EDITION JULY 2014 EULAR 2014 PARIS...T helper (Thf) cells, an IL-21 producing T cell subpopulation promoting B-cell maturation, inducing class switching and affinity selection and

EMEUNEWS JULY14 PAGE1

EULAR 2014 PARIS

Oral Presentations and Posters

EMEUNET mentor-mentee at EULAR

EMEUNET Country liaison meeting

EMEUNET Impressions

EDUCATIONAL EVENTSAugust – October 2014

EDITION JULY 2014


Dear young rheumatologists and researchers in rheumatology,

once again the EMEUNET team welcomes you in this new issue of EMEUNEWS. The EULAR 2014 Congress was a great scientific event and in this issue we pro-vide a selection of oral presentations and posters that have been presented in the various clinical and research areas of our discipline. The selection is totally personal and therefore very limited and incomplete, but it still might give an overview of hot topics that have been discussed in each field.EULAR Congress was also an opportunity to meet and have fun! As last year, in ad-dition to the traditional EMEUNET Booth, a sightseeing tour to enjoy together the beauties of Paris and Paris’ nightlife was organized and it was a great success.For those of you who still don’t know, EMEUNET mem-bers can now stay in touch also via Facebook and the page is constantly growing with information and pictures.Finally, the current Newsletter also contains an update on EULAR projects in education and training and a calendar of some upcoming educational events. We hope that EMEUNET will continue to grow and reach more and more young rheumatologists and researchers over the next years. We would be happy if you, as EMEU-NET members, disseminate the existence and aims of EMEUNET to anybody who is interested. We hope that you enjoy reading this Newsletter and would be happy to receive any comments or contribu-tions for future issues.We wish you relaxing and pleasant summer holidays.

Your EMEUNET Newsletter SubgroupAlessia, Russka, João and Xenofon

EULAR 2014: ORAL PRESENTATIONS & POSTERS 4Basic research I Basic research IIRA IRA IIRA IIIPsoriatic ArthritisAxial SpondyloarthritisSLE & APSOther connective tissue diseasesImagingCrystal ArthropathiesOsteoarthritis & Osteoporosis

EMEUNET MENTOR-MENTEE AT EULAR 16

EMEUNET COUNTRY LIAISON MEETING 16

EDUCATIONAL EVENTS AUGUST-OCTOBER 17

DIRECTORY

EDITORIAL


ORAL PRESENTATIONS & POSTERS EULAR 2014, PARIS

BASIC RESEARCH I Genetics, cartilage/synovium, osteoimmunology, animal models

Mary Canavan, PhD, is a postdoctoral research fellow within the Translational Rheumatol-ogy Group in St Vincents University Hospital Dublin. She completed a PhD in Immunology and her research activity is focused on the immunopathology of rheumatoid arthritis with a specific interest in dendritic cells and synovial fibro-blasts.

Mary Canavan

This year at EULAR there were a diverse and exciting range of abstracts in the area of osteoimmunology and genetics.Specifically Schönbeck et al [SAT0564] investigated the potential immunomodula-tory role of human mesenchymal stromal cells (hMSC). Given their essential role in fracture healing they hypothesized that hMSC could limit inflammation via the expression of the Cytotoxic T lymphocyte antigen 4 (CTLA-4). hMSC were isolated from the bone marrow of patients under-going total hip replacement and pheno-typed by the expression of CD13, CD44, CD90, CD105 in addition to assessing their osteogenic and adipogenic differen-tiation. They showed for the first time by mRNA and protein that hMSC are capa-ble of expressing CTLA-4 and that at the protein level this expression is not altered by hypoxia.Pleštilová et al [SAT0565] presented a potential role for PIWIL4 in the activation of synovial fibroblasts in rheumatoid ar-thritis (RA) and osteoarthritis (OA). PIWIL proteins are known to form complexes with piwi interacting RNAs (piRNA) and in doing so can limit gene expression. This work showed a significant increase in the expression of PIWIL4 in PBMCs from RA patients compared to controls. PIWIL4 was inducible in both RASF and OASF by proinflammatory cytokine and TLR stimu-lation. Furthermore upon PIWIL4 silencing TNFα and IL-1β induced RASF prolifera-tion was decreased. This study provides

insight into a possible role for PIWIL4 in the activation of synovial fibroblasts in RA.Smith et al [THU0486] aimed to investi-gate entire genome profiles in patients pre and post biologic treatment in an effort to discriminate between responders and non-responders. BTN3A2 was highlighted as a potential response biomarker as this gene corresponded with the most discriminatory power within their analy-sis. BTN3A2 encodes a protein that is a member of the Butyrophilin family. These proteins act by preventing the release of IFNγ from T cells and also show strong domain similarity with the costimulatory markers CD80 and CD86.Finally Kim et al [THU0471] investigated the role of the type III histone deacetylase SIRT1 in DC maturation and subsequent collagen induced arthritis (CIA). SIRT1 is a known modulator of inflammatory re-sponses through deacetylation of histones however a specific role for this deacety-lase in DC biology has not been exten-sively explored. CIA was induced in WT mice and myeloid specific SIRT1 KO mice after which severity of disease, destruc-tion and immunopathology where inves-tigated. mSIRT1 KO showed decreased disease severity and joint destruction in addition to decreased Th1, Th17 and CD80/CD86 positive DC therefore sug-gesting a role for SIRT1 in DC maturation and T cell differentiation in the context of RA.



BASIC RESEARCH IIImmunity, immunology

Alessia Alunno, MD, is consultant rheuma-tologist and PhD candidate at the Rheumatology Unit, University of Perugia, Italy. Her main research interest is the role of T lymphocyte subsets in the pathogen-esis of connective tissue diseases.

