developments, and serves on steeringcommittees of various international multicentre MS trials (Phase II and III). In September 2009 he started a new position as Directorof the Neurological Clinic at the Academic Hospital in Bamberg, and Professor of Neurology at the University of Erlangen, Germany,but will continue his Research Chair at UBC, Vancouver. Professor Rieckmann is a Fellow of the Royal College of Physicians andSurgeons, Canada, and has received numerous awards and research grants. He has over 200 papers to his credit in peer-reviewedmedical journals.

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Alex RoviraSpeaker: Session III


Alex Rovira is a full-time neuroradiologist who received his medical degree in 1983 from the Autonomos University of Barcelona.After formal training in radiology at Vall d’Hebron University Hospital, Barcelona, he undertook a visiting fellowship at ShandsHospital, Gainesville, University of Florida, in 1989. In 1990 he became staff neuroradiologist at the Vall d’Hebron University Hospital,and since 1991, is Director of the Magnetic Resonance Unit of the Department of Radiology. In 2007 Dr Rovira obtained the EuropeanQualification in Neuroradiology issued by the European Board of Neuroradiology.

Jaume Sastre-GarrigaSpeaker: Session IV / Discussant: Session IV


Jaume Sastre-Garriga serves as a neurologist at the Unitat de Neuroimmunologia Clínica (UNIC), MS Centre of Catalonia (CEM-Cat), Hospital Vall d’Hebron (Barcelona). He is coauthor of 66 peer-reviewed papers and 11 book chapters or monographs; he hascoauthored more than 40 oral presentations and more than 70 poster presentations at national and international conferences. Heserves as a reviewer for Multiple Sclerosis, Neuroimage, Human Brain Mapping, Archives of Neurology and Neurología, and for theSpanish granting body Fondo de Investigaciones Sanitarias (FIS), the Italian MS Society (FISM), the Catholic University of Leuven(KUL) and the Spanish Neurological Society (SEN). He has served as faculty or organizer for more than 100 lectures, both to healthprofessionals and organizations for patients and their relatives. Dr Sastre-Garriga’s main interests are new magnetic resonanceimaging techniques (functional MRI and volumetry) and neurorehabilitation, with a special focus on the primary progressive formsof MS.

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Biographies

Alan J. ThompsonSpeaker: Session II

Department of Brain Repair and Rehabilitation, Institute of NeurologyUniversity College London, National Hospital for Neurology and Neurosurgery Queen Square, London, UK

Alan Thompson is Dean of the Faculty of Brain Sciences at University College London, and Programme Director for the NeurologicalDisorders theme of UCL Partners (Academic Health Science Centre). He is Garfield Weston Professor of Clinical Neurology andNeurorehabilitation at the UCL Institute of Neurology, and a consultant neurologist at the National Hospital for Neurology andNeurosurgery, Queen Square. His main area of expertise is demyelinating disease, particularly the diagnosis, evaluation andmanagement of MS. His research focuses on the pathological mechanisms that underpin neurological disability and recovery, usingstructural and functional imaging, and developing scientifically sound outcome measures that incorporate the patient’s perspective.He has published extensively in these areas. Through his role with UCL Partners, he has jointly led innovation in the treatmentpathways for stroke and brain cancer. Professor Thompson is a Senior Investigator for the National Institute for Health Research,Editor-in-Chief for Multiple Sclerosis Journal, chairman of the International Medical and Scientific Board of the Multiple SclerosisInternational Federation (MSIF), and a Guarantor of Brain. Professor Thompson received his undergraduate and postgraduatedegrees from Trinity College Dublin, Ireland, and has been awarded an honorary doctorate by Hasselt University, Belgium.

Mar TintorèSpeaker: Session II


Mar Tintorè is co-founder and senior neurologist at the Unitat de Neuroimmunologia Clínica (UNiC), MS Centre of Catalonia (CEM-Cat), Hospital Vall d’Hebron, Barcelona, Spain. The unit follows a patient base of over 4000 patients with MS and receives about 600new cases for investigation, diagnosis and therapy. The unit sees about 120 patients each week, 20 of whom are new referrals. At present, Phase II, III and IV clinical trials are being conducted at UNiC. Dr Tintorè’s main line of research at UNiC is based on firstpresentations of demyelinating events, magnetic resonance, immunological aspects and MS treatment. Dr Tintorè is currentlyinvolved in the furthering of the European MAGNIMS research programme, which studies magnetic resonance in clinically isolatedsyndromes (CIS) and early MS. Dr Tintorè also has an interest in other aspects of MS, such as fatigue and its immunological features,which has gained funding from national research agencies. Dr Tintorè’s work on CIS and development to MS has been referencedin the published McDonald diagnostic criteria. Dr Tintorè has authored over 100 publications in national and international peer-reviewed journals, and serves as a reviewer for national and international journals and national research support and fundingagencies.

