the emerging eular network 2014-12 acr.pdfthe emerging eular network edition december 2014 acr 2014...

THE EMERGING EULAR NETWORK

EDITION DECEMBER 2014

ACR 2014 BOSTON Oral presentations, Posters and Mentor-Mentee Programme EMEUNET AT THE NATIONAL CONGRESSES: •  ITALIAN CONGRESS OF RHEUMATOLOGY •  SLOVENIAN CONGRESS OF RHEUMATOLOGY •  DUTCH CONGRESS OF RHEUMATOLOGY •  IRISH CONGRESS OF RHEUMATOLOGY •  POLISH CONGRESS OF RHEUMATOLOGY

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DIRECTORY

EDITORIAL

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Dear young rheumatologists and researchers in rheumatology, we are pleased to introduce you this new issue of EMEUNEWS. The ACR 2014 Congress was a great scientific event and in this issue we provide 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. The ACR Congress was also an opportunity to meet and have fun! As last year, a social event to enjoy together Boston’s nightlife was organized and it was a great success. Finally, the current Newsletter also contains reports on the promotion of EMEUNET at National Congresses around Europe and a calendar of some upcoming educational events. For those of you who still don’t know, EMEUNET members can now stay in touch also via Facebook and Twitter and the pages are constantly growing with information and pictures. 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 EMEUNET 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 contributions for future issues. We wish you relaxing and pleasant Christmas holidays and a very happy New Year. Alessia, Russka, Barbara, Mislav and Xenofon, on behalf of the Newsletter Subgroup

ACR 2014: ORAL PRESENTATIONS & POSTERS 3 Basic Research I and II RA I RA II RA III Psoriatic Arthritis Axial Spondyloarthritis SLE & APS Other connective tissue diseases Imaging Metabolic & Crystal Arthropathies Osteoarthritis & Osteoporosis Pediatric Rheumatology MENTOR-MENTEE PROGRAMME DURING ACR 2014 16 EMEUNET AT THE NATIONAL CONGRESSES 17 WHY BECOME AN EMEUNET MEMBER? 21

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ORAL PRESENTATIONS & POSTERS ACR 2014, BOSTON

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Caroline Ospelt MD, PhD works as postdoctoral fellow in the Center of Experimental Rheumatology in Zurich, Switzerland since 2003. Her research focuses on epigenetic changes, microRNA expression and innate immune pathways in synovial fibroblasts of rheumatoid arthritis patients.

BASIC RESEARCH I AND II Caroline Ospelt, Mary Canavan, Mislav Radic

and Alessia Alunno

Bouta et al (325) presented a possible new treatment approach for RA. Since they could previously show that in the TNF transgenic mouse model of arthritis lymphatic flow from inflamed tissues is blocked, they tried to open lymphatic vessels by using the PDE5 inhibitor tadalafil. Arthritic mice treated with tadalafil had a substantial increase in lymphatic transport resulting in increased volume of popliteal lymph nodes. In parallel, inflammation as measured by power Doppler US and knee synovial volume decreased in treated mice, pointing to a beneficial effect of pharmacological increase of lymphatic flow in arthritis. Qu et al (1202) found an interesting mechanism how type I interferon influences miR-146a levels in SLE. Previously, it could be shown that miR-146a is a critical negative regulator of inflammation, and miR-146a levels were found to be decreased in peripheral blood cells of patients with SLE. In their poster the authors not only show that IFN downregulated levels of miR-146a post transcriptionally in a monocytic cell line, but they also found that this was mediated by MCPIP1, a molecule that is known to antagonize the function of the microRNA processing enzyme DICER1. MCPIP1 was upregulated after IFN stimulation and in peripheral blood of SLE patients and thereby might be a master regulator of miR expression in SLE.

Carey et al (OP 1888) presented interesting data on the regulatory properties surrounding osteoclast differentiation. Although it has previously been noted that transcription factors such as PU.1, MITF, NFATc1, and c-Fos are involved in osteoclast differentiation, the transcriptional regulatory processes surrounding these cells has not been extensively explored. This group examined the target genes of MITF & PU.1 in myeloid precursors and osteoclasts. Microarray analysis was used to identify changes in target gene expression over the course of differentiation. 1000 genes were identified as being regulated jointly by MITF and PU.1 in developing osteoclasts and EOMES was identified as a novel PU.1 copartner necessary for PU.1 transcription. Interestingly inhibition of PU.1 or EOMES in osteoclasts or their myeloid precursor resulted in highly deficient osteoclast differentiation and function in neonatal mice. Stanford et al (OP 2818) investigated the signal transduction pathways involved in the aggressive phenotype of fibroblast like synoviocytes (FLS). Previously protein tyrosine phosphatases (PTPs) were profiled in FLS from RA and OA patients, and the PTPN11 gene, encoding the PTP SHP-2 was found to be overexpressed in RA FLS. To investigate the role of SHP2 in RA, chemical SHP2 inhibitors were used on FLS & migration was assessed. In mice, Ptpn11 was deleted in hematopoietic cells using the Lox/Cre method and disease activity was assessed. Finally in vivo inhibition of SHP2 activity was achieved through the daily administration of a chemical inhibitor to K/BxN arthritis mice. Results showed that FLS migration was reduced upon SHP2 inhibition and global inhibition of SHP2 in the arthritis model resulted in decreased disease severity. Similarly, deletion of SHP-2 in hematopoietic cells led to 50% reduction in arthritis severity.

Mary Canavan is a postdoctoral research fellow within the Translational Rheumatology Group in St Vincents University Hospital Dublin. She has a PhD in Immunology and is interested in the immunopathology of rheumatoid arthritis with a specific interest in inflammatory dendritic cells, synovial fibroblasts and metainflammation.

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Mislav Radić, MD, PhD is Assistant Professor of Internal Medicine and he is currently working in the Division of Rheumatology and Clinical Immunology University Hospital Split, Croatia. His scientific and clinical interests are systemic sclerosis, osteoarthritis, vasculitis, epidemiology and imaging tools in rheumatology.

