Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B cells

Arthritis Rheum. 2002 Aug;46(8):2029-33. doi: 10.1002/art.10467.

Abstract

Objective: The pathogenetic role of B cells in rheumatoid arthritis (RA) is under debate, but it is currently believed to be marginal. The availability of selective anti-B cell treatment provides a unique opportunity to clarify this issue. This study was undertaken to investigate the effects of B cell blockade in the treatment of refractory RA, and to evaluate the implications with regard to the role of B cells in the disease.

Methods: Five female patients with active, evolving erosive RA were treated with rituximab, an anti-CD20 chimeric monoclonal antibody. All 5 patients had been nonresponders to combination therapy with methotrexate plus cyclosporin A. Two of the 5 had also failed to respond to anti-tumor necrosis factor alpha therapy. All of these treatments were discontinued 1 month before institution of anti-CD20 therapy.

Results: Marked clinical improvement was observed in 2 patients (American College of Rheumatology 70% response [ACR70] and ACR50, respectively), starting at the end of the second month after institution of anti-CD20 therapy (month 2) and lasting until month 10 in 1 patient (articular relapse) and month 12 in the other (last followup). ACR20 response was observed in 2 additional patients, lasting until month 5 and month 7, respectively (articular relapse in both). Decrease or normalization of serum C-reactive protein and rheumatoid factor levels were observed in these patients. In contrast, patient 3 had no response to the treatment. RA synovitis and evolving erosive damage were decreased in patients exhibiting a major response, as demonstrated by imaging studies.

Conclusion: Our finding of the clinical efficacy of selective B cell blockade indicates that B cells play a critical role in rheumatoid synovitis, at least in a subset of patients. Qualitative or quantitative differences in B cell commitment in RA pathobiology might have a function in the different responses observed.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / immunology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology*
  • B-Lymphocytes / immunology*
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Immunosuppression*
  • Infusions, Intravenous
  • Middle Aged
  • Rituximab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antineoplastic Agents
  • Rituximab