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Antonio UccelliSpeaker: Session I

MS Clinic and Neuroimmunology Unit Department of Neuroscience, Ophthalmology and GeneticsUniversity of Genoa, Genoa, Italy

Antonio Uccelli was born in Genoa, Italy, in 1964, where he obtained his medical doctoral degree in 1987. He completed his residencyin neurology at the University of Genoa in 1993. In 1992 he was a post-doctoral fellow in the Laboratory of Neuroimmunology,Department of Neurology, University of California San Francisco (UCSF), directed by Professor S.L. Hauser. In 1993 he obtained afaculty position in the Department of Neurology at the University of Genoa. Since 1995 Professor Uccelli has been the Director of theNeuroimmunology Unit of his Department, focusing his research activities on MS and more recently on adult stem cells. In 2001 hewas awarded the Rita Levi Montalcini Award, presented every year to the best Italian researcher in the field of MS. In 2001 he joinedthe Center of Excellence for Biomedical Research at the University of Genoa, directed by Professor Benatti. In 2008 he became theDirector of the Neuroimmunobiology Laboratory of the Advanced Biotechnology Center of Genoa, and in 2009 the Director of theCenter for Research and Cure of Multiple Sclerosis of the University of Genoa. Since February 2012 he is the Director of theResidency School of Neurosurgery at the University of Genoa. He is also an Associate Professor of Neurology at the University ofGenoa since December 2011. Professor Uccelli is co-author of 100 peer-reviewed scientific publications and has been invited to giveseminars and keynote lectures at many academic sites and conferences all over the world. Since 1995 he has received numerousscientific grants from national and international agencies.

Patrick VermerschSpeaker: Session I

Department of Neurology University of LilleLille, France

Patrick Vermersch studied medicine at the University Hospital in Lille, France, where he graduated with a medical thesis concerningthe correlations between postural and oculomotor disturbances in Parkinson’s disease. He then completed his education in morebasic fields, mainly in cellular biology from 1990 to 1994 with a PhD focused on biochemical abnormalities associated withAlzheimer’s disease and other neurodegenerative diseases. Professor Vermersch has also conducted research related to thecharacterisations of post-transcriptional anomalies of Tau proteins. His research interests then turned to MS. Professor Vermerschis Head of one of the Departments of Neurology, University of Lille, France, which deals with MS and other neuro-inflammatorydiseases. The principal scientific interests of the department are neuroimmunology and markers of disease evolution. ProfessorVermersch is President of the Scientific Committee of the University Hospital. He was Vice-President of the Regional ScientificConsultative Committee of INSERM (Institut National de la Santé et de la Recherche Medicale) from 1994 to 1996. In 2000 he createdthe first MS network in northern France to improve both care and research in MS. Professor Vermersch’s main areas of interest areprognostic markers of MS and neuroimmunology in general. He participates in many clinical trials in MS and as author or co-author,he has published approximately 260 scientific papers.

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Abstracts

L1 - Improving understanding of mechanism of action ofimmunomodulatory drugs

The mechanism of action (MOA) of any drug has major implications for its efficacy and safety profile, whatever the therapeutic area.In MS, work to characterize the MOA of the disease modifying drugs (DMD) interferon beta and glatiramer acetate has been ongoingfor many years. Evidence is emerging that these drugs have complex, multifactorial mechanisms, involving multiple aspects of theinnate and acquired immune system. Natalizumab and fingolimod have more recently become available for the treatment of MS. Incontrast to immunomodulatory mechanisms of interferon beta and glatiramer acetate, both of these drugs affect MS pathology bylimiting entry of activated immune cells to the central nervous system, although by different mechanisms, which are reflected ineach drug’s efficacy and safety profile.

This presentation will summarize what is known about the MOA of the currently available treatments for MS, as well as the proposedMOAs of DMDs still in development. The adverse event profile of a drug is intimately linked to the MOA and the clinical implicationsof this for current and new drugs will be discussed. The hope is that in the future a full understanding of the MOA of each availabledrug may translate to more informed treatment decisions to suit individual patients.

Bernd C. KieseierDepartment of Neurology, Heinrich-Heine University, Dus̈seldorf, Germany

References:1 - Xxx xxxxxxxxxx. Human Reproduction 6 1206-1212. 2 - Xxx xxxxxxxxxx et al. .

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L2 - Neuroprotection and steps towardsneuroregeneration: promising therapeutic targets

In view of the limited efficacy of immunotherapies for MS, especially in the later progressive stages of the disease, there are ongoingattempts to develop neuroprotective drugs that may also have immunomodulatory functions. Amongst them are laquinimod,fumarate (BG12) and fingolimod.

Laquinimod is a promising, orally available compound that was successfully evaluated in placebo-controlled Phase II/III studies inrelapsing–remitting MS (RRMS). Furthermore, analyses in the animal model of experimental autoimmune encephalomyelitis (EAE)demonstrate that laquinimod reduces infiltration of leukocytes into the central nervous system (CNS), induces a Th1 to Th2/3 shift,and has a potential neuroprotective capacity via modulation of brain-derived neurotrophic factor. In particular, modulation ofmonocytes by laquinimod mediates this neuroprotection, and it has been translated in clinical studies where brain atrophy wasclearly diminished in patients exposed to laquinimod for 2 years.

