S.13.1 Safety and efficacy of rituximab in SSc: an analysis from the European Scleroderma Trial and Research Group

ii25 SESSION 13 TREATMENT S.13.1 SAFETY AND EFFICACY OF RITUXIMAB IN SSc: AN ANALYSIS FROM THE EUROPEAN SCLERODERMA TRIAL AND RESEARCH GROUP S. Jordan1, J. Distler2, B. Maurer1, Y. Allanore3, J. Van Laar4 and O. Distler1 on behalf of the EUSTAR Rituximab Group1,2,3,4 1 Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland, 2Department of Internal Medicine 3, Erlangen, Germany, 3 Université Paris Descartes Hôpital Cochin, Service de Rhumatologie A and INSERM, Paris, France and 4Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK. Objectives. Objective of this multicentre, observational study was to assess effects and safety of rituximab (RTX) using the European Scleroderma Trial and Research Group (EUSTAR) cohort. Methods. EUSTAR centres were asked to provide specific data about SSc patients treated with RTX. Primary endpoints were predefined for different disease manifestations and compared between baseline and follow-up. Normally distributed data, analysed by paired t-test, are shown as mean (S.D.), and non-parametric data, analysed by Wilcoxon matched paired signed-rank test, are shown as median and interquartile range. Results. Data on 72 SSc patients treated with RTX were captured from 27 EUSTAR centres (51 females/21 males, 52 diffuse/19 limited, age 51 (44–60) years, disease duration 6 (3–10) years, 47 anti-Scl-70 positive). The most frequent RTX application scheme was 1000 mg  2 within 2 weeks (57/72 patients). Co-treatment with other immunosuppressive drugs was reported in 28 patients. The modified Rodnan skin score (mRSS) significantly decreased vs baseline at 7 (5–9) months follow-up (n ¼ 47, 18.2 þ 10.9 vs 14.5 þ 9.9, P ¼ 0.0002). This was true for both patients with later disease stages and also for patients with earlier, extended skin fibrosis (dSSc with mRSS >16 at baseline, n ¼ 26; 26.5 þ 6.8 vs 20.4 þ 8.9, P < 0.0001, reduction by 29.9%). S-HAQ was unchanged, but the European SSc activity score improved after rituximab treatment [n ¼ 10; 3.7 (2.6–6.4) vs 1.7 (0.9–2.5), P ¼ 0.01]. RTX had no effects on lung fibrosis (FVC, DLCO, TLC, HRCT score) in n ¼ 11 patients with evidence for SSc-ILD. In SSc-polyarthritis patients, the DAS-28 declined at 6 months followup without reaching statistical significance [n ¼ 8; 4.8 (2.5–7.5) vs 3.7 (2.6–6.6); p ¼ 0.3]. Of 8, 5patients were RF and/or anti-CCP antibody positive. Similar results were obtained for secondary outcome measures (tender and swollen joint count, VAS, CRP, ESR). Additional positive effects of RTX were seen on SSc-related myopathy (CK levels, 273 þ 177 vs 184 þ 139; n ¼ 12, P ¼ 0.03) and on digital ulcers [total number per patient 1 (1–3) vs 0 (0–1); n ¼ 23; P ¼ 0.0086]. During RTX treatment 14 patients had infections, 3 serum sickness, 2 allergic reactions and 1 lung fibrosis aggravation, 29 fatigue and 9 nausea. Four patients died, one possibly related to RTX treatment (pneumonia and cardiac failure 1.5 months after RTX infusion). Conclusion. This large EUSTAR cohort study points at positive effects of RTX in particular on skin fibrosis, and suggests randomized controlled trial in SSc patients. S.13.2 ORAL IMATINIB FOR THE TREATMENT OF SCLERODERMA PULMONARY INVOLVEMENT: PRELIMINARY RESULTS OF A PILOT STUDY P. Fraticelli1, G. Pomponio1, B. Gabrielli1, P. Riboldi2, G. Ferraccioli3, G. Valentini4, S. Bombardieri5, W. Malorni6, R. Gerli7, C. Lunardi8, P. Faggioli9, A. Corvetta10 and A. Gabrielli1 1 Medical and Surgical Science Department, Università Politecnica delle Marche, Internal Medicine Section, Ancona, 2Department of Internal Medicine, Istituto Auxologico Italiano, Università di Milano, Milan, 3Istituto di Reumatologia, Università Cattolica, Rome, 4Unità di Reumatologia, Seconda Università di Napoli, Naples, 5Unità di Reumatologia, Università di Pisa, Pisa, 6Dipartimento del Farmaco, Istituto Superiore di Sanità, Rome, 7Unità di Reumatologia, Università di Perugia, Perugia, 8Dipartimento di Medicina, Università di Verona, Verona, 9Unità di Medicina Interna, Ospedale Civile di Legnano, Legnano and 10Unità di Medicina Interna, Ospedale Infermi di Rimini, Rimini, Italy. Background. Pulmonary involvement (PI) represents a major cause of death of scleroderma patients. CYC showed a small beneficial effect in RCTs, but a large portion of patients appeared to be totally refractory. Since activation of tyrosine kinases may be involved in the pathogenesis of scleroderma, we have decided to test the effect of imatinib mesylate, a tyrosine kinases inhibitor, on pulmonary and skin fibrosis in a cohort of scleroderma patients, refractory to conventional therapy. Materials and methods. This study, a Phase II multicentric open trial, is focused on 30 consecutive patients with active pulmonary involvement defined as: Grade 2 dyspnoea (Mahler Dyspnea Index) plus interstitial alveolitis (CT scan showing ground-glass in two lung segments OR neutrophilic/eosinophilic alveolitis), refractory to CYC (6 g for a minimum of 3 months). The study follows a ‘Simon’s two-stage design’: 10 patients are enrolled in a first phase. A ‘good response to the treatment’ is required in at least 10% of patients before starting the second phase of enrolment (20 patients). The drug will be rejected if the final observed response rate will be in <30% of patients. Patients are treated with oral imatinib, 200 mg/day for 6 months. A ‘good response’ is defined as the improvement of PI measured trough predefined clinical, functional and radiological criteria in presence of a fair drug tolerance. Secondary outcomes are: cutaneous involvement (mRSS) and laboratory evidence of reduced skin fibroblast activation. Results. In the first phase, three patients (30%) matched the criteria for a ‘good response’: two patients (diffuse, late SSc) have shown an increase of >15% in FVC rate and one patient (limited, early SSc) an increase of >15% of DLCO and an improved CT scan pattern after 6 months of treatment. Four severe adverse effect, all judged as unrelated to the study drug, were recorded. No data about cutaneous involvement are still available and no laboratory investigation on biological samples has been performed so far. The second phase is under way and the results will be available in few months. Conclusions. If the available data will be confirmed by the final assessment, imatinib mesylate appears effective and tolerable in a subgroup of scleroderma patients with pulmonary involvement refractory to conventional treatment. These results warrant further investigations and a randomized placebo controlled trial. S.13.3 PHARMACOLOGICAL INHIBITION OF MPGES-1 RESULTS IN REDUCED PRO-FIBROTIC AND PRO-INFLAMMATORY SIGNALLING IN HUMAN SCLERODERMA FIBROBLASTS P. Ghassemi1, M. Baron2, M. Blati1 and M. Kapoor1 1 University of Montreal and 2Jewish General Hospital, Montreal, Canada. Aim. To determine the specific role of microsomal prostaglandin E synthase-1 (mPGES-1) in scleroderm (...truncated)