BASIC RESEARCH I AND II Caroline Ospelt, Mary Canavan, Mislav Radic

and Alessia Alunno

Greisen et al (OP 26) have investigated the potential of synovial fluid mononuclear cells (SFMCs) to develop into functional osteoclasts in vitro. They have provided a new and simple method for generating functional osteoclasts from RA SFMCs. This spontaneous differentiation of osteoclasts from cells of the arthritic joint provides a new understanding of the inflamed joint and could explain the increased bone resorption observed in RA. Okada et al (OP 2918) performed a trans-ethnic genome-wide association study (GWAS) and in silico and de novo replication studies in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by assessing ~10 million autosomal and X-chromosomal single nucleotide polymorphisms (SNPs). The results of this comprehensive genetic study have brought some new findings on fundamental pathways and genes that contribute to RA pathogenesis, and have provided empirical evidence that the genetics of RA can ensure important information for drug discovery efforts. In the plenary session Sokolove J from the Stanford University presented their work on analysis of the immunogenicity of NET-derived citrullinated proteins in RA (OP 815). They found that citrullinated Histone 2B (cH2B) is a major auto-antigen of anti-citrullinated antibodies. Citrullinated H2B could activate macrophages via TLR4 and also cH2B immune complexes were able to induce a pro-inflammatory response in macrophages and to induce NETosis in vitro. In vivo anti-cH2B did not induce murine arthritis by themselves, however in a setting of subclinical inflammation in low-dose collagen-induced arthritis anti-cH2B exacerbated arthritis. Therefore the hypothesis was formulated that the combination of the presence of ACPAs in the serum and the generation of citrullinated antigens in the joints are needed to initiate the onset of arthritis.

Leipe et al (OP 2845) investigated the trans-differentiative capacity of Th1, Th2 and Th17 cells sorted from the peripheral blood of early, active and untreated RA patients and normal controls. They observed that while Th1 and Th2 cells demonstrated an enhanced capacity to re-differentiate into Th17 cells, Th17 cells from RA patients demonstrated a diminished re-differentiation capacity into both Th1 and Th2 directions. Increased RORC expression and the presence of a permissive histone modification state at the RORC gene locus appear to be involved in the altered Th plasticity in RA, thereby forcing Th17 cell-mediated immunity of the disease. Roeleveld et al (OP 1734) demonstrated the crucial role of IL-22 in experimental arthritis. Mice deficient for IL-1Ra and IL-22 showed a 50% reduction of arthritis incidence and significantly reduced bone damage. The treatment of IL-1Ra -/-IL-22+/+ mice with IL-22 blocking antibodies after the clinical onset of arthritis showed reduced progression on inflammation and significant inhibition on bone erosion. These findings suggest that IL-22 plays an important role both in the initiation and perpetuation of experimental arthritis and might therefore be an interesting new therapeutic target in RA. Fessler et al (OP 1737) discovered a novel senescent Treg cell subset (CD4+CD28-FoxP3+) in RA patients. These cells are expanded in the peripheral blood of RA patients while are nearly absent in normal subjects and display specific functional features such as increased apoptosis rate and production of proinflammatory cytokines. Therefore, although sharing regulatory marker with conventional Tregs, this senescent Treg cell subset favors the pro-inflammatory milieu in RA.

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

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Helga Radner, MD is a rheumatology fellow at the Medical University Vienna, currently doing a postdoctoral research fellowship at the Brigham and Women’s Hospital/Harvard Medical School in Boston, US. Her special research focus is on outcome and epidemiological research in rheumatic diseases. .

RHEUMATOID ARTHRITIS I Epidemiology, clinics and non-biologics

Helga Radner

As a grand opening of this years’ conference, Singh JA presented the “New ACR Recommendations for Management of Rheumatoid Arthritis”. In addition to the old guidelines they included new domains such as an expanded list of DMARDs including tofacitinib, new safety considerations and recommendations on vaccination, a treat-to target strategy, and discuss the tapering of therapy. What is different to current EULAR guidelines is that after MTX inadequate response, combination of traditional DMARDs as well as either TNFi, non-TNFi biologics or tofacitinib are all appropriate options as a next step. Regarding tapering of therapy, in established RA patients within low disease activity ACR recommends continuing of traditional DMARDs, TNFi, non-TNFi biologics or tofacitinib; whereas in remission tapering of those therapies is recommended. Furthermore, even in remission ACR does not recommend discontinuation of all DMARD therapies. Regarding safety issues in patients with previous serious infections abatacept is recommended over TNFi, in patients with previous treated or untreated melanoma skin cancer TNFi is recommended over tofacitinib whereas in patients with previous treated solid organ malignancy same treatment options as in patients without this condition apply. Another interesting talk by Sparks J et al (OP 818) evaluated mortality in an incident RA cohort (Incident Rheumatoid Arthritis and Risk of Mortality Among Women Followed Prospectively form 1976 to 2010 in the Nurses’ Health Study).

Due to the design of the study the authors could control for detailed clinical and lifestyle data, using a large population of incident RA cases with long time follow-up. In 34 years of prospective follow-up, after controlling for covariates, women diagnosed with RA had a two-fold higher risk of death from any cause compared to women without RA. Seropositive and seronegative women with RA had an increased risk of CVD-specific and cancer-specific mortality compared to women without RA. Interestingly, seropositive women with RA had a six-fold higher risk of respiratory specific mortality compared to non-RA women. This risk was not found in seronegative RA women. Respiratory mortality appears to be an important but understudied cause of death. Markusse IM et al (OP 817) could show that in early RA patients, with a treat-to-target treatment approach followed for 10 years, the survival rates were comparable to general Dutch population (Mortality in a Large Cohort of Patients with Early Rheumatoid Arthritis That were Treated to Target for 10 Years). This suggests that tight control and treatment targeted at DAS<2.4 could prevent the increased risk of mortality associated with RA. In a poster presented by Grigoriou A et al (OP 839), the authors addressed the conflicting data about NSAIDs and increased cardiovascular risk in general population versus RA population. In a cohort of 1089 patients with RA receiving NSAIDs (including COX-II inhibitors) and 5 years of follow up, they found no significant increase of CVD events in RA patients receiving NSAIDs compared to those without NSAIDs.

