Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Effects and Safety of Rituximab in Systemic Sclerosis: An Analysis From the European Scleroderma Trial and Research Group.

Jordan1,  Suzana, Distler2,  Jorg HW, Maurer1,  Britta, Van Laar3,  Jacob M., Allanore4,  Yannick, Distler1,  Oliver, EUSTAR Rituximab Group,  

University Hospital Zurich, Zurich, Switzerland
Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
Musculoskeletal Research Group, Newcastle, United Kingdom
Paris Descartes University, Rheumatology A department, Cochin Hospital, Paris, France

Background/Purpose:

Preclinical studies and smaller case-series suggest potential effects of Rituximab (RTX) on skin fibrosis, interstitial lung disease and polyarthritis in patients with systemic sclerosis (SSc). Objective of this study was to analyze the effects and safety of RTX in a real-life clinical setting using the EUSTAR cohort.

Methods:

Patients treated with RTX were captured from the EUSTAR cohort and centers were asked to provide additional data for this study. Primary outcomes were: modified Rodnan skin score (mRSS) for skin fibrosis, FVC for SSc-ILD, DAS 28 3v for SSc-associated polyarthritis, and CK levels for SSc-associated myositis. Effects on fibrosis were analyzed at the follow up closest to 12 months, and effects on polyarthritis and myositis at the follow up closest to 6 months. Normally distributed data are shown as mean ± SD and were analyzed by paired t-test. Nonparametric data are shown as median and interquartile range and were analyzed by Wilcoxon matched paired signed rank test.

Results:

Seventy two SSc patients treated with RTX from 27 EUSTAR centers were available for analysis (52 diffuse SSc/19 limited SSc, disease duration 6 years (3–10 years)). The most frequent application scheme was 2 × 1000mg RTX given 2 weeks apart. Twenty-eight patients had co-treatment with other disease modifying drugs (most frequent methotrexate, n =14).

The mRSS as the primary outcome for skin fibrosis showed a statistically significant reduction compared to baseline (n=47, 18.2+10.9 vs. 14.5+9.9, p=0.0002). This effect became even more evident when the cohort was enriched for patients with extended skin fibrosis (diffuse SSc with mRSS >16 at baseline, n= 26: 26.5+6.8 vs. 20.4+8.9, p<0.0001). This was paralleled by an improvement of the European SSc activity score (n=10; 3.7 (2.6–6.4) vs. 1.7 (0.9–2.5), p=0.01).

There were no effects on FVC in patients with SSc-ILD (n=11, 57.7+9.1 vs. 56.2+16.0 %; p=0.5). Similarly, other lung function parameters including DLCO, TLC, and extent of fibrosis on HRCT did not change after RTX treatment.

In patients with SSc-associated polyarthritis, the DAS 28 score was reduced after RTX treatment (n=8; 4.8 (2.5–7.5) vs. 3.7 (2.6–6.6)), but did not reach statistical significance (p=0.3). Other arthritis outcomes including tender joint count, swollen joint count, VAS articular pain, CRP and ESR showed similar trends.

Levels of CK decreased significantly in patients with SSc-associated myositis after RTX treatment (n=12, 273+177 vs. 184+139, p=0.03). Other measures of myositis such as levels of myoglobin and VAS scores were available only for a limited number of patients and did not change significantly versus baseline.

During RTX treatment, infections occurred in 14 patients, 29 reported fatigue, 9 had nausea and 3 patients developed serum sickness. Four patients died, one of them possibly related to RTX (pneumonia and cardiac failure 1.5 months after RTX infusion).

Conclusion:

In this large, observational multicenter EUSTAR study, positive signals for potential efficacy of RTX were obtained for skin fibrosis and SSc-related myopathy. These results strongly emphasize the need for a randomized controlled trial with RTX in patients with SSc.

To cite this abstract, please use the following information:
Jordan, Suzana, Distler, Jorg HW, Maurer, Britta, Van Laar, Jacob M., Allanore, Yannick, Distler, Oliver, et al; Effects and Safety of Rituximab in Systemic Sclerosis: An Analysis From the European Scleroderma Trial and Research Group. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :702
DOI:

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