Alessia Alunno

In recent years, a variety of novel T lymphocyte subsets characterized by peculiar phenotipic features and the secretion of specific cytokines have been identified. Indeed, their potential role in the pathogenesis of autoimmune diseases is gaining scientific interest. Roeleveld et al [THU0495] reported that the onset and progression of arthritis in IL-1Ra-deficient mice (that develop spontaneous arthritis) is dependent on IL-22, a dual cytokine with both proinflammatory and anti-inflam-matory properties secreted by Th17 cells. IL-23, a heterodimeric cytokine consisting of an IL-23p19 and an IL-12p40 subunit, mainly produced by dendritic cells, favors the expansion and stabilization of the Th17 phenotype. Yeremenko et al [OP0107] provided evidence that IL-23/IL-17-related cytokines including CD21L, IL-23, IL-17F, IL-21 and IL-22 are associ-ated with a specific histological pattern of RA synovitis characterized by ecto-pic lymphoid structures. In this setting Penatti et al [OP0224] reported that, Th17 cells accumulate in synovial tissues of RA patients and IL-17 both in serum and synovial fluid correlate with disease activ-ity. They also demonstrated that follicular T helper (Thf) cells, an IL-21 producing T cell subpopulation promoting B-cell maturation, inducing class switching and affinity selection and eventually leading to ectopic lymphoneogenesis, accumulate in rheumatoid synovium.

IL-21 expression can be modulated by sex hormones, as reported by Lee et al [THU0532] demonstrating that in systemic lupus erythematosus (SLE) estrogens upregulate IL-21 expression of CD4+ T cells via MAPK dependent pathways eventually leading to increased antibody production by B cells. These observations may contribute to shed some additional light on the gender differences observed in this disease.In SLE pathogenesis, the imbalance be-tween Th17 and regulatory T cells (Treg) is a hot topic. Jakiela et al. [AB0029] reported that this may be at least partially explained by the fact that in SLE associ-ated lymphopenia affects primarily Treg and Th1, but not Th17 cells leading to a relative deficiency in Treg suppressive function and consequently to an in-creased proinflammatory response during active disease.An intriguing attempt to target Th17 cells was presented by Al-Mossawi et al [THU0503] using a small molecule inhibiting RORγt, the peculiar transcrip-tion factor of Th17 cells, in vitro. A selec-tive depletion of rheumatoid arthritis and psoriatic arthritis CD4+Th17 cells was observes along with an inhibition of IL-17A release. These promising findings may provide the basis for futher investigation of this in experimental models and possibly in clinical trials.



RA IEpidemiology, clinics and non biologics

Elena Nikiphorou, MBBS/BSc, MRCP, MD, is a Rheumatology Research Fellow at the University of London & University of Hertfordshire, United King-dom. Her main research interest focuses on RA outcomes, comorbidities and the impact of modern treatments.

Elena Nikiphorou

Van Nies et al. [OP0035] explored RA symptom duration at treatment-onset in relation to achieving DMARD-free sus-tained remission in the Leiden Early Arthri-tis Clinic and ESPOIR. A non-linear rela-tionship was observed between the two with the data suggesting that the window of opportunity starts to close 13-19 weeks after symptom onset. This appeared to occur earlier in ACPA-positive RA (14.6 weeks) compared to ACPA-negative RA (18.9 weeks).Norton et al. [OP0127] in a study based on two of the largest and longest RA in-ception cohorts in the UK (ERAS & ERAN) demonstrated that different rates of HAQ progression exist for different treatment profiles. Patients with higher average levels of disease activity over the course of disease experienced faster rates of progression. Individuals with persistently low disease activity treated with DMARDS experienced rates of HAQ progression similar to those observed as a result of ageing in the general population.Sundström et al. [OP0195] investigated the relationship between consumption of sodium chloride, smoking and seroposi-tivity among individuals with RA in the Epi-demiological Investigation of Rheumatoid Arthritis (EIRA) cohort study. High con-sumption of sodium in current smokers was associated with an increased risk for ACPA positivity compared with smokers with low sodium intake (OR=2.21, 95% CI

1.26-3.89). One possibility suggested is that smoking may be involved in triggering of Th17 activation of pathogenic impor-tance in ACPA positive RA.Mantel et al. [OP0168] in a study of 39065 individuals with prevalent RA between 2005 and 2009 identified using the Swed-ish nationwide patient registry, found that the increased risk of ischaemic stroke in RA is not entirely explained by traditional risk factors, suggesting additional mecha-nisms at play. There was no difference in neither the clinical presentation of isch-aemic stroke nor the case-fatality after ischaemic stroke between RA patients and general population.Morel et al. [SAT0156] found that the scores of a self-administered question-naire, FLARE-RA, were significantly cor-related with RA disease activity over the 3-month period preceding the visit to the rheumatologist. The questionnaire could be used in monitoring disease activity between rheumatologist consultations and identify patients whose appoint-ment should be anticipated or treatment revised. Radner et al. [THU0448] in a survey developed and sent to 29 European RA registers and clinical cohorts found increased heterogeneity in the mode of data collection. They propose that data collection across Europe is better harmo-nized to facilitate future data sharing and combined analytical approaches.


Mislav Radić, MD, PhD, is an Assistant Professor of Internal Medi-cine and he is currently working in the Division of Rheumatology and Clini-cal Immunology, University Hospital Split, Croatia. His scientific and clinical inter-ests are systemic sclerosis, osteoarthritis, vasculitis, epidemiology and imaging tools in rheumatology.


RA IIAnti-TNF and B cell therapies

Russka Mislav Radić

Treatment options in rheumatoid arthritis (RA) are improving constantly, however, the safety of such treatment and treatment options during pregnancy are still objec-tive of numerous investigations. Biological therapy has brought a revolution in the RA treatment. Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF approved in 45 countries for the treatment of RA and/or Crohn’s disease; it was recently ap-proved by the EMA for psoriatic arthritis and axial spondyloarthritis. Analysis of pregnancy data from the UCB Pharma global safety database through 06 March 2012 has been published previously.Clowse et al. [OP0067] have provided an updated analysis of pregnancy outcomes in rheumatic patients after CZP exposure, with a focus on RA, by including new reports and pregnancies that were still ongoing at the time of the last retrospec-tive analysis. The final conclusion of this updated analysis of pregnancy outcomes after exposure to CZP supports previous reports suggesting no apparent impact of maternal CZP exposure on pregnancy outcomes. However, additional prospec-tive data are required to fully evaluate the safety and tolerability of CZP in preg-nancy. Biologics such as anti-TNF agents have been shown to rapidly induce remission in early RA, which may improve the likelihood of long-term treatment suc-cess. Current EULAR guidelines suggest consideration of biologic withdrawal after achievement of a good clinical state, but