Fumaric acid was originally used therapeutically in psoriasis. Several lines of evidence have demonstrated both immunomodulatoryand neuroprotective effects of fumaric acid. Animal experiments in the mouse model of the CNS, myelin oligodendrocyteglycoprotein-induced EAE, revealed a clear preservation of myelin and axonal density in EAE plaques. Molecular studies showed thatthis resulted from an antioxidative effect via induction of the transcription factor Nrf-2. A Phase II clinical trial of dimethylfumarate(BG12) in patients with RRMS showed a significant reduction in the number of gadolinium-enhancing lesions after 24 weeks, andthis has recently been complemented by two Phase III, trials where a 50% reduction in relapse rate was observed compared withthe placebo group.

With fingolimod, the pluripotent action on S1P receptors not only mediates the sequestration of lymphocytes into peripheral immuneorgans, but also has the potential to stimulate oligodendrocytes for remeylination.

In addition to these drugs, novel approaches to enhance neurorepair will be discussed.

Ralf GoldUniversity of Bochum, Bochum, Germany

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L3 - Resetting the immune system: stem celltransplantation

Recent advances in our understanding of stem cell biology, such as the availability of innovative techniques, which allow stem cellsto be obtained on a large scale, and the increasing pressure from patients for tissue repair strategies, have launched stem celltreatments as one of the most exciting and difficult challenges in the MS field. Here, an overview of the current status of stem cellresearch in MS is provided, focusing on confirmed advances, reasonable hopes and unrealistic myths.

Results obtained from small clinical studies of transplantation of autologous hematopoietic stem cells have demonstrated that thisprocedure is feasible and possibly effective in severe forms of MS, but tackles only inflammation without affecting tissueregeneration. Results from preclinical studies with other adult stem cells such as bone marrow derived mesenchymal stem cellshave shown that they may be a powerful tool to regulate pathogenic immune response and possibly foster tissue repair. However,the possible clinical translation of these results still requires careful evaluation.

Therefore, current experimental evidence suggests that the sound clinical exploitation of stem cells for MS may lead to novelstrategies aimed at blocking uncontrolled inflammation, resetting the immune system, protecting neurons and promotingremyelination, but not at restoring the chronically deranged neural network responsible for irreversible disability typical of the latephase of MS.

Antonio UccelliMS Clinic and Neuroimmunology Unit, Department of Neuroscience, Ophthalmology and Genetics,University of Genoa, Genoa, Italy

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L4 - Efficacy profiles of MS drugs

For almost 20 years, clinicians have been able to treat MS with disease-modifying drugs (DMDs) with the intention of reducing orarresting the progression of physical disability. Today’s neurologists are familiar with the efficacy and safety profiles of the“established” immunomodulatory DMDs. The arrival of newer drugs on the one hand offers additional therapeutic options, and onthe other presents uncertainty regarding optimal treatment algorithms and the longer-term safety of new drugs.

This presentation will give an overview of the safety and efficacy profiles of the available DMDs for MS, then discuss how thisinformation allows the design of treatment algorithms that can be tailored to the needs of the individual patient. In MS there are twoapproaches to sequential use of DMDs: the escalation approach begins with the use of the established immunomodulators and, inthe event of breakthrough disease, steps up to more potent and potentially more dangerous agents; with the induction approach, amore potent drug usually with a higher risk profile is used initially for a limited period, followed by maintenance therapy with animmunomodulator.

As more DMDs become available for MS, the potential sequencing becomes increasingly complex and it is important to take intoaccount prognostic factors before determining the most appropriate algorithm for each patient. Furthermore, depending on themechanisms of action of available drugs, combination regimens may soon be possible. These themes will be discussed in thispresentation to clarify how the clinician can use the range of available drugs to create treatment schemes that are optimally effectivefor each patient, while minimizing risk.

Giancarlo ComiDepartment of Neurology, Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy

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L5 - Monitoring drug safety in clinical practice

The past two decades have seen tremendous expansion in therapeutic options for patients with relapsing forms of MS. While thegrowing armamentarium of therapies provides physicians and patients an array of available options, it also brings in its wake thechallenging responsibility of choosing the optimal therapy for an individual patient. Interferon beta and glatiramer acetate aregenerally considered the first-line drugs in relapsing MS and have well-characterized safety profiles. However, these drugs are notoptimally effective in all patients. Potentially more potent drugs are also available, but the benefit of heightened efficacy must beweighed carefully against increased risks. Several strategies have been proposed with the aim of minimizing these risks. To improveadherence to therapy, it is important to educate patients regarding adverse events (AEs) and to manage AEs proactively.

The greatest risk for patients receiving mitoxantrone is cardiotoxicity; thus, the cumulative dose is limited. A systematic cardiacevaluation including echography or scintigraphy is important before mitoxantrone treatment and 6-monthly or annually for at least5 years after treatment. Additionally, regular blood tests are recommended to detect sustained lymphopenia or neutropenia.

Allergic reactions can occur with natalizumab, and there is a risk of progressive multifocal leukoencephalopathy (PML). Clinicalvigilance is crucial to detect early signs of susceptibility. Natalizumab treatment duration and prior use of immunosuppressivetherapies are established risk factors for PML in patients who test positive for the John Cunningham Virus (JCV). Recommendationsfor the clinical management of patients with MS and use of natalizumab are provided based on the presence of these three riskfactors. Expertise in magnetic resonance imaging (MRI) monitoring techniques is fundamental in following patients at risk of PML.Different protocols for MRI monitoring are recommended depending on the risk of PML.