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Rogier Thurlings is a rheumatologist and translational scientist at the Radboudumc in Nijmegen, the Netherlands. He has a background in translational studies on the role of B cells and mechanism of B cell directed therapies in systemic autoimmune disease. .

RHEUMATOID ARTHRITIS II Biological therapies: anti-TNF

Rogier Thurlings

A number of studies reported on tumour necrosis factor α (TNF) inhibitors in rheumatoid arthritis (RA). Van der Maas et al (OP 500) reported a randomized controlled non-inferiority trial on down-titration of the dose of adalimumab and etanercept in 180 RA patients in disease remission. The dose reduction strategy consisted of stepwise increasing the interval between injections every 3 months until flare or discontinuation. In case of flare, the TNF inhibitors was restarted or escalated. Cumulative incidence of persistent DAS28 flare was not significantly higher in the dose reduction group compared to the usual care group (10% versus 12% of patients). Furthermore, measures of functionality and quality of life were similar between the groups. In the dose reduction group, the TNF inhibitor could successfully be stopped at 18 months in 20% of patients, the interval successfully increased in 43% and in 37% of patients no dose reduction was possible. Costs were significantly lower in the dose reduction group. Several studies reported on biomarkers to predict the clinical response to anti-TNF inhibitors. Hambardzumyan et al (OP 364) reported a comparative treatment strategy analysis. It concerned the predictive capability of the change in the multi-biomarker disease activity score (MBDA) (Vectra DA®) during MTX therapy in early RA patients as a predictor of response to subsequent non-biological triple versus biological therapy.

Patients participated in the Swedish Farmacotherapy (SWEFOT) clinical trial and received MTX monotherapy for 3 months, at which time 129 clinical non-responders (DAS28 > 3.2) were randomized to receive non-biological triple DMARD therapy or infliximab therapy with MTX. Of patients who had small/moderate decreases in MBDA score during MTX monotherapy, 43% responded to subsequent triple therapy and 57% responded to anti-TNF. In contrast, among patients with a large decreases in MBDA score from BL to month 3, 67% responded to subsequent triple therapy and 37% to anti-TNF treatment. Finally, a large amount of data concerning the cost-effectivity of anti-TNF blockade and biosimilar drugs have been presented. Bansback et al (OP 1144) presented a randomized noninferiority trial on the cost-effectiveness of adding etanercept vs. sulfasalazine and hydroxychloroquine to methotrexate therapy. 353 patients were randomized to etanercept plus methotrexate or a triple regimen. Etanercept provided marginally more quality of life over the course of 48 weeks, while an economic evaluation based on a prospective tracking of resource use showed etanercept accumulated substantially higher drug costs. The resultant cost-effectiveness ratios for etanercept vs triple regimen were $0.95 million/ quality adjusted life year over 48 weeks.

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Katerina Chatzidionysiou MD, PhD is a clinical and research fellow at Karolinska University Hospital and Karolinska Institute in Stockholm with a special focus on biological therapy in rheumatoid arthritis.

RHEUMATOID ARTHRITIS III other biologics and new drugs beyond biologics

Katerina Chatzidionysiou

Burmester et al (OP 1845) presented the 2-year clinical and radiographic results of a randomized, placebo-controlled trial, where methotrexate-naïve RA patients were randomized to treatment with tocilizumab (two different doses, 4mg/kg and 8mg/kg) + methotrexate, tocilizumab monotherapy (8mg/kg) or methotrexate monotherapy. Patients who received tocilizumab 8mg/kg + methotrexate or tocilizumab 8mg/kg monotherapy for the duration of the study had sustained improvement in disease activity and maintained joint damage inhibition over 104 weeks. Efficacy improved further in patients receiving methotrexate or tocilizumab 4mg/kg + methotrexate who switched to escape with tocilizumab 8mg/kg + methotrexate at week 52 (patients who had not achieved low disease activity); the overall degree of joint damage (though generally minor) was greater than that in patients who received tocilizumab 8mg/kg for the entire study, highlighting the importance of early initiation of optimal therapy. Safety was consistent with the known safety profile of tocilizumab.

The efficacy and safety of baricitinib in RA, an oral inhibitor of JAK1/JAK2, was investigated by Keystone et al in an open-label, long-term extension study (OP 2822). Among pts completing 128 wks (part A-D) of this phase 2b study, clinical improvements observed at week 24 were maintained or improved through week 128. No new safety signals were identified. No opportunistic infections, tuberculosis cases, or lymphomas were observed. One death due to myocardial infarction occurred in the 8 mg group. McInnes (1486) presented data from a phase 2b RCT examining the speed of clinical response to mavrilimumab, a macrophage inhibitor, and effect on the multi-biomarker disease activity score after week 1. At week 1, all mavrilimumab doses showed significant reductions from baseline in DAS28-CRP (p<0.001 vs placebo), with treatment benefit increasing to week 12. Rapid onset of clinical benefit was paralleled with reduction in MBDA score; 100 and 150 mg showed early (week 1) and sustained (week 24) significant changes in MBDA score vs placebo (p<0.01; Figure B), with greater decreases in DAS28-CRP responders vs non-responders (week 12). Approximately ≥50% decreases in serum IL-6, CRP, and serum amyloid-A protein levels were observed at week 1 and maintained during treatment. By targeting activated macrophages, mavrilimumab substantially reduced patients’ RA disease activity from first to final assessment.

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Christian Dejaco, MD, PhD is consultant and Assistant

Professor at the Medical University Graz. His main research interests are the value of ultrasound in psoriatic arthritis, clinical research on polymyalgia rheumatica and translational

research on T lymphocyte senescence in rheumatology. .