few studies have explored which patients are the best candidates for therapy reduc-tion or withdrawal. Emery et al. [OP0039] examined the influ-ence of demographic and disease char-acteristics and early treatment response on the achievement of sustained remis-sion in patients with early RA in the PRIZE study. The final conclusion of this study is that early onset of response to induction therapy with etanercept plus MTX predict-ed sustained remission with a reduced-dose combination maintenance regimen. These findings are clinically relevant as prompt recognition of patients unlikely to achieve response targets may allow for more timely adjustments in treatment and ultimately better long-term outcomes. In Europe, rituximab (RTX), an anti-CD20 monoclonal antibody, is reserved for RA patients with who have failed initial anti-TNF therapy. There is a concern over whether B-cell depletion and potential resultant hypogammaglobulinaemia may result in an increased risk of serious infec-tions. Silva-Fernandez et al. [OP0029] have performed the study which aim was to determine if RTX influences the risk of serious infections when used in routine clinical practice. Finally, patients receiving RTX after one anti-TNF failure do not ap-pear to have an increased risk of serious infections during the 1st year of treatment compared to patients receiving a 2nd anti-TNF.



RA IIIOther biologics and new drugs beyond biologics

Katerina Chatzidionysiou, MD, is a Rheumatology Fellow at Karolinska Univ-eristy Hospital (Stockholm). Her main research focus is biologic treatment of rheu-matoid arthritis.

Katerina Chatzidionysiou

Genovese et al [OP0028] presented a phase 3 trial of sarilumab in RA patients who were inadequate responders to methotrexate. Sarilumab is a fully-human monoclonal antibody against the IL-6 receptor.1197 patients with active RA were randomized to sarilumab 150mg, sarilum-ab 200mg or placebo, all in combination with MTX. Both sarilumab groups showed statistically significant improvements compared to placebo in three co-primary endpoints, ACR20 responses at week 24, improvement in physical function at week 16 and inhibition of structural damage at week 52. ACR20 was achieved by 58%, 66% and 33% in the 150mg, 200mg and placebo groups, respectively. 13% of patients in the 150mg, 15% in the 200mg and 3% in the placebo group achieved ACR70 response. Infections were the most frequently reported adverse events. Sarilumab was associated with a dose-dependent decrease in mean neutrophil counts. Itolizumab is a humanized IgG1 monoclonal antibody that selectively targets CD-6, which is involved in co-stimulation, adhesion, and maturation of T cells. Chopra et al [OP0027] presented a phase 2, randomized, placebo controlled trial where the efficacy and safety of itoli-zumab in combination with methotrexate in RA was assessed. A total of 70 patients

were randomized into 3 different dose ac-tive treatment groups (0.2, 0.4 and 0.8mg/kg) and placebo. Itolizumab patients had higher ACR20 response rates at 12 weeks (50%, 60%, and 40%) compared to 30% in placebo group. Overall, at 12 weeks, 58.3% of the itolizumab patients achieved EULAR moderate or good response vs. 20% in MTX-only group. Itolizumab was well tolerated with the majority of AEs being mild or moderate. Van Vollenhoven et al [OP0151] presented the results of a phase 2 trial of decernotinib, an oral selective Janus Kinase 3 inhibitor in combination with methotrexate in RA. At week 24, 60.6% of patients given 100mg decernotinib had achieved ACR20 as had 61.1% of those receiving 150mg, com-pared with 16.9% of those given placebo (P<0.001 for both). For the four dos-ing regimens (100 mg per day, 150 mg per day, 200 mg per day, 100 mg twice daily), ACR50 responses at 6 months were seen in 38%, 38.9%, 40.3%, and 47.2%, respectively, compared with 7% of placebo recipients (P<0.001 for all), Re-mission was achieved by only 5.6% of placebo patients compared with 21.1% for the 100-mg-per-day group (P<0.01) and by 29.2%, 27.8%, and 31.9% of the other three groups (P<0.001 for all).


Russka Shumnalieva, MD, currently works as a rheumatology fellow and PhD candidate at the Medi-cal University, Sofia (Bul-garia). Her major research work focuses on epigenetic changes and microRNA expression in rheumatic diseases. She is the coun-try liaison for EMEUNET in Bulgaria.


PSORIATIC ARTHRITIS

Russka Shumnalieva

The advances in the field of genetics, immunology and molecular biology have improved the understanding of underlying disease mechanisms in psoriatic arthritis (PsA). As the early and intensive treat-ment in PsA in the clinical practice has been proven to lead to an improved clini-cal and radiographic outcome, studies and reports about new treatment strate-gies in PsA are of great interest. Apremilast (APR) is a new oral – phos-phodiesterase 4 inhibitor that works intra-cellularly to regulate the inflammatory me-diators. Several studies regarding its use in patients with PsA have been reported at EULAR congress. PALACE 1, 2 and 3 trails compared the efficacy/safety of APR with placebo in patients with active PsA despite prior conventional DMARDs and/or biologics. Kavanaugh et al. [OP0078] reported clinically meaningful improve-ment on disease activity though 52 weeks despite baseline body mass index and body weight. No dose adjustment is re-quired according to Schett et al. from the same study group [AB0746]. PALACE 4 compared the efficacy/safety of APR with placebo in DMARDs-naïve patients with active PsA. Edwards et al. [SAT0389] re-ported that among patients continuously treated with APR sustained improvements in both enthesitis and dactylitis were observed through the whole study period. The treatment was associated with clini-cally meaningful long-term improvement in physical function in this subset of pa-tients according to Wells et al. [SAT0382]. The effect of Ustekinumab (UST), an IL-12/23 p40 inhibitor, on inhibiting ra-

