Improvement of refractory rheumatoid arthritis after depletion of B cells

Scand J Rheumatol. 2004;33(2):82-6. doi: 10.1080/03009740310004379.

Abstract

Objective: B cells are involved in the pathogenesis of rheumatoid arthritis (RA). To evaluate the effect of therapeutic B-cell depletion for treatment of RA, an open label study has been performed using the B-cell depleting anti-CD20 antibody rituximab.

Methods: Five patients with refractory RA were treated weekly with four infusions of rituximab (375 mg/m2) alone, or in combination with ongoing methotrexate (MTX). Patients were followed for at least 44 weeks and monitored for safety and tolerability of treatment.

Results: Treatment could be performed without serious side effects and resulted in peripheral B-cell depletion lasting between 36 weeks up to > 1 year. The follow-up revealed no significant treatment-associated side effects. At 22 weeks, 4/5 patients showed a significant improvement (> 1.2) of the Disease Activity Score (DAS28). The mean DAS28 of all patients declined from 6.2 to 4.1. At 44 weeks there was one drop-out, another patient still had a sustained response, and three patients showed slowly increasing disease activity (mean DAS28 of the remaining four patients: Week 0: 6.0; Week 22: 3.85; Week 44: 5.6). Despite relatively constant immunoglobulin levels, rheumatoid factor levels decreased parallel to disease activity.

Conclusion: In patients with refractory RA, B-cell depletion with rituximab is safe and well tolerated. A reduction of disease activity could be observed, which eventually deteriorated after B-cell repopulation. The findings give more evidence for B-cell targeted therapies in RA.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Murine-Derived
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Pain Measurement
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Rituximab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab
  • Methotrexate