PSORIATIC ARTHRITIS Christian Dejaco

Mease et al (OP 953) reported the results of a phase III trial of Secukinumab in 397 patients with Psoriatic Arthritis (PsA). Patient were treated for 24 weeks either with 300mg, 150mg or 75 mg Secukinumab or placebo. The primary endpoint, an ACR 20 response was more frequently achieved in patients treated with Secukinumab than in the placebo group: 54.0% (300mg), 51.0% (150mg) and 29.3% (75mg) vs. 15.3%. Secukinumab was also more effective than placebo regarding secondary endpoints including ACR 50/70, PASI, SF-36 PCS, HAQ-DI, dactylitis and enthesitis. Garg et al (OP 547) retrospectively compared the clinical and imaging characteristics between 33 patients with psoriatic arthritis (axPsA) and 168 cases with axial spondyloarthritis (axSpA). They observed a higher prevalence of uveitis and HLA B27+ in axSpA patients than in axPsA, whereas no difference was found regarding radiological results such as grading of sacroileitis, symmetry or bilateralism of radiographic findings. O'Rielly et al (OP 623) compared the methylation pattern between paternally and maternally transmitted PsA to investigate the molecular basis for the known excess paternal transmission rates of psoriasis and PsA. Genome-wide DNA methylation profiling was performed in 24 patients with paternally and 24 cases with maternally transmitted disease. They observed hypermetylated regions particularly at chromosome 8. Among individual genes potentially relevant to PsA pathogenesis, a hypermethylation of CPG sites on MICA, IRIF1, PSORS1C3 and TNFS4 was found whereas an excess hypomethylation was observed on PSORS1C1.

Mease et al (1853) aimed to investigate the factors associated with the persistence of anti-TNF-α treatment in PsA using data from the US Corrona registry on 519 biologic naïve PsA receiving a TNF-α blocking agent. Almost one third of patients used the TNF-inhibitor as monotherapy. Overall, there was no difference between combination and monotherapy groups regarding the persistence of the TNF-blocker. Factors associated with a change of therapy were disability (mHAQ) and disease activity (CDAI). Etanercept monotherapy had a higher persistence than combination therapy whereas for infliximab, combination therapy persisted longer. Senabre-Gallego et al (OP 2423) investigated 26 patients with RA or PsA treated with a TNF-inhibitor at an extended administration interval. All patients underwent clinical and ultrasound examination. Colour Doppler sonography revealed a positive result in 50% of patients, however the overall score was low (mean 1.42 out of 36 points). No difference was found when comparing clinical and ultrasound scores prior (available in 17 patients) and after the administration interval extension. Mease et al (OP 952) reported the results of a 24 week, IIB randomized controlled trial on 3 different doses of Clazakizumab (25mg, 100mg, or 200mg), or placebo, tested in 165 patients with PsA. ACR20 response rates at week 16 were higher in the 100mg arm vs. placebo (52% vs 29%, p=0.039), whereas in the other dose groups, statistical significance was not reached. Concerning secondary endpoints, numerically better results were found in patients treated with Clazakizumab, however, a clear dose response was not observed.

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Mislav Radić, MD, PhD is Assistant Professor of

Internal Medicine and he is currently working in the Division of Rheumatology and Clinical Immunology University Hospital Split, Croatia. His scientific and clinical interests are

systemic sclerosis, osteoarthritis, vasculitis, epidemiology and imaging tools in rheumatology.

AXIAL SPONDYLOARTHRITIS Mislav Radić

Rheumatology rapidly progresses and new insights are getting bigger and bigger especially in the field of axial spondyloarthritis. This report is primarily focused on the latest findings in this field. I would like to start with a new possible predictor of radiographic progression in patients with ankylosing spondylitis (AS). Vertebral corner fat lesions have been shown to be associated with later development of new syndesmophytes in the same vertebral corners. Maksymowych et al (OP 591) have created a study which aims to investigate the association between fat lesions and radiographic progression at the patient level using the novel Fat Spondyloarthritis Spine Score (FASSS). The conclusion of this study was that the positive spine MRI for fat assessed with FASSS, and the degree of spinal fat are significantly associated with radiographic progression in patients with AS. This could lead us to an important target for therapeutic intervention. Furthermore, Baeten et al (OP 819) have showed us results from the randomised placebo-controlled clinical trial regarding the selective IL-17A inhibitor secukinumab that provides rapid and significant improvement of signs and symptoms in patients with active AS, regardless of prior anti-TNF exposure. Fernández-Carballido et al (OP 2578) have described health related quality of life (HRQoL), physical function (PF) and spinal mobility (SM) in patients form the Esperanza cohort with early axial spondyloarthritis (axSpA). Nevertheless, they have analyzed the associations between HRQoL, PF and SM with disease activity and radiographic damage.

They have concluded that in patients with early axSpA, HRQoL and physical function are already impaired and primarily associated with disease activity. Immunogenicity is a new issue in the AS treatment with biologics. The SpA patients treated under TNF inhibitors with detectable antidrug antibodies (ADA) often develop loss of efficacy. Concomitant therapy with methotrexate (MTX) appears to reduce the immunogenicity of biological drugs. Villalba et al (OP 1603) have presented in the cohort of SpA patients treated with infliximab and adalimumab that the use of MTX has a preventive effect on the ADA development. I would like to stress that the baseline MTX dose (<15 mg/week) is not a determinant factor to get this effect. Baraliakos et al (OP 2581) have designed double blind randomized controlled trial in purpose to determine whether untreated AS patients with clinically active disease but initially negative MRI or normal CRP, can develop objective evidence of inflammation and respond to adalimumab treatment. The main conclusion from this study was that AS patients with clinically active disease but without objective inflammation at one point, may benefit from subsequent re-testing for inflammation, and if present, from initiation of adalimumab therapy.