diographic progression in patients with active PsA in the PSUMMIT1 and PSUM-MIT 2 trails was analysed by McInnes et al. [OP0079]. Radiographs of hands and feet were evaluated for erosions and joint space narrowing (JSN) using PsA modified van der Heijde-Sharp (vdH-S) method. Analysis based on a pre-speci-fied integrated data analysis using data combined from both studies showed that radiographic progression is inhibited by UST at week 24.Using next generation sequencing Mus-ters et al. [AB0021] found that identical expanded T cell clones were present in the synovial tissue of different joints but were not fully represented in paired peripheral blood and synovial fluid samples which showed that pathogenic T-cell clones focuses on ST rather than PS and SF. Clones with a frequency of ≥0.5% were arbitrarily considered to be expanded.Based on a population-based cohort study with 3161 PsA patients Kibari et al. [SAT0378] described high prevalence of cardiovascular co-morbidities in patients with PsA and recommended close moni-toring and treatment of risk factors. The spectrum of cardiac involvement included not only ischemic heart disease, carotid artery disease, peripheral vascular dis-ease, but also increased risk of cardio-myopathies, congestive heart failure and valvular heart disease. Papagoras et al. [AB0743] found high prevalence of metabolic syndrome in PsA patients and connected this with the low HDL levels found in this subtype of patients.



AXIAL SPONDYLOARTHRITIS

Paul Studenic, MD, is a medial resident and clinical research fellow at the division of rheumatol-ogy of the Medical Uni-versity Vienna in Austria, working on his PhD. His main interests are rheu-matoid arthritis, patient reported outcomes, predic-tors of disease activity and biomarkers. He is currently engaged in the EMEUNET Website Subgroup.

Paul Studenic

Mandl et al. [FRI0127] presented the new recommendations on the use of imaging in spondylarthritis (SpA) in clinical prac-tice. An expert group formulated research questions, which were then addressed by three systemic literature reviews, that in the end included 158 articles to provide evidence. 10 recommendations were elaborated, the most important are: X-ray of sacroiliac (SI) joints is the method of first choice to diagnose SpA and if the clinical diagnosis cannot be established an MRI of the Si joints is recommended. For peripheral SpA US or MRI can be used to detect enthesitis. MRI using STIR sequences provides additional information in monitoring of SpA activity. Bone marrow edema may be used as predictor for good response to anti-TNF treatment.Cypers et al. [OP0159] demonstrated the role of microscopic gut inflammation as potential predictor of disease severity. 63 patients of the GIANT cohort, who had iliocolonoscopy and a follow-up since the time of diagnosis of either an axial SpA or a peripheral SpA were included in this study. Microscopic gut inflamma-tion was found in 32 patients. A TNF-inhibitor treatment was initiated in 57% of the patients with chronic microscopic gut inflammation and 55% in the patients with acute microscopic gut inflammation. The authors showed that anti-TNFi treatment was likelier to be received by patients with microscopic gut inflammation , elevated CRP or ASDAS, thus gut inflammation

might be utilized as prognostic factor.Molto et al. [AB0947] investigated the psychometric properties of plain x-ray evaluation of the SI joints in 29 ankylosing spondylitis (AS) patients (in terms of the modified New York criteria) and 48 con-trols. The two readers were blinded when scoring the pelvic x-ray by the modified New York criteria, the assessment of dam-age was performed by only one reader. Cohen’s κ for intra- and inter-reader agreement were 0.4 (0.19-0.99) and 0.36 (0.09-0.63) respectively. The sensitivity and specificity for detection of structural damage were 0.76 (0.58-0.88) and 0.84 (0.71-0.91). Even though the agreement was modest the specificity for evaluation of structural damage was good.Ramiro et al. [OP0262] assessed the relationship between occupational activity and radiographic damage in patients with AS. Patients were followed over 12 years with biannual assessments and x-rays were scored by mSASS. Blue vs white collar, education and baseline monthly income, as well as smoking were used in a GEE model. Personal income and occupational activity had a significant influence on the relationship between disease activity scored by ASDAS and radiographic progression, also when adjusted for smoking habits. This leads to the conclusion, that the effects of disease activity on radiographic damage may be amplified by physical occupation.



SLE & APS

João Madruga Dias, MD, is a Rheumatologist at Santa Maria University Hospital (Portugal) with a special interest in inflam-matory rheumatic diseases in pregnancy, seronegative spondyloarthropathies, musculoskeletal-ultrasound and arthroscopy. He trained arthroscopy in Saint Vincent’s University Hos-pital, University College of Dublin.

João Madruga Dias

Systemic Lupus Erythematosus (SLE) ty-pically affects women of childbearing age and can be associated with significant ma-ternal and fetal morbidity. Pregnant women were excluded from belimumab clinical trials and treatment was discontinued if a pregnancy occurred. Nevertheless Powell and colleagues [OP0041] collected preg-nancy outcomes when a pregnancy was identified. Their work showed a lower fre-quency of fetal loss in subjects treated with belimumab (27%; 18/66) compared to the placebo group (50%; 3/6). They concluded that total fetal loss in belimumab-treated subjects was similar to background esti-mates in SLE patients (κ25%). Although data remain limited, this study may reveal a potential treatment option for SLE patients who are contemplating pregnancy or are pregnant.Atacicept is a fusion protein that inhibits B-cell stimulating factors BLyS and APRIL. Gordon and colleagues [OP0044] exami-ned the efficacy of atacicept in preventing SLE flares. Patients reaching BILAG C or D at weeks 10 and 12 were randomized to receive placebo, atacicept 75mg (A75) or 150mg (A150) twice weekly for every 4 weeks, then weekly for 48 weeks. A lower proportion of subjects with ≥1 BILAG system A or B flare was observed in A150, A75, vs placebo: 20.8%, 38.9% vs 41.6%. The proportion of subjects with a BILAG flare in each organ system was reduced in A150 versus placebo, with the exception of vasculitis. A post-hoc analysis revealed severe SELENA-SLEDAI flare during treat-ment in 19%, 11%, and 13% of patients for placebo, A75, and A150, respectively. Albeit promising, results warrant further studies to assess the safety and efficacy.Neuropsychiatric manifestations in sys-temic lupus erythematosus (NPSLE) are serious complications of the disease.