Very recently the European Medicines Agency gave new advice to healthcare professionals to reduce the risk of adverse effects onthe heart associated with the use of fingolimod. The Agency’s Committee for Medicinal Products for Human Use recommends thatall patients starting treatment with fingolimod should have their heart activity monitored before receiving the first dose of themedicine and continuously for at least 6 hours after. Monitoring should be extended for at least 2 hours in patients whose heart rateis lowest 6 hours after receiving the first dose of fingolimod. In patients who develop clinically significant heart problems, such asbradycardia or atrioventricular block, monitoring should continue at least overnight and until the problems have been resolved.Fingolimod-associated macular oedema has been noted in fingolimod trials but appears to be dose-dependent and very rare withthe approved 0.5 mg dose. In patients with diabetes or history of uveitis, an ophtalmologic examination is required before treatmentonset, after 3 months and thereafter if necessary. The authorities have also given various other recommendations for fingolimodtreatment, such as prohibited drug combinations, vaccination, contraception and blood tests specifically for lymphocyte counts andliver functions every 3 months for the first year of treatment and periodically thereafter. Safety needs to be considered a priority.Considering these risks and the possible approval of new drugs in the near future, each with specific safety issues, it is vital thatexperts promote educational therapeutic programmes for neurologists, other physicians potentially involved, nurses and patients.

Patrick VermerschDepartment of Neurology, University of Lille, Lille, France


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L6 - McDonald criteria 2010: making the diagnosiseasier

The diagnosis of MS remains firmly based on clinical evaluation and the essential need to provide evidence for dissemination in timeand space and, importantly, to exclude other neurological conditions that could cause similar symptoms. While investigations areimportant to exclude other conditions, the interpretation of their results will only be as good as the clinical premise on which theyare based. The evolution of diagnostic criteria since Poser in 1983 has focused on improved definition and greater precision. Theintroduction of magnetic resonance imaging (MRI) has had a major impact on both the timing and accuracy of diagnosis. The initialMcDonald criteria (2000) incorporated MRI for the first time and were very cautious in order to maximise specificity. Theyincorporated the Barkhof criteria to determine dissemination in space and time, but these criteria are complex, and not easilyapplied. Criteria for primary progressive MS (PPMS) were distinct and had even less evidence base. The subsequent revisions of theMcDonald criteria in 2005 and 2010 simplified the MRI criteria for dissemination in both time and space, based on sound studies,reduced the emphasis on cerebrospinal fluid findings in PPMS and drew more closely together the criteria for the relapsing andprogressive forms of the condition. In addition, the recent 2010 version, addresses, for the first time, the complexities of neuromyelitisoptica and the spectrum of related disorders, in addition to the topical issue of paediatric MS.

Alan J. ThompsonDepartment of Brain Repair and Rehabilitation, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery Queen Square, London, UK

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L7 - The diagnosis of MS before MS

Diagnosis of MS relies on the presence of symptoms suggestive of MS, together with evidence of dissemination of disease in spaceand time and reasonable exclusion of other causes. The introduction of the McDonald 2001 criteria, first allowed magnetic resonanceimaging (MRI) evidence of diagnosis for dissemination in space and time to contribute to a diagnosis in patients with a first attack.The recently published 2010 McDonald criteria allow for even earlier diagnosis with evidence of dissemination in space and timefrom a single MRI scan. In recent years, there has been an increase in the use of MRI as a diagnostic in neurology. This has resultedin the more frequent discovery of brain pathologies in the absence of clinical manifestation, but nevertheless with potential clinicalsignificance. This raises the question of how to categorize and treat the asymptomatic patient when such subclinical evidence ofdisease fulfils MRI criteria for dissemination in space and time. Recent studies indicate that these patients, labelled as having“radiologically isolated syndromes” or RIS, are at risk for developing MS in the following years. A diagnostic and therapeuticapproach for patients with RIS will be discussed.

Mar TintorèMultiple Sclerosis Center of Catalonia, Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain

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L8 - What can magnetic resonance imaging tell us aboutdisease evolution in the individual patient?

Magnetic resonance imaging (MRI) allows reproducible and objective measurement of brain tissue damage in MS. It is used as adiagnostic tool to follow the course of the disease and monitor response to treatment, and can be considered the best markercurrently available for MS pathology. Despite the usefulness of MRI, it is generally accepted that there is poor correlation betweenMRI disease measures and MS clinical symptoms and disability – a discrepancy commonly referred to as the “clinical–MRI paradox”.

Nevertheless, there are indications from long-term longitudinal studies that an increase in the volume of brain lesions – asmeasured by T2-weighted MRI – during the early stages of MS correlates with the degree of long-term disability. Recent analysesof data from published randomized clinical trials have also validated the use of MRI lesions as surrogate measures for relapses anddisability progression, both at the trial level and at the individual patient level. In addition, it has been observed that a high proportionof the variance seen between trials in relapse outcomes can be explained by variance in MRI measures.

Such findings will be discussed in this presentation, taking into account their implications for patient management in clinical practiceand in particular how they may modify the current approach to the use of MRI in the individual patient. Future research requirementsto further elucidate the correlations between MRI measures and MS disability will also be considered.

