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FRI0265 Rituximab improves skin fibrosis and prevents worsening of lung function in patients with systemic sclerosis in the eustar cohort
  1. S. Jordan1,
  2. J. Distler2,
  3. B. Maurer1,
  4. D. Huscher3,
  5. Y. Allanore4,
  6. J. van Laar5,
  7. O. Distler1
  8. and EUSTAR
  1. 1Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
  2. 2Department of Internal Medicine 3, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen
  3. 3German Rheumatism Research Centre, Berlin, Germany
  4. 4Service de Rhumatologie A & INSERM 1016, Université Paris Descartes, Paris, France
  5. 5Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, United Kingdom


Background There is pathophysiological rationale and clinical data from case series suggesting a potential role for B-cell targeting in the treatment of systemic sclerosis (SSc).

Objectives To assess the effect of RTX on skin and lung fibrosis in SSc patients derived from the EUSTAR cohort compared to untreated matched controls.

Methods Twenty-seven EUSTAR centers participated in this retrospective observational cohort study. Inclusion criteria were fulfillment of ACR classification criteria, Rituximab treatment, at least one follow up, modified Rodnan skin score (mRSS) >16 at baseline for the analysis on skin fibrosis and forced vital capacity (FVC) <70% predicted plus evidence of lung fibrosis on HRCT at baseline for the analysis on lung fibrosis. RTX-treated patients were matched with control patients from the EUSTAR database who were not treated with RTX. Matching parameters for skin fibrosis were: mRSS (max±25%), follow up duration (max±3months), scleroderma subtype (diffuse or limited), disease duration (best match), and concomitant immunosuppressive medication. Matching parameters for lung fibrosis were: FVC (max±10%), follow up duration (max±3 months), disease duration (best match), and immunosuppressive co-treatment. Primary endpoints were mRSS for skin fibrosis and FVC for lung fibrosis compared between RTX treated and control patients at follow up. Normally distributed data are shown as mean ± SEM 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 Twenty-five patients were recruited for the skin fibrosis analysis. Disease duration was 5 (3-7) years and follow up was 6 (5-9) months. In RTX treated patients, the mRSS was significantly reduced at follow up compared to baseline (26.6±1.4 vs. 20.3+1.8; p=0.0001). To prove that the observed decrease of the mRSS occurred due to an effect of RTX and did not simply reflect the natural course of the disease, we matched the RTX treated patients with 25 untreated controls from the EUSTAR database. This analysis confirmed the RTX effects by showing a significant reduction of the mRSS at follow up in RTX treated patients compared to matched controls (-24.0±5.2% vs. -7.5±4.3; p=0.02). Secondary endpoints such as the European disease activity score showed also significant effects of RTX.

Nine patients were recruited for the lung fibrosis analysis. Disease duration was 5.5 (2.7-11.5) years and follow up was 7.5 (5-9) months. Compared to baseline, FVC and DLCO were unchanged after RTX treatment (60.6±2.4 vs. 61.3±4.1%; p=0.7). However, FVC declined in the control group, and treatment with RTX prevented significantly the further decline of FVC (RTX group: 0.4±4.4% vs. Control group: -7.8±3.8%; p=0.02). DLCO values did not show differences between RTX treated patients and matched controls at follow up.

Conclusions The comparison of RTX treated and untreated matched control SSc patients from the EUSTAR cohort demonstrated that RTX improved skin fibrosis and prevented worsening of lung fibrosis. These results have to be confirmed in prospective randomized controlled trials.

Disclosure of Interest S. Jordan: None Declared, J. Distler: None Declared, B. Maurer: None Declared, D. Huscher: None Declared, Y. Allanore: None Declared, J. van Laar: None Declared, O. Distler Grant/Research support from: Actelion, Pfizer, Ergonex and Sanofi, Consultant for: Actelion, Pfizer, Ergonex, BMS, Sanofi-Aventis, United BioSource Corporation, medac, 4D Science, Boehringer-Ingelheim, Active Biotech and Roche, Speakers Bureau: Actelion, Pfizer, Encysive and Ergonex.

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