Hirohata and colleagues [OP0215] ex-plored the association of cerebrospinal fluid (CSF) anti-Sm with various subsets of NPSLE. Paired serum and CSF specimens were obtained from 72 NPSLE patients: 49 diffuse NPSLE, 23 neurological syndromes/peripheral neuropathy (focal NPSLE) and 22 controls (non-SLE neurological disea-ses). Anti-Sm and anti-RNP in CSF and sera were elevated in NPSLE compared with non-SLE controls. Among NPSLE, CSF anti-Sm, but not CSF anti-RNP, were significantly elevated in acute confusio-nal state (ACS) compared with non-ACS diffuse NPSLE or focal NPSLE. Additionally, monoclonal anti-Sm bound to the surface of neuroblastoma cell lines. These results indicate that anti-Sm are constituents of anti-neuronal antibodies and that CSF an-ti-Sm plays an important role in the patho-genesis of ACS.The proteasome inhibitor bortezomib, approved for the therapy of multiple my-eloma, depletes plasma cells (PCs) and ameliorates nephritis in SLE mouse mod-els. Alexander and colleagues [FRI0394] included 12 patients with active SLE in a prospective multicentre cohort study. The disease activity (SELENA-SLEDAI) signifi-cantly decreased upon induction therapy with bortezomib and remained stable for the following 3 months under maintenance therapies. Treatment-related adverse events were mild or moderate. Upon bort-ezomib treatment, peripheral blood PCs were strongly decreased, whereas circulat-ing B cells remained unaffected. PC num-bers significantly increased in-between cycles. Bortezomib may represent an effective treatment option with low toxicity in refractory SLE patients, inducing short-term remissions but requiring maintenance treatment.



OTHER CONNECTIVE TISSUE DISEASES

Barbara Ruaro, MD, currently works at the Research Laboratory and Academic Division of Clini-cal Rheumatology, Depart-ment of Internal Medicine, University of Genova, Italy. Her areas of interest are systemic sclerosis, ultraso-nography, peripheral blood perfusion, treatment strate-gies and rehabilitation.

Barbara Ruaro

Nowadays, the gold standard technique to evaluate the pulmonary fibrosis is high resolution CT (HRTC). However, it is costly and exposes the patient to radiological risk. Karalilova et al. [FRI0497] carried out a very interesting study showing a correlation between lung ultrasound and HRCT, in particular it demonstrates that the presence of B-lines at lung ultrasound correlates with lung interstitial disease at HRCT. Therefore, ultrasound may be adopted as a standard screening tool for pulmonary involvement followed HRCT if indicated. It is common practice to use FVC% in clinical trials as primary outcome to evaluate treatment response. However, it is a single measure for such a complex situation. The objective of Volkmann et al’ s study [OP0275] was to develop a compos-ite outcome measure to assess treatment response in systemic sclerosis patients with interstitial lung disease. They evalu-ated two groups of patients, one treated with cyclophosphamide and the other with placebo to determine which had a signifi-cant treatment effect at 12 months: FVC% predicted, TLC% predicted, computer-based quantitative lung fibrosis in the zone of maximum fibrosis, thoracic high-resolu-tion computed tomography scan scores, transitional dyspnea index and the visual analogue scale for breathing. The compos-ite outcome, which included quantitative lung fibrosis in the zone of maximum fibro-sis and the transitional dyspnea index, was in favour using cyclophosphamide for the treatment of interstitial lung disease in SSc patients (SSc-ILD). Moreover, the treat-ment effect observed using the composite outcome was more significant than the that observed using FVC % predicted. Sanges et al. [OP0096] reported that there was a correlation between the initial 6MWT total

distance and the hemodynamic param-eters of PAH severity, especially the mean pulmonary arterial pressure in systemic sclerosis patients with pulmonary hyper-tension without interstitial lung disease. Not only is this test important to assesses the severity of the PAH in this population but, there are most likely to be other factors in-volved in the 6MWT total distance. The aim of Lazzaroni et al.’s study [OP0230] was to evaluate the maternal/neonatal outcome and disease course before, during and after pregnancy in patients with systemic vasculitis. They concluded that although systemic vasculitis patients may have successful pregnancies, with 85.9% of live births 85.9%, there is an increased risk of preterm delivery. Therefore, strict control of these patients was recommended through-out their pregnancy by a multi-disciplinary specialist team to evaluate the risk of severe complications. Hofauer [THU0002] carried out a study to evaluate whether the modern ultrasound techniques could add further information to B-mode ultrasonog-raphy in the assessment of parotid and submandibular gland involvement in pa-tients with a suspicion of primary Sjogren’s Syndrome. They concluded that, although B-mode ultrasonography is useful for the visualization and subjective assessment of structural glandular alterations, acoustic radiation force impulse imaging allows for the objective measurement of glandular stiffness and, therefore, might be consid-ered in the diagnostic algorithm of primary Sjogren’s Syndrome. Go et al. [OP0094] reported a statistically significant survival benefit of early cyclosporine administra-tion in patients with dermatomyositis-as-sociated ILD providing the basis for future randomized controlled studies.



IMAGING

Christian Dejaco, MD, PhD is a consultant and Assistant Professor at the Medical University Graz. His main research interests are the value of ultrasound in rheumatol-ogy, clinical research on polymyalgia rheumatica and translational research on T lymphocyte senescence in rheumatology.