Douglas ArnoldMontreal Neurological Institute and Hospital, Montreal, Canada


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C1 - Case study: Differential diagnosis - neuromyelitis optica vsMS

Evidence is increasing that MS and neuromyelitis optica (NMO) represent discrete disorders that both affect the central nervoussystem. NMO typically presents with spinal cord and optic nerve involvement; diagnosis is supported by the presence of NMO–immunoglobulin G antibodies against the aquaporin 4 (AQP4) channel. Although once considered unusual in patients with NMO,brain lesions can be observed, but these lesions have different characteristics from the ones described in MS. Additionally, someAQP4 antibody-positive patients may present with a variety of symptoms, such as optic neuritis and acute myelitis during the firstattack or relapses. Even though MS and NMO may represent distinct diseases, differential diagnosis remains challenging. Moreover,a prompt diagnosis is fundamental in order to provide early treatment to limit subsequent disability progression. This case studysession will be an opportunity to share opinions about MS and NMO and their differential phenotypes, starting with a discussion ofan atypical clinical case with a challenging diagnosis.

A case study on this topic will be presented by P. Rieckmann (Germany)and discussed with: L. Moiola (Italy)

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L9 - Biomarkers

The extreme variability that characterizes the natural history and clinical manifestations of MS has lead to extensive research effortsaimed at identifying reliable disease biomarkers in the blood and cerebrospinal fluid. Establishing robust biomarkers could enhanceMS diagnostics and provide a source of useful information to predict and monitor disease development and progression, responseto treatment, and a patient’s possible predisposition for adverse events. Ideal biomarkers should be disease-specific, sensitive andallow rapid and accurate detection and quantification of pathological features.

It is known that genetic polymorphisms, such as major histocompatibility complex class II and III gene variants, are associated withMS susceptibility and disease course, although data are inconsistent across populations. Markers of immune activation have beenidentified, and proteins indicative of demyelination and neuronal damage are under investigation as potential biomarkers of diseaseprogression. Molecules that reflect drug bioavailability are also being studied. In addition, the use of microarray technologies forgene expression analyses and microRNA profiling techniques have recently facilitated the identification of promising biomarkercandidates.

Despite the undeniable progress made in recent years, further research is necessary for biomarkers to become a comprehensivediagnostic and monitoring tool in MS; in particular, the identification of reliable markers of neurodegeneration and diseaseprogression remains an unmet need. This presentation will provide an overview of the current knowledge of biomarkers in MS,discussing their limitations and outlining the most promising areas of research in the field.

Gavin GiovannoniDepartment of Neurology, The Royal London Hospital, Whitechapel, London, UK

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L10 - MRI as a potential marker of treatment responsein current clinical practice

Magnetic resonance imaging (MRI) measures of inflammatory activity, such as gadolinium-enhanced T1- and T2-weightedsequences, are highly sensitive for detecting MS plaques. Such measures strongly predict the effect of treatment on MS relapses,supporting the use of conventional MRI as a biomarker for treatment response, not only in clinical trials but also in clinical practice.Patients with MS who continue to experience clinical or MRI activity despite treatment with disease-modifying drugs (DMDs) areconsidered non-responders, although individually it is difficult to establish whether a given patient presents a good response totreatment, and if so to what degree. To optimize MS therapy, early identification of those patients who will be non-responders isimportant. To this end it may be necessary to evaluate the contribution of MRI scans performed at DMD initiation and during follow-up, toward the identification of such non-responders. Recent data have shown that the presence of more than two active lesions(new or enlarging T2 plus gadolinium-enhancing brain lesions) on a brain MRI scan performed 12 months after therapy initiation isthe strongest MRI predictor of treatment response, indicating a high risk of clinical activity and disease progression in the followingyears. The arrival of new therapeutic options in the forthcoming years will probably increase the need for accurate biomarkers, suchas MRI, to predict treatment response in individual patients.

Alex RoviraMultiple Sclerosis Center of Catalonia, Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain


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L11 - Present and future roles of pharmacogenomics

Genetic polymorphisms and variable expression of drug receptors, metabolizing enzymes and transporters have been linked tointerindividual differences in the efficacy and toxicity of many therapeutic agents. The term pharmacogenetics, a subclass ofpharmacogenomics, was coined initially in 1959 by Friedrich Vogel and is now defined by the US Food and Drug Administration as“the study of variations in DNA sequence as related to drug response”; these variants include single nucleotide polymorphisms andcopy number variations. The contemporary definition of pharmacogenomics extends beyond common germline variants to includelow-frequency variants, RNA expression, epistasis and epigenetic regulations. In MS, the combination of heterogeneity of diseasepresentation and the significant variation in clinical response to disease-modifying agents necessitates the definition ofpharmacogenomic biomarkers that can a priori predict therapeutic response and define appropriate therapeutic regimens, toensure optimal clinical response, patient compliance and protection against the more severe side effects. Achieving adequatepredictive specificity and sensitivity will undoubtedly require integration of data from all aspects of MS research, including clinical,genetic and environmental data, coupled with the application of advanced integrative approaches such as dynamic systemsmodelling. This effort will be challenged further by the introduction of new therapeutic agents and the establishment of combinationtherapies. We will critically review the current pharmacogenomics knowledge of MS, addressing DNA variants and gene-expressionsignatures reported to correlate with therapeutic responses, and discuss the options available to incorporate pharmacogenomicsinto routine clinical practice.