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Christophe Richez, MD, PhD is a Professor of

Rheumatology at Bordeaux Hospital affiliated with University of Bordeaux. His main clinical interests are lupus and rheumatoid arthritis. His research focuses on the involvement of innate

immunity in various inflammatory diseases.

SLE & APS Christophe Richez

Khamashta et al (L4) randomized 431 subjects with seropositive moderate to severe SLE, despite standard of care treatment, to receive the anti-interferon (IFN)-α antibody sifalimumab (200, 600 or 1200 mg IV every 4 weeks) or placebo for 52 weeks. The percentage achieving SLE Responder Index-4 (SRI-4) response at week 52 were significantly higher with sifalimumab 1200 mg than with placebo (59.8% vs 45.4%; p=0.031). Significant improvements of arthritis in the sifalimumab (600 and 1200 mg) vs placebo arms were also reported. There were no major unexpected safety signals. An increased frequency of occurrence of herpes zoster in patients receiving sifalimumab was identified but the response to anti-viral treatment was prompt. Preliminary results of the anti-IFN-α receptor subunit 1 antibody anifrolumab (OP 719) were also presented. This molecule, developed by the same company, blocks signaling induced by all type I IFNs, not only IFN-α . Morehouse et al showed that anifrolumab (n=17) suppresses the IFN gene signature (IFNGS) to a greater extent and for a more sustained period than sifalimumab (n=30). Again, no major safety issues were described with anifrolumab or sifalimumab in this small study. Another way to block IFN-α production was reported with the use of a novel anti-CD123 antibody CSL362, which works by inducing depletion of plasmacytoid dendritic cells (pDC) (OP 2842). Using PBMCs from lupus patients, Oon et al showed that CSL362 depletes pDCs in vitro, and therefore inhibits TLR9-induced IFN-α production and TLR9-induced upregulation of the IFNGS. .

Experience has shown that in lupus nephritis (LN), long-term follow-up and results are essential. This justifies a new analysis of the MAINTAIN nephritis trial comparing efficacy and tolerance of aziathioprine (AZA) and mycophenolate mofetil (MMF) during the maintenance phase. 10-year data of this study on the remaining 87 patients (from 105 at inclusion) were presented by Tamirou et al (OP 958)during this ACR. Renal flares were common (approximately 50%) but equally distributed between groups. Additional cyclophosphamide, immuno-suppressive and rituximab therapy was prescribed in respectively 19%, 41% and 11% of the patients. Early proteinuria reduction (24 hour protein excretion ≤ 0.5g) predicts long-term renal outcome. However, the most interesting result from this study is probably the confirmation that AZA and MMF, with 50% of renal flares, are equally ineffective maintenance therapies for LN. Results from the PLUS study are relevant to our current clinical practice. Jallouli et al (OP 1925) showed that blood hydroxychloroquine (HCQ) levels are higher in patients with renal insufficiency and low BMI, requiring therefore more frequent ophthalmological monitoring of these patients.

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Barbara Ruaro, MD, currently works at the Rheumatology

Division in Genoa, Italy. Her areas of interest are systemic sclerosis and musculoskeletal ultrasonography.

OTHER CONNECTIVE TISSUE DISEASES Barbara Ruaro

Smith et al (OP 1928) showed the results of a multicenter prospective cohort study that used nailfold videocapillaroscopy and other clinical characteristics (number of digital ulcers at baseline visit categorized into 0, 1, 2 and 3, mean number of capillaries in the middle finger of the dominant hand and presence/absence of critical digital ischemia at enrolment) to determine the risk of developing new digital ulcers in patients with scleroderma. Saketkoo et al (OP 1931) reported that mycophenolate mofetil improved survival in systemic sclerosis patients with pulmonary hypertension with a forced vital capacity of 70, even without improvement in forced vital capacity. Soldano S and colleagues (OP 1713) reported their preliminary results on the increase of CD206 cells in both the peripheral blood and skin of SSc patients. They also said that the ability of SSc serum to induce the expression of this M2 macrophage marker in PBMCs-derived macrophages might support a possible involvement of this cell subset in the pathogenesis of SSc. In Bruni et al’s (PO 1703) paper the association of malignancy with PM/Scl reactivity in SSc was demonstrated. This is of interest in the context of recent studies describing a potential pathogenic role of anti-RNA polymerase III antibodies with malignant disease in SSc.

In their work, Jin Lee et al (OP 2215) demonstrated that the clinical features of cancers associated with active myositis were distinctive from those of cancers unrelated to myositis activity in patients with myositis. The former were found to develop within 1 year of myositis in contrast to the latter and to be more advanced at diagnosis. The outcome of associated myositis in the former cases was worse in terms of muscle power recovery. Successful cancer treatment was associated with a better outcome of myositis. Patients who had cancers associated with active myositis showed poor survival compared to those who had cancers that were unrelated to myositis activity. At the end of their systematic literature review Soussan M et al (OP 2145) reported that FDG-PET has an overall valuable performance for the diagnosis of large-vessel vasculitis, especially for giant cell arteritis and for the assessment of the activity in Takayasu arteritis. In their long-term analysis, Pue´chal X et al (OP 1864) confirmed that azathioprine and methotrexate are comparable options for maintaining granulomatosis with polyangiitis or microscopic polyangiitis remission. It showed that the overall survival is good, even though relapses and adverse events remain matters of concern. Further studies are needed to reduce the long-term relapse rate of ANCA-associated vasculitides.

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João Madruga Dias, MD is a Rheumatology Consultant at

Centro Hospitalar Médio Tejo (Portugal) with a special interest in inflammatory rheumatic diseases in pregnancy, musculoskeletal ultrasound and arthroscopy. He trained arthroscopy in

Saint Vincent's University Hospital, University College of Dublin.