Christian Dejaco

Ng et al. [OP0054] investigated 54 pa-tients with early Rheumatoid Arthritis (RA) (<1year) to compare Power Doppler (PD) findings with histology at the clinically most affected joints. Ultrasound guided biopsies were taken before and 6 months after disease modifying anti-rheumatic drug (DMARD) treatment. PD scores and histological markers of inflammation correlated well and the authors observed a reduction of inflammatory activity by sonography and histology after therapy.Croft et al. [OP0056] performed a ret-rospective analysis of 87 patients with suspected giant cell arteritis (GCA) to compare the diagnostic value of sonogra-phy versus histology of temporal arter-ies. A clinical diagnosis of GCA after 3 months served as the golden standard. The authors reported that sonography had a higher sensitivity (81% vs. 53%) and comparable specificity (98% vs. 100%) to biopsy. Haugen et al. [OP0062] presented the results of a prospective, long term follow-up study of patients with hand osteoarthri-tis (OA) out of the Oslo cohort. Magnetic resonance imaging (MRI) verified bone marrow edema (BME) [odds ratio (OR) 2.1] and synovitis (OR 1.7) at baseline were associated with radiographic pro-gression after 5 years.

Inanc et al. [FRI0236] observed in a longi-tudinal follow-up study of 43 RA patients undergoing anti-TNFκ therapy that a higher PD score at baseline was associ-ated with a lower likelihood for a EULAR response at 3 months. A new ultrasound composite score for Psoriatic Artritis (PsA) patients was proposed by Ficjan et al. [SAT0170]. In a prospective study with visits at baseline and 6 months, they investigated a total of 68 joints and 14 entheses by means of so-nography. A bilateral (including 22 joints and 4 entheses) and unilateral (13 joints, 2 entheses) score were produced reveal-ing moderate to good discriminatory, internal and external validity, reliability and feasibility.Baraliakos et al. [OP 0049] compared MRI, 18F-FDG positron emission tomog-raphy (PET)/MRI and computer tomog-raphy (CT) scans in 13 active ankylosing spondylitis (AS) patients. They observed that vertebral quadrants (VQ) with fat deposition were more likely to be PET positive than VQ with BME. In addition, one third of syndesmophtes revealed 18F-FDG signals indicating that tracer uptake may not only reflect inflammation but also increased bone metabolism.


CRYSTAL ARTHROPATHIES

Lucia Silva, MD, MSc, is a consultant rheumatologist at Com-plexo Hospitalario Univer-sitario de Ferrol in Spain. She is currently working as a clinical research fellow at the Arthritis Research UK Centre for Epidemiology of the University of Manches-ter, UK.

Lucia Silva


Gout does not affect both sexes in the same way. Harrold et al [OP0136] char-acterized the differences of gout between women and men in terms of predisposing factors, comorbid conditions and treat-ments. Patients included in this analysis were participants of the Consortium of Rheumatology Researchers of North America (CORRONA) registry. Women were older, more commonly nonwhite, heavier and more commonly had hy-pertension, diabetes and renal disease. Women had a shorter duration of gout and were less likely to have a crystal-proven diagnosis. Medication risk factors for gout (e.g., diuretics), were more com-mon in women, while dietary risk factors were more frequent in men (intake of beer, hard liquor, beef and pork). Women and men had similar clinical features in terms of acute gout presentation (podagra, oligoarthritis, etc.) when initially diagnosed with gout, and gouty arthritis (tophi, joint deformity), as well as average number of flares, but women reported more frequent disability. Women were more likely to have contraindications to treatment with NSAIDs or colchicine. Physicians should be aware of these differences, in order to tailor their treatment recommendations, to ensure all patients achieve optimal disease control.Ultrasonography is being increasingly used for the management of gout. Otta-

viani et al [OP0008] studied the ability of US to detect the disappearance of urate deposits in the knee and first metatarso-phalangeal joint of 16 gouty patients receiving urate-lowering therapy. After 6 months of treatment, serum uric acid (SUA) levels decreased in 12 patients. The follow-up US examination showed a good correlation with the SUA levels (k=0.875). Therefore, US examination is a sensitive tool to detect improvement in joint uric acid deposits in gouty patients.Filippou [SAT0510] compared the util-ity of ultrasonography and synovial fluid analysis for the diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease using the microscopic analysis of the meniscus and cartilage extracted during surgery as the gold standard. US demonstrated a sensitivity of 95% with PPV = 0.91 and specificity of 81% and a NPV = 0.90 while respective values for synovial fluid microscopic analysis were 73% with PPV of 1 and 100% with NPV of 0.69. The authors believe that due to its non-invasive nature, the high specificity and specificity the capability to address differential diagnosis, US should be the first exam to be performed when CPPD disease is suspected. As this study dem-onstrates, the presence of CPP crystals in the synovial fluid, definitely confirms the diagnosis but a negative microscopic exam does not exclude it.



OSTEOARTHRITIS & OSTEOPOROSIS

Ida K. Haugen, MD, PhD, is a Rheumatolo-gy fellow and post-doctoral researcher in the Depart-ment of Rheumatology at Diakonhjemmet Hospital, Oslo, Norway. Her main research interest is hand osteoarthritis epidemiology and imaging.

Ida Haugen

Using data from the NEO study in the Netherlands, Wisser et al. [OP0144] found significant associations between knee osteoarthritis (OA) and both weight and fat free mass after adjustment for metabolic factors. In hand OA the opposite was ob-served. Significant association was found between hand OA and metabolic syn-drome after adjustment for weight. These findings indicate that mechanical stress seems the most important underlying mechanism in knee OA, whereas systemic processes might contribute most in hand OA alone.In a longitudinal 2.7-years study of 416 old-er adults from the community, Wang et al. [OP0064] showed that suprapatellar pouch effusion was associated with change in cartilage volume, increases in cartilage defects and an increase in bone marrow lesions (BMLs) in the knee. Similar results were found for effusion at posterior femoral recess and subpopliteal recess (except no association to increase in BMLs). The conclusion of their study was that knee joint effusions are associated with knee osteoarthritic structural changes suggest-ing a potential causal relationship. In a population-based study of 319 per-sons with clinical hand osteoarthritis (OA), Magnusson et al. [FRI0577] showed that lower age, more radiographic and inflam-matory features were related both to self-reported hand pain and joint tenderness assessed by a rheumatologist. Interest-ingly, having diabetes was associated with both pain outcomes. Persons with low education and pain at multiple sites re-ported more hand pain. Although the study included a broad range of possible predic-tors of pain, only a small part of the varia-