Jorge OksenbergDepartment of Neurology, University of California at San Francisco (UCSF), San Francisco, USA


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L12 - Assessment of treatment response

The “window of opportunity” for treatment is different for each patient with MS. There are now many possible agents to offerindividuals with relapsing forms of MS, but there is still no validated way of finding the most suitable agent for any one patient otherthan a “hit-and-miss” approach. It is hoped that some biomarkers will soon identify therapies that might be ineffective in certainindividuals and therefore avoided so as not to waste precious treatment time. Somewhat empirically, therefore, we must choose theagent most appropriate to where we feel a patient lies within the “window” and monitor treatment response accordingly. Although,with the “right” treatment approach, it might be possible to keep patients 100% disease activity-free today, given that no treatmentis a “cure”: some disease activity may be inevitable. It is important to determine what type, or to what degree, of breakthroughdisease warrants a change in treatment. There are now many intelligent, logical approaches to monitoring treatment response –but they must be reasonable, feasible and truly informative. Clearly, detecting disease activity is a reflection of the number of timesone “looks” for it – a product of how often patients are contacted, examined or imaging performed. Assessing treatment responseis not as simple as recording how often patients experience a relapse. The severity, response to steroids and ultimate recovery mustalso be taken into account, as should the number of MS lesions, their location in the central nervous system and accompanimentof Expanded Disability Status Scale progression. These factors are all important when deciding whether to maintain the presenttreatment regimen, or to adjust the approach. This may be especially true if the decision to “switch” treatment may require movingto a more toxic agent, posing risks to health that may be greater than the MS disease itself. All of this is, of course, dependant onwhether a particular therapy is tolerated and adhered to by patients, both of which are key to optimizing treatment response. Usingmodels that place weight on the quantity and quality of events occurring while tolerating and adhering to a particular therapy, itmight be possible now to determine when it might be best to stop a particular treatment, as well as provide guidance as to whatshould be tried next. These types of treatment algorithms are evolving as we acquire and appreciate the benefits (and risks) of newertreatments.

Mark S. FreedmanMultiple Sclerosis Research Unit, The Ottawa Hospital, Ottawa, Canada

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C2 - Case study: Treatment and treatment algorithms

The clinical presentation and disease course of MS differ between patients, ranging from “benign” forms of MS to more aggressiveones. Several therapeutic options are now available; in addition to the well-known first-line treatments interferon beta andglatiramer acetate, several oral disease-modifying therapies are now available or are in development. Oral treatments have shownbenefit and have generated much interest because of the convenience of oral administration. However, the availability of oral drugswill not necessarily translate into increased clinical effectiveness and safety. This major advance will bring new options to patientsbut will present neurologists with both opportunities and challenges when selecting the best therapeutic approach for their patients,taking into account both effectiveness and side effects of the new drugs.

The widening of therapeutic options and the diverse clinical presentations and disease courses of MS make treatment selectionmore difficult than in the past, both for neurologists and patients. In this session we will discuss treatment options and treatmentalgorithms with reference to real clinical examples.

A case study on this topic will be presented by G. Comi (Italy)and discussed with: X. Montalban and O. Fernández (Spain)

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L13 - The patient’s willingness to take risk

As in any therapeutic area, the benefits deriving from the use of pharmacological treatment for MS are accompanied by associatedrisks; the range of benefits and risks is unique for each therapeutic approach, and need to be taken into account when consideringtreatment options for the patient.

Established disease-modifying drugs (DMDs) for MS – such as interferon beta and glatiramer acetate – have well known andgenerally favourable safety profiles based on experience from nearly 20 years of clinical use. Newer agents offer the advantage ofimproved efficacy and more convenient routes of administration, but their use is limited by increased safety risk and the lack of long-term toxicity data. Natalizumab, for example, increases the risk of progressive multifocal leukoencephalopathy, while mitoxantroneis associated with cardiotoxicity and fingolimod with cardiological adverse events.

Consideration of the patient’s perception and willingness to take risk is paramount in order to effectively assist them in making aninformed choice about their treatment. Several factors can influence the patient’s attitude towards risk, including gender (men are,in general, more risk-tolerant), age, disease severity, disability and previous experience with DMDs. Each individual case is differentand needs to be carefully assessed, because the physician’s perception of risk can be substantially different from the patient’s.

Effective patient–physician communication is therefore vital, and it has to be taken into account that the way in which information ispresented may influence the patient’s decisions. Such issues will be discussed in this presentation, with the aim of helping cliniciansapproach the selection of the most appropriate therapy in consultation with the patient.

