Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial

Arthritis Rheum. 2013 Feb;65(2):314-24. doi: 10.1002/art.37754.

Abstract

Objective: To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients.

Methods: Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures (CSMs) for adults. Juvenile DM patients required ≥3 abnormal CSMs, with or without muscle weakness. Patients were randomized to receive either rituximab early or rituximab late, and glucocorticoid or immunosuppressive therapy was allowed at study entry. The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement (DOI) between the 2 groups. The secondary end points were the time to achieve ≥20% improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8.

Results: Among 200 randomized patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no difference in the time to achieving the DOI between the rituximab late (n = 102) and rituximab early (n = 93) groups (P = 0.74 by log rank test), with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary end points also did not significantly differ between the 2 treatment groups. However, 161 (83%) of the randomized patients met the DOI, and individual CSMs improved in both groups throughout the 44-week trial.

Conclusion: Although there were no significant differences in the 2 treatment arms for the primary and secondary end points, 83% of adult and juvenile myositis patients with refractory disease met the DOI. The role of B cell-depleting therapies in myositis warrants further study, with consideration for a different trial design.

Trial registration: ClinicalTrials.gov NCT00106184.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Child
  • Dermatomyositis / drug therapy*
  • Double-Blind Method
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Muscle Weakness / drug therapy
  • Pain Measurement
  • Placebos
  • Polymyositis / drug therapy*
  • Rituximab
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Glucocorticoids
  • Placebos
  • Rituximab

Associated data

  • ClinicalTrials.gov/NCT00106184