IMAGING João Dias

The objective of the pilot study by Ogdie et al (OP 2140) was to examine the agreement among two imaging methods (US and 18F-Flurorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT)) and physical examination in assessing joint inflammation. Agreement among the imaging modalities and examination was low (κ 0.01-0.22). Restricting the analysis to large peripheral joints did not substantially change agreement. It may be that each modality measures a distinct property of inflammation. Ng et al (OP 904) aimed to investigate, at a single joint level, the correlation of US synovitis with histological synovial inflammation before and after treatment initiation in early RA. At baseline, US power doppler (PD) was significantly correlated with histological markers of inflammation – CD3, CD68, CD68sl and CD138, and with inflammatory markers ESR and CRP. After 6 months of therapy, most of these correlations were still present, most notably with CD68sl. A fall in US PD in response to treatment at 6 months is associated with a fall in CD68sl and a fall in DAS28. This study supports that Power Doppler US is a biomarker for treatment response and reflects both clinical and histological markers of disease activity in patients with RA. Weiss et al (OP 1895) proposed to evaluate the (so-far unknown) prevalence of sacroiliitis at diagnosis in juvenile spondyloarthritis children that met criteria for enthesitis-related arthritis or psoriatic arthritis, using radiographs and MRI. Nine children had acute sacroiliitis at MRI (5 bilateral). Among these, 7 had erosions or sclerosis on MRI and 5 had changes on conventional radiography.

Of the subjects with acute sacroiliitis only 4 reported a history of back pain or tenderness on palpation of the sacroiliac joints. Meara et al (OP 2641) sought to assess indications and findings for Cardiac Magnetic Resonance (CMR) in SLE. Half of the patients who underwent CMR stress testing had abnormal perfusion. The most common abnormalities on non-stress CMR testing included abnormal myocardial T2 signal (29.8%), late gadolinium enhancement (21.3%), pericardial thickening (14.6%), and valvular abnormalities (21.7% aortic, 23.9% mitral, 17.4% tricuspid). CMR imaging identified several abnormalities not evident on other cardiovascular imaging modalities including increased T2 signal in myocardium (suggesting myocardial inflammation) and late gadolinium enhancement (suggesting fibrosis from prior ischemia/inflammation). Narayan et al (OP 2538) sought to determine the safety and utility of Ultrasound-guided core needle biopsy (CNB) in the evaluation of salivary gland abnormalities in patients with suspected or established Sjögren’s syndrome. Their results showed the utility of CNB as a diagnostic tool for salivary gland disease: 1) pathologic abnormalities (lymphoid infiltrates or >50% fibrosis) in 10/10 patients with abnormal salivary gland ultrasound echotexture and 2) lymphoid infiltrates in 5/8 patients with established SS. None of the patients reported complications one day post-procedure or during the 172-day longitudinal follow-up. A noteworthy mention to the 10 EULAR recommendations for the use of imaging in spondyloarthritis in clinical practice by Mandl et al (OP 2589).

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Paul Studenic, MD is a medical resident and clinical

research fellow at the division of rheumatology of the Medical University Vienna in Austria, working on his PhD. His main interests are rheumatoid arthritis, predictors of disease activity, outcomes

assessment with a focus on patient reported outcomes and biomarkers. He is currently engaged in the EMEUNET Website Subgroup and facebook team.

METABOLIC AND CRYSTAL ARTHROPATHIES Paul Studenic

This year’s ACR brought some new insights into gout and its associations. Lu et al (OP 827) have found that patients with gout are less likely to develop Alzheimer’s disease than healthy controls. 55471 gout patients were matched to non-gout individuals and risk factors were collected from medical records. The adjusted hazard ratio of gout vs. non gout individuals developing Alzheimer’s disease was 0.69 (0.58-0.81). Teng et al (OP 1837) reported about the association between food intake and gout. As a part of, this dietary information of 63257 Chinese adults was collected and 51114 participants without gout at baseline and follow-up data were used for analyses. They could show that poultry, fish and shell fish was associated with an increased risk of gout. Bardin et al (OP 163) showed data that the risk of skin reaction to Febuxostat is not significantly increased by a history of cutaneous adverse events because of allopurinol intake. This was based on retrospective analyses of 554 gout patients, of whom 113 have sequentially been treated with Febuxostat. Bardin T et al (OP 164) also reports of a posthoc analyses of the CACTUS trial, which included 2762 gout patients. 1513 patients did take Febuxostat after Allopurinol. 92 patients reported about adverse events due to Allopurinol and 1 had an event due to Febuxostat.

Yoon et al (OP 166) reported about risk factors for gout attack recurrence during Allopurinol treatment. By means of multiple logistic regression analyses this was investigated in 527 gout patients with a mean observation period of 3.17 years (SD: 2.64). The presence of tophi and uric acid levels >8.5mg/dl were associated with recurrence of gout. Singh et al (OP 169) investigated the risk of gout on coronary heart disease. Patient data of health plans was analyzed for the outcome stroke and myocardial infarction. In comparison to diabetes gout alone had a hazard ratio of 0.82, but gout contributed to the MI risk in diabetes patients (HR: 1.26; 1.19-1.34). The risk of a stroke was higher in patients with diabetes and gout than in patients with diabetes alone. Gout alone does not seem to be a cardiovascular risk factor.

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Ida K. Haugen, MD, PhD is a Rheumatology fellow and

post-doctoral researcher in the Department of Rheumatology at Diakonhjemmet Hospital, Oslo, Norway. Her main research interests are hand osteoarthritis, epidemiology and imaging.