Peter RieckmannBamberg Hospital and University of Erlangen, Bamberg, Germany

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L14 - How to implement the patient–caregiverpartnership in clinical practice

There are several key aspects to the partnership between the healthcare professional and the patient with MS, which can facilitateoptimal clinical care. First, there must be mutual respect and consideration, which may need to be explicitly acknowledged. Second,communication must be effective. This needs to take account of the health literacy, cognitive status, mood and illness representationof the patient. Illness representation is the conceptual framework that the patient uses to understand their illness experience,including information and advice received from healthcare professionals. It is also important to establish the level of collaborationthat the patient would prefer in their treatment decisions. Given the likelihood that treatment adherence will not be 100%, it is helpfulif potential barriers to adherence are discussed initially, inviting the patient to raise problems that they may encounter whenimplementing medication regimes, or other healthcare management. Once an honest, open and accepting relationship isestablished, problems can be raised and addressed appropriately and healthcare optimized.

Dawn LangdonDepartment of Psychology, Royal Holloway University of London, London, UK

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L15 - Treatment adherence: how to measure it and howto improve it

Evidence from a large number of clinical trials has clearly demonstrated the benefit of immunomodulatory therapies in MS. It is alsoclear that the therapies available currently are not without side effects, and their modes of administration can still be cumbersomefor some patients. Additionally, the first-line immunomodulatory drugs are only partially effective in some patients, and negativeoutcomes such as relapses and progression of disability are still to be expected. Overall, these factors affect adherence to treatment,and poor adherence may render the therapeutic efforts futile. Most studies focusing on adherence have used as an outcome thenumber of patients who stop therapy with a given drug; others have investigated the number of missing doses. Several studies usingthe first approach have shown that most drop-outs occur in the early phases of therapy; in this regard, management of side effectsof therapies, which is most important at therapy onset, is crucial, as it is responsible for almost half of all discontinuations. The side-effects profiles of interferon (IFN)-beta preparations and glatiramer acetate are not identical. In the case of IFN-beta preparations,it is especially important to manage flu-like symptoms at onset of therapy. Several strategies can be implemented to diminish patientdiscomfort, such as gradual dose increase and concomitant use of non-steroidal anti-inflammatory drugs. Other side effects, suchas injection-site reactions, flushing and laboratory abnormalities, also need to be monitored closely. Another important factorrelated to treatment discontinuation is perceived lack of efficacy as a consequence of patients having unrealistic expectations oftreatment effects; therefore, proper management of treatment expectations is needed from the outset of treatment with disease-modifying drugs. Initiation of nurse-led patient education may be helpful to manage patients’ expectations and to anticipate andreduce the impact of side effects on adherence to treatment. In any case, individualized monitoring of treatment adherence is highlyrecommended in clinical daily practice to achieve the levels of efficacy seen in clinical trials.

Jaume Sastre-GarrigaMultiple Sclerosis Center of Catalonia, Unit of Clinical Neuroimmunology, Vall d’Hebron University Hospital, Barcelona, Spain


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C3 - Case study: Treatment failure due to lack of adherence

In general, adherence to treatment is defined as the extent to which patients follow their prescribed treatment regimens. Adherencerates are higher in acute conditions than in chronic conditions requiring long-term treatment. The ability of physicians to recognizenon-adherence is poor, thus leading to a worsening of disease and eventually to death. As most neurological disorders have achronic course requiring long-term therapies, adherence to treatment is still a “hot topic” and challenging for the neurologist. Amultidisciplinary management approach is required to optimize adherence to treatment and, consequently, to achieve the besttherapeutic effects and ameliorate the clinical outcome.

This case study session will provide an opportunity to discuss the main obstacles to adherence, and to share opinions on how bestto foster adherence with the aim of achieving the best possible therapeutic effects.

A case study on this topic will be presented by D. Langdon (UK)and discussed with: P. Rieckmann (Germany) and J. Sastre-Garriga (Spain)


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C4 - Case study: Improved outcomes through tailored treatment

MS is a heterogeneous disease – disease course and clinical manifestations vary widely between patients, as well as in the individualpatient over time from first presentation with a clinically isolated syndrome to secondary progressive stages of MS. Therefore it isimportant to tailor the treatment approach for each patient at each stage of disease, taking into account their clinical signs ofdisease, present and predicted progression, response to treatment and tolerability issues. In every phase of the disease, severaltherapeutic options are available, and the most adequate choice is not obvious. This situation is made more complex by the rapidlygrowing number of treatments available for MS, By presenting real clinical examples, the participants will have the opportunity todiscuss this important issue, in order to improve their clinical practice, guided by top experts in this field.

A case study on this topic will be presented by D. Bates (UK)and discussed with: G. Giovannoni (UK) and P. Rieckmann (Germany)


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Disclosure of faculty relationships

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Serono Symposia International Foundation adheres to guidelines of the European Accreditation Council for Continuing MedicalEducation (EACCME) and all other professional organizations, as applicable, which state that programmes awarding continuingeducation credits must be balanced, independent, objective, and scientifically rigorous. Investigative and other uses for pharmaceuticalagents, medical devices, and other products (other than those uses indicated in approved product labeling/package insert for theproduct) may be presented in the programme (which may reflect clinical experience, the professional literature or other clinical sourcesknown to the presenter). We ask all presenters to provide participants with information about relationships with pharmaceutical ormedical equipment companies that may have relevance to their lectures. This policy is not intended to exclude faculty who haverelationships with such companies; it is only intended to inform participants of any potential conflicts so that participants may form theirown judgements, based on full disclosure of the facts. Further, all opinions and recommendations presented during the programmeand all programme-related materials neither imply an endorsement nor a recommendation on the part of Serono SymposiaInternational Foundation. All presentations represent solely the independent views of the presenters/authors.