tion in hand OA pain can be explained.Haugen et al. [OP0062] explored the predictive value of MRI in a 5-year lon-gitudinal study of 74 patients from the Oslo hand osteoarthritis (OA) cohort. The distal and proximal interphalangeal joints were imaged by MRI at baseline, whereas conventional radiographs were obtained at baseline and follow-up. They found that synovitis and bone marrow lesions could significantly predict radiographic progres-sion in the same joint over 5 years. Kortekaas et al. [SAT0431] investigated the relation between inflammatory features as-sessed by ultrasonography and structural damage over a 2.5-year period in 56 hand osteoarthrits (OA) patients. Inflammatory US features (synovial thickening, effusion and power Doppler activity), especially when persistently present at both baseline and 2.5-year follow-up, were independently associated with radiographic progression in hand OA after 2.5 years, indicating a role of inflammation in the aetiology of structural damage in hand OA. Using data from the HOSTAS study (Hand OSTeoArthritis in Secondary care), Liu et al. [SAT0453] stud-ied the associations between MRI features and joint tenderness assessed at clinical examination and self-reported hand pain in patients with hand osteoarthritis (OA). Synovitis and bone marrow lesions (BMLs) on MRI were associated with pain upon palpation. No associations were found between number of joints with MRI features and self-reported hand pain. However, the associations between MRI findings and joint tenderness suggest a role for inflam-mation and subchondral bone processes in the pathogenesis of hand OA.


PAEDIATRIC RHEUMATOLOGY

Walter Alberto Sifuentes Giraldo, MD, is a research associate at the Department of Rheu-matology of the University Hospital Ramon y Cajal, Madrid - Spain. His main research interest focuses on pediatric rheumatol-ogy, spondyloarthritis and biological therapies.

Walter Sifuentes

Recent advances in the management of JIA are a strong argument to the incor-poration of a treat-to-target approach in these patients in order to achieve clini-cal remission (CR) or, at least, minimal disease activity (MDA), both based on JIA activity score (JADAS) (CR < 2, MDA < 3.8). Ruperto et al [OP0181] performed a post hoc analysis of data from a phase 3 clinical trial in polyarticular juvenile idio-pathic arthritis (JIA), and they found that adalimumab, regardless of methotrexate, resulted in a high percentage of patients achieving and sustaining MDA and normal function. Horneff et al [OP0183] assessed CR and MDA upon first biologic in 2111 JIA patients from the German BIKER-registry. Most patients achieved MDA but CR only by a part, and both were more frequent with tocilizumab than adalimumab or etanercept.Canakimumab, an anti-IL1κ monoclonal antibody, has emerged as an effective treatment for systemic JIA with active systemic features, supported by 2 large randomized clinical trials. Wulffraat et al [OP0180] presented the results of the continued canakimumab treatment in systemic JIA patients during the blinded randomized treatment withdrawal part of one of these trials. Patients with active systemic JIA who responded to open la-bel canakimumab treatment 4mg/kg/4wks sc and continued this drug had a signifi-

cant risk reduction of 51% to develop a worsening in pediatric ACR30 compared with placebo, and they also achieved CR on medication and clinical inactive disease more frequently. Safety of cana-kimumab was evaluated in a pharmaco-metric-based analysis in systemic JIA patients treated with a therapeutic dose of this drug by Dumortier et al [OP0182]. They did not find any relationship between average canakinumab exposure and the occurrence of any specific safety events, except for neutropenia, but this was not associated with increased infections. Horneff et al [OP0186] analysed 3467 JIA patients exposed to biological therapies from the BIKER-registry and identified the history of uveitis and etanercept mono-therapy as risk factors for development of uveitis as an adverse event. Methotrex-ate treatment was a protective factor but corticosteroids did not have this effect. The efficacy of tocilizumab en JIA patients with uveitis refractory to immunosuppres-sive and anti-TNF drugs was evaluated in a retrospective study of 6 cases by Sukumaran et al [FRI0559]. Its use was associated with improvement in ocular inflammation, visual acuity, reduction in concomitant immunosuppression, and it was well tolerated in all patients.


ACTIVITIES EULAR 2014, PARIS

EMEUNET MENTOR-MENTEE The Peer Mentoring group was set up to promote discus-sions between mentees and mentors and to facilitate train-ing from mentors.

The EMEUNET mentor-mentee working group (Sibel Aydin, Lucía Silva Fernan-dez, Suzan Verstappen) organized the second EMEUNET mentor-mentee at EULAR in Paris which was a great suc-cess again. Three experts in the field of epidemiology (Professor Angela Zink), basic science (Professor Ian McInnes) and rheumatoid arthritis (Professor Paul Emery) kindly agreed to meet with EMEU-NET members to informally discuss for ex-ample their research or career plans dur-ing a one hour meeting. 100% mentioned that they enjoyed the meeting and would recommend it to other mentees. Some quotes from participants were: “pleasant

atmosphere, nice colleagues in a group with a perfect size (4-5 participants), and brilliant mentor”, “The mentor was very honest and gave useful insights into her career/experiences”, “The experience sharing, open talk, the meeting in informal surrounding was found to be good”. The next mentor-mentee meeting will be at ACR in Boston. Please let us know who you would like to meet ([email protected], [email protected], [email protected]).

Many thanks,Suzan Verstappen

With the EMEUNET network exceed-ing 900 members to date, we set our minds to bringing together the people who make this possible – the country liaisons. So, at this year’s EULAR Congress in Paris, aside from the EMEUNET booth we planned a face-to-face meeting for our country liaisons. The odds were in our favor:

more than 15 countries were repre-sented, together with members of the EMEUNET Steering Committee and Working Group. It was an interactive, lively meeting, where points were raised, experiences were shared and ideas were put forward. Addressing the specific needs of young rheuma-tologists in each country remains our

priority, and, despite huge advances to date, we are not complacent and constantly aim for improvement. With such a dedicated team, the pros-pects are great! We kindly thank all who participated and supported this event! Let this be the first of a long series of productive meetings to come!