OSTEOARTHRITIS & OSTEOPOROSIS Ida Haugen

Using data from the Johston County Osteoarthritis Project, Cleveland et al (OP 2941) found that poor physical function was associated with death in a cohort of individuals with knee and hip osteoarthritis. These findings were independent of co-morbidities and other risk factors for death, such as high BMI, smoking, diabetes, stroke, cardiovascular disease and depression. The associations with death were particularly strong for individuals with hip osteoarthritis, therefore suggesting a potential survival benefit through intervention among those individuals. The MOST study is a longitudinal cohort of persons with or at risk of knee OA. Using data from the 64-mo and 84-mo visits, Neogi et al (OP 2783) showed that MRI-defined Hoffa´s synovitis at baseline was associated with a decrease of pressure pain threshold (i.e. more sensitized), while MRI-defined effusion was associatwd with incident temporal summation as a marker of central sensitization. In contrast, bone marrow lesions did not appear to contribute to pain sensitization in knee osteoarthritis. In 56 consecutive hand OA patients recruited from the rheumatology outpatient, Kortekaas et al (OP 1823) showed that inflammatory ultrasound features, i.e. synovial thickening and power Doppler activity, were associated with erosive radiographic progression over 2.3 years in patients with hand osteoarthritis. These results suggest that inflammation plays a role in the pathogenesis of erosive hand osteoarthritis and could be a therapeutic target.

In an ancillary study from the 3-year randomized placebo-controlled phase III trials of strontium ranelate in knee osteoarthritis (SEKOIA trial), Courties et al (OP 1275) found that obesity was associated with structural damage of hand osteoarthritis assessed by conventional radiographs. Ischemic cardiopathy was associated with symptoms of hand osteoarthritis. Whether there exist a metabolic osteoarthritis phenotype should be further explored in future studies. In a longitudinal study of 70 patients from the Oslo hand OA cohort, Haugen et al (OP 1822) showed that increasing MRI-defined synovitis and bone marrow lesions were significantly associated with incident tenderness in the interphalangeal joints. Loss of synovitis was associated with loss of tenderness, but the association was statistically non-significant. Larger longitudinal studies and clinical trials are needed to further explore the causal associations between MRI-defined synovitis and bone marrow lesions and pain in hand osteoarthritis. Using data from the Osteoarthritis Initiative, which is a longitudinal study of persons with or at risk of knee osteoarthritis, Lo et al (OP 2895) found that self-reported non-elite running earlier in life was not associated with prevalent radiographic knee osteoarthritis or knee pain in 2439 participants. Whether running is protective of knee osteoarthritis should be further explored in longitudinal prospective studies.

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Walter Alberto Sifuentes Giraldo, MD is a research

associate at the Department of Rheumatology of the University Hospital Ramon y Cajal, Madrid, Spain. His main research interest focuses on pediatric rheumatology, spondyloarthritis and

biological therapies.

PEDIATRIC RHEUMATOLOGY Alberto Sifuentes

Brunner et al (OP 933) presented 48-week data from a phase III clinical trial of glolimumab in juvenile idiopathic arthritis (JIA). The study included 173 patients with a polyarticular course and active disease despite methotrexate therapy, who received golimumab 30 mg/m2 sc in an open label trial up to week 16 and then were randomized to continue golimumab or switch to placebo. There was a rapid response to golimumab during first 16 weeks. However, the study did not meet primary endpoint, as both groups did not differ in flare rates in the part 2. The potential use of MRP8/14 serum levels as predictor of response to anti-TNF treatment in non-systemic JIA was assessed by Anink et al (OP 932). High baseline levels of MRP8/14 predict a good response to anti-TNF treatment. Decrease of MRP8/14 after initiation of anti-TNF was associated with response to treatment, but patients with high MRP8/14 levels at time of discontinuation had a higher chance to flare. Baildam et al (OP 295) assessed the response to intraarticular corticosteroid injections (IACI) in a large prospective cohort of JIA patients in UK. They found that 24.4% required monotherapy with IACI alone and the effect of the first injection was prolonged, with a median time to second injection of 318 days.

Ravelli et al (OP 299) presented the data from a controlled trial of IACI with or without methotrexate in 207 children with active oligoarticular JIA. The flares of synovitis occurred less frequently in injected joints of patients who received concomitant methotrexate, but the association of this drug did not increase the overall effectiveness of IACI therapy, because of the high frequency of new onset of synovitis in uninjected joints. Consolaro et al (OP 277) studied the performance of ILAR classification for JIA in 12141 patients from EPOCA and Pharmachild registers, and demonstrated that in current clinical practice nearly 20% of JIA patients are categorized according to physician diagnosis attribution despite the lack of fulfilment of the ILAR exclusion criteria. Eng et al (OP 290) studied the patterns of active joint involvement in 807 treatment-naive JIA patients and identified 4 composite variables or principal components (PCs) that distinguish patients from each other: (1) overall joint count, (2) finger vs. toe involvement, (3) large vs. small joint involvement, and (4) sacroiliac joint involvement. Based on these 4 PCs, they recognized 12 distinct signatures which were able to distinguish homogeneous patient subpopulations both within and between ILAR subtypes.

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MENTOR-MENTEE PROGRAMME ACR 2014, BOSTON

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The meeting with Dr Schett, organized by EMEUNET, was a nice

opportunity to talk in a relaxed atmosphere about important

aspects of carrier building with a well-known professional.

Comments from the participants

· ”I've really enjoyed the mentor-mentee meeting. Because of the informal setting and the small groups you could ask many questions. I would have never asked these questions during an ACR session. I think this is a great opportunity for mentees to discuss with a professor with a lot of know-how about your ideas of a specific subject or career opportunities in general.”

· ”Personal talk - rather anonymous - you can ask things you cannot ask your own boss.”

· ”The meeting with Dr Schett, organized by EMEUNET, was a nice opportunity to talk in a relaxed atmosphere about important aspects of carrier building with a well-known professional.”

· ”Interactive, informative, personal, knowledgeable and lots of questions and answers. The selected Mentor who is a leader in ultrasound imaging was also able to pave a way for EMEUNET participation in EULAR activities relating to ultrasound. Excellent meeting.”

· ”The meeting was very useful as I had the opportunity to share all my worries about my future and receive good advices from an experienced researcher and from other young researcher. Although I am a shy person, as we were only four, it was easy for me to join the conversation. I would encourage other members of EUMEUNET to join this unique initiative.”

