A multicenter, open-label, comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease

Semin Arthritis Rheum. 2017 Apr;46(5):625-631. doi: 10.1016/j.semarthrit.2016.10.003. Epub 2016 Oct 13.

Abstract

Objectives: Rituximab (RTX) may favorably affect lung function and skin fibrosis in patients with systemic sclerosis (SSc). We aimed to assess long-term efficacy and safety of RTX in SSc compared to standard treatment.

Methods: A total of 51 patients with SSc-associated interstitial lung disease were recruited and treated with RTX (n = 33) or conventional treatment (n = 18). Median follow-up was 4 years (range: 1-7). Conventional treatment consisted of azathioprine (n = 2), methotrexate (n = 6), and mycophenolate mofetil (n = 10).

Results: Patients in the RTX group showed an increase in FVC at 2 years (mean ± SD of FVC: 80.60 ± 21.21 vs 86.90 ± 20.56 at baseline vs 2 years, respectively, p = 0.041 compared to baseline). In sharp contrast, patients in the control group had no change in FVC during the first 2 years of follow-up. At the 7 year time point the remaining patients in the RTX group (n = 5) had higher FVC compared to baseline (mean ± SD of FVC: 91.60 ± 14.81, p = 0.158 compared to baseline) in contrast to patients in the control group (n = 9) where FVC deteriorated (p < 0.01, compared to baseline). Direct comparison between the 2 groups showed a significant benefit for the RTX group in FVC (p = 0.013). Improvement of skin thickening was found in both the RTX and the standard treatment group; however, direct comparison between groups strongly favored RTX at all-time points. Adverse events were comparable between groups.

Conclusions: Our data indicate that RTX has a beneficial effect on lung function and skin fibrosis in patients with SSc. Randomized controlled studies are highly needed.

Keywords: B cells; Fibrosis; Interstitial lung disease; Rituximab; Scleroderma; Systemic sclerosis.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kaplan-Meier Estimate
  • Lung / drug effects
  • Lung / pathology
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / drug therapy*
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Retrospective Studies
  • Rituximab / administration & dosage*
  • Rituximab / adverse effects
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / drug therapy*
  • Skin / drug effects
  • Skin / pathology
  • Time Factors

Substances

  • Immunosuppressive Agents
  • Rituximab