SUZANNE VERSTAPPENLeader of the Peer Mentoring Subgroup

THE FIRST EMEUNET COUNTRY LIAISON MEETING


AUGUST 2014

The 6th Ten Topics in Rheumatology SingaporeAugust 2-3, 2014, Singaporewww.msr.my/article.php?aid=301 or www.tentopicsa-sia.com

XV Mediterranean Congress of RheumatologyAugust 28-31, 2014, Istanbul, Turkeywww.romatoloji.org

EFORT Advanced Instructional Course: Hip Pathol-ogy in Young Adults August 28-29, 2014, Bern, Switzerlandwww.efort.org

SEPTEMBER 2014

Polish Society for Rheumatology 22nd Congress 2014September 3-5, 2014, Katowice, Polandhttp://www.symposion.pl/xxii-kongres-ptr/list-pow-italny

9th EULAR On-line CourseStart: 8 September 2014http://www.eular.org/myUploadData/files/Web%20overview%20modules_2012%20(2).pdf

33rd Conference of the European Bone and Joint Infection Society (EBJIS 2014) September 11-13, 2014, Utrecht, Netherlands. www.ebjis2014.org

6th EULAR Course on Capillaroscopy September 11-13, 2014, Genoa, Italyhttp://www.eular.org/index.cfm?framePage=/course_description_capillaroscopy.cfm

Update in Musculoskeletal Imaging September 11-13, 2014, Bruges, Belgiumhttp://www.update-medical-imaging.be/edition2014/default.html

1st EULAR / PReS On-line Course in Paediatric Rheu-matologyStart: 15 September 2014http://www.eular.org/index.cfm?framePage=/edu_on-line_course_paediatric.cfm

HipToulouse 2014September 17-19, 2014, Toulouse, Francewww.hipnews.org

42nd Congress of the German Society of Rheumato-logy September 17-20, 2014, Düsseldorf, Germany http://www.dgrh-kongress.de

XXI Congress of Pediatric Rheumatology European SocietySeptember 17-20, 2014, Belgrade, Serbiawww.pres2014.org

European Society for Surgery of the Shoulder and Elbow (ESSSE): 25th Congress September 17-20, 2014, Turkey, Istanbulwww.secec.org

Comorbidities in Rheumatology September 15, 2014, London, United Kingdomhttp://events.rcplondon.ac.uk/details.aspx?e=3139

31st AGA Congress, Arthroscopy Association of Ger-man Speaking Countries AGA AAGSC September 18-20, 2014, Innsbruck, Austria.www.orthopaedicseminar.com

16th International Conference on Behcet’s Disease September 18-20, 2014, Paris, France. www.congres-medicalcongress.com

21st European Pediatric Rheumatology Congress (PReS 2014) September 18-21, 2014. Belgrade, Serbiawww.pres2014.org

Rheumatology and Critical Care - 5-Night Mediterra-nean Cruise Conference September 18-23, 2014, Barcelona, Spainhttp://www.continuingeducation.net/coursedescrip-tion.php?topic=Rheumatology_Critical_Care_Medi-cine_CME_Mediterranean_Cruise_September_2014

Society for Arthroscopy and Joint Surgery Annual CongressSeptember 18-20, 2014, Innsbruck, Austria. www.agakongress.info/index.html

EDUCATIONAL EVENTS AUGUST – OCTOBER 2014

EDUCATIONAL EVENTS


35th Scandinavian Congress of RheumatologySeptember 20-23, 2014 Stockholm, Sweden. www.scr2014.se

6th EULAR On-line Course on CTD Start: 22 September 2014http://www.eular.org/myUploadData/files/CTD%20web%20overview%20modules_2012%20(2).pdf

4th EULAR On-line Course on SSc Start: 22 September 2014 http://www.eular.org/myUploadData/files/SSc%20web%20overview%20modules_2012.pdf

8th International Conference on Reproduction, Preg-nancy and the Rheumatic DiseasesSeptember 25-27, 2014, Trondheim, Norwayhttp://www.rheumapreg2014.org/doku.php

3rd EULAR On-line Course on US Start: 29 September 2014http://www.eular.org/myUploadData/files/MSUS%20Module%20Planner.pdf

Musculoskeletal II - Erasmus Course on Magnetic Resonance Imaging Module September 29 - October 3, 2014, Porto, Portugalhttp://www.emricourse.org/ms2_2014.html

OCTOBER 2014

Eurospine 2014October 1-3, 2014, Lyon, France. www.eurospine.org

Naples International Shoulder Conference October 2-3, 2014, Naples, Italy. www.nisc.it/home.asp

Bone Densitometry Principles and Procedures October 4-5, 2014, Houston, Texas, USA. www.aheconline.com

International Association for the Study of Pain (IASP): 15th World Congress on Pain October 6–11, 2014, Buenos Aires, Argentina. www.iasp–pain.org

European Hip Society CongressOctober 9-11, 2014, Stockholm, Sweden. www.ehs2014.org

15th EULAR Postgraduate CourseOctober 12-15 2014, Prague, Czech Republichttp://www.eular.org/myUploadData/files/com-plete%20preliminary%20programme%20v5%202014.pdf

International Skeletal Society 41st Annual Meeting and Musculoskeletal Imaging Course October 15-18, 2014, Edinburgh, United Kingdomhttp://www.internationalskeletalsociety.com/Meet-ings/Annual-Meeting/Annual41st/General-Meeting-Information.aspx

The Young Arthritic Knee October 16-18, 2014, Lyon, France.www.lyon-genou.com

9th International Conference on Spondyloarthropa-thies October 23-25, 2014, Gent, Belgium. www.spa-congress.org, www.medicongress.com

EDUCATIONAL EVENTS AUGUST – OCTOBER 2014


EMEUNET Impressions EULAR 2014


More information about EMEUNET can be found on http://emeunet.eular.org.

You can also reach us through the following email: [email protected]

EMEUNET Impressions EULAR 2014

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EDITION JULY 2014 EULAR 2014 PARIS...T helper (Thf) cells, an IL-21 producing T cell subpopulation promoting B-cell maturation, inducing class switching and affinity selection and