· ”Thanks for this great initiative! It was a great opportunity to discuss career steps and choices, opportunities and questions, with an independent expert in the field.”

MENTOR-MENTEE PROGRAMME DURING ACR 2014

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ITALIAN CONGRESS OF RHEUMATOLOGY The Italian Society for Rheumatology (SIR) national meeting was held from

Wednesday 26 to Saturday 29 November in Rimini, Italy. The meeting welcomed doctors and scientific specialists working in the field of Rheumatology including consultants, trainees, scientists and researchers from Italy. In addition, symposia in

collaboration with the Hungarian Association of Rheumatologists, the German Rheumatology Association, the

French Society of Rheumatology and the Chinese Rheumatology Association

were also held. This year, we had for the first time a Session for Young Rheumatologists to discuss how to build a national network, and to promote education/career possibilities in Italy and abroad. EMEUNET was highlighted within this

session as a brief powerpoint presentation was given to explain aims and organization of EMEUNET and to

encourage young Italian clinicians and scientists to join our expanding network.

During the Young Rheumatologists Session EMEUNET flyers were also circulated to provide attendees with all information at a glance. Sara Monti EMEUNET Country Liaison

for Italy, Alessia Alunno and Serena

Bugatti EMEUNET Working Group members

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EMEUNET AT THE NATIONAL CONGRESSES

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On 28th November 2014 I presented EMEUNET for the first time at the Slovenian Rheumatology Meeting in Portorož, Slovenia.

EMEUNET'S FIRST TIME AT THE SLOVENIAN CONGRESS OF RHEUMATOLOGY On 28th November 2014 I presented EMEUNET for the first time at the Slovenian Rheumatology Meeting in Portorož, Slovenia. Slovenian young rheumatologists, researchers and the heads of Slovenian cl inical and research rheumatology have already known EMEUNET and me - as EMEUNET’s Country Liaison for Slovenia - from the regular EMEUNET's e-mails, the EMEUNET Corner, EMEUNET's newsletters, participation in surveys, etc. However, it was absolutely great to finally put the names from my e-mail list to the faces, to meet Slovenian young rheumatologists in real and to present the EMEUNET nationally. Here, I would like to sincerely thank Prof. Dr. Iztok Holc, Prof. Dr. Matija Tomšič and Prof. Dr. Snežna Sodin Šemrl, who absolutely supported the idea of EMEUNET from the very beginning and made it possible for me to present

the EMEUNET at the Slovenian Rheumatology Meeting. I presented EMEUNET with a 15 minute talk followed by a vivid discussion with Slovenian rheumatologists about the advantages of EMEUNET, how to promote EMEUNET nationally and how to increase the active participation of young Slovenian rheumatologists and researchers in the EMEUNET. I could also personally discuss with young Slovenian rheumatologists their views of the EMEUNET and EMEUNET's membership, their specific needs and how EMEUNET could help to address them, as well as their plans for the future to actively participate in EMEUNET's endeavours as EMEUNET's working group members or the next country liaisons. The feedback on EMEUNET was great with strong support from everyone in Slovenian rheumatology.

The first plans were set with the heads of Slovenian rheumatology and young people for future EMEUNET activities on national level and within the EMEUNET. The national membership in the EMEUNET clearly increased in days after the meeting. This was an inspiring meeting and a great experience - real EMEUNET spirit ! and great welcome to the EMEUNET in Slovenia. Thank to everyone again!

Mojca Frank-Bertoncelj, Country Liaison of EMEUNET for

Slovenia.


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IRISH CONGRESS OF RHEUMATOLGY Annual Meeting of the Irish Society for Rheumatology 2014 Prof. Gerry Wilson (Arthritis Ireland Chair of Rheumatology) and Prof David Kane (President of Irish Society for Rheumatology) promoting EMEUNET with PhD student Sian Cregan

Eimear Linehan with newly recruited EMEUNET member Karen Creevey

Existing EMEUNET members discussing the opportunities available as part of EMEUNET

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DUTCH CONGRESS OF RHEUMATOLOGY


POLISH CONGRESS OF RHEUMATOLOGY

Polish Young Rheumatologists meeting at the Congress of Polish Society of Rheumatology in Katowice. We have been discussing current EMEUNET recruitment in Poland and chances for further promotion of EMEUNET with polish Young Rheumatologists and the chair of Polish Society of Rheumatology. Our members also won some prizes at the 5 km fun-run that accompanied the congress !.

photos by Marcin Milchert

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WHY BECOME AN EMEUNET MEMBER? AT A GLANCE

Education & skills: Widen your horizon: travel bursaries to the EUREKA translational medicine course are offered yearly by EULAR exclusively to EMEUNET members Become a reviewer: state of the art peer-review mentoring in collaboration with the Annals of Rheumatic Diseases Career development: Make a difference: become actively involved in EMEUNET/EULAR initiatives -suggest and chair a session at the EULAR Congress, and participate in shaping the upcoming EULAR guidelines! News and updates: Get the best out of EULAR and ACR Congresses: our newsletters guide you so that you “do not miss” key presentations and post-congress “highlights” Stay up to date: receive regular mementos of upcoming international events in Rheumatology and related fields Research opportunities: Find a mentor: don’t miss the mentor-mentee meetings, yearly at the EULAR Congress. Be the first to apply: fellowships and open positions in research are regularly advertised to our members Networking: Find collaborators: search the EMEUNET membership database and the upcoming EULAR Centers of Excellence database Make friends: take part in EMEUNET sightseeing tours and events







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THE SELECTION OF PRESENTATIONS FOR THIS NEWSLETTER IS TOTALLY PERSONAL, LIMITED

AND CONSECUTIVELY VERY INCOMPLETE.

More information about EMEUNET can be found in http://emeunet.eular.org. and www.facebook.com/EMEUNET

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

EMEUNEWS DECEMBER14

the emerging eular network 2014-12 acr.pdfthe emerging eular network edition december 2014 acr 2014...

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