Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion

Ann Rheum Dis. 2002 Oct;61(10):883-8. doi: 10.1136/ard.61.10.883.

Abstract

Objectives: To obtain evidence for dose response and to extend evidence of safety and efficacy for B lymphocyte depletion in rheumatoid arthritis.

Methods: Twenty two patients with rheumatoid arthritis received a total of 29 treatments with five different combinations of rituximab (RTX), cyclophosphamide (CP), and/or high dose prednisolone (PR) on an open basis as follows; cohort I: RTX 1400 mg/m(2), CP 750x2+PR; cohort II: RTX 300-700 mg/m(2), -CP+/-PR); cohort III: RTX 600-700 mg/m(2), CP 750x2+PR; cohort IV: RTX 1200 mg/m(2), CP 750x2-PR; cohort V: RTX 500 mg/m(2), CP 750x2+PR. American College of Rheumatology (ACR) criteria of improvement at six months were chosen as the primary outcome measure. Disease activity scores and total duration of improvement and of B cytopenia were also recorded.

Results: No major adverse events attributable to treatment were seen. ACR grades of improvement at six months were as follows: cohort I: ACR70x3, ACR50x2; cohort II: ACR20x1, ACR0x3; cohort III: ACR70x6, ACR50x2, ACR20x2; cohort IV: ACR70x2, ACR50x2, ACR20x1, ACR0x1; cohort V: ACR0x4.

Conclusions: B lymphocyte depletion in rheumatoid arthritis has so far proved to be safe and associated with major improvement with protocols including RTX 600 mg/m(2) or more and CP, but not with more limited protocols. These observations provide an initial basis for the design of formal trials of B cell depletion and other B cell directed treatments, including a phase II controlled trial now in progress.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / therapy*
  • B-Lymphocytes / drug effects*
  • Combined Modality Therapy
  • Cyclophosphamide / therapeutic use
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphocyte Depletion / methods*
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use
  • Rituximab
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Rituximab
  • Cyclophosphamide
  • Prednisolone