The following faculty provided information regarding significant commercial relationships and/or discussions of investigational or non-EMEA/FDA-approved (off-label) uses of drugs:

Douglas Arnold He declared no potential conflict of interest.

David Bates He declared receipt of grants, honoraria, consultation fees and contracts from Merck Serono, Bayer andBiogen.

Bonaventura Casanova He declared no potential conflict of interest.

Giancarlo Comi He declared receipt of honoraria or consultation fees from SSIF, Merck Serono, Novartis, Bayer Schering,Biogen, Sanofi, Teva, Actelion.

Oscar Fernández He declared no potential conflict of interest.

Mark S. Freedman He declared receipt of research or educational grants from Bayer Healthcare, Genzyme, EMD Canada. Healso declared receipt of honoraria or consultation fees from Bayer Healthcare, Biogen Idec, EMD Canada,Novartis, Sanofi-Aventis, Teva, Canada Innovation. He is a member of the company advisory board or boardof directors for Bayer Healthcare, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Celgene.

Gavin Giovannoni He declared receipt of consulting fees from Bayer Schering Healthcare, Biogen Idec, Genzyme,GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratoires, Teva-Aventis, VertexPharmaceuticals, UCB Pharma, Pfizer.

Ralf Gold He declared receipt of grants and contracts from Biogen Idec, Teva, Merck Serono, Novartis. He alsodeclared receipt of honoraria or consultation fees from Biogen Idec, Teva, Merck Serono, Novartis, CSLBehring, Baxter, Bayer. He is a member of the company advisory board orboard of directors for Biogen Idec,Teva, Novartis, Baxter.

Bernd C. Kieseier He declared receipt of honoraria and financial support for research from Bayer Schering, Biogen Idec,Genzyme, Merck Serono, Novartis, Roche, Sanofi-Aventis, Talecris, Teva.

Dawn Langdon She declared receipt of grants, contracts, honoraria or consultation fees from Bayer Healthcare. She is amember of the company advisory board or board of directors for Bayer Healthcare. She declaredparticipation in a company-sponsored speakers bureau for SSIF, Biogen Idec, Bayer Healthcare. She alsodeclared benefits from a relationship with a commercial enterprise: Bayer Healthcare.

Lucia Moiola She declared no potential conflict of interest.

Xavier Montalban He declared receipt of honoraria or consultation fees: Bayer Schering, Biogen Idec, Merck-Serono,Novartis, Teva, Sanofi, Genzyme, Almirall.

Jorge Oksenberg He declared receipt of honoraria or consultation fees from Teva Pharmaceuticals.

Alex Rovira He declared receipt of honoraria or consultation fees from Bayer Schering Pharma, Merck Serono, TevaPharmaceutical Industries Ltd and Biogen Idec. He is also a member of the company advisory board orboard of directors for NeuroTEC, Bayer Schering Pharma and BTG International Ltd.

Jaume Sastre-Garriga He declared to be a member of the company advisory board or board of directors for Novartis. He alsodeclared participation in company-sponsored speakers bureau for SSIF, Merck Serono, Novartis, Teva,Eisai.

Alan J. Thompson He declared receipt of honoraria or consultation fees from Biogen Idec, Eisai, Merck Serono, DIGNABiotech, Novartis, SSIF, NIHR as a Senior Investigator. He is also a member of the company advisory board,or board of directors for MSIF International Medical and Scientific Board, NMSS Research ProgramsAdvisory Committee. He declared benefit from a relationship with commercial enterprises: SagePublications, Multiple Sclerosis Journal, Elsevier, Lancet.

Mar Tintorè She declared receipt of grants and contracts from Bayer Schering, Biogen Idec, Merck Serono, Teva,Sanofi-Aventis and Novartis. She also declared receipt of honoraria or consultation fees from BayerSchering, Biogen Idec, Merck Serono, Teva, Sanofi-Aventis and Novartis. She is a member of the companyadvisory board or board of directors for Teva and Biogen Idec.

Antonio Uccelli He declared receipt of grants and contracts from Merck Serono, Sanofi-Aventis, Biogen Idec, Novartis. Hedeclared receipt of honoraria or consultation fees from Genolech, Allergan, Biogen Idec, Biogen Dompè,CMSC, Merck Serono. He declared participation in company-sponsored speakers bureau for Merck Serono,Novartis, Sanofi-Aventis, Biogen Dompè.

Patrick Vermersch He declared receipt of grants and contracts from Biogen Idec, Merck Serono, Bayer and Sanofi. Hedeclared receipt of honoraria or consultation fees from Biogen Idec, Almirall, Novartis, Bayer, MerckSerono, Teva, Sanofi.

The following faculty have provided no information regarding significant relationship with commercial supporters and/or discussion ofinvestigational or non-EMEA/FDA-approved (off-label) uses of drugs as of 8 May 2012.

Peter Rieckmann

42

NOTES

NOTES

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Documents

2012 CME Annual meeting in multiple sclerosis “MS: from ... · 2012 annual continuing medical education (CME) accredited meeting: “MS: from disease management to patient management”