Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial

PLoS One. 2015 Nov 5;10(11):e0133702. doi: 10.1371/journal.pone.0133702. eCollection 2015.

Abstract

Objective: Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.

Methods: Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.

Results: Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718) to 74.5 IU/L (range, 40-47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10-70) to 9 mg/d (range, 7-65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.

Conclusions: This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.

Trial registration: Clinicaltrials.gov NCT00774462.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / immunology*
  • Creatine Kinase / blood
  • Female
  • Humans
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Myositis / drug therapy*
  • Rituximab / therapeutic use*
  • Treatment Outcome
  • Vital Capacity
  • Young Adult

Substances

  • Autoantibodies
  • Immunologic Factors
  • Rituximab
  • Creatine Kinase

Supplementary concepts

  • Antisynthetase syndrome

Associated data

  • ClinicalTrials.gov/NCT00774462

Grants and funding

This study was supported by the French Ministry of Health (PHRC) and the Association Française contre les Myopathies (AFM). Rituximab was kindly provided by Roche. The authors state that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.