A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis

Arthritis Rheum. 2009 Jul;60(7):2156-68. doi: 10.1002/art.24637.


Objective: B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA-associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as re-treatment biomarkers.

Methods: Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used.

Results: All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P = 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty-eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m(2) each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty-eight patients received >or=2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty-six serious adverse events occurred, including 2 episodes of late-onset neutropenia, which were attributed to rituximab.

Conclusion: Rituximab was effective remission induction therapy for refractory ANCA-associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re-treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re-treatment.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / metabolism*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Biomarkers / metabolism
  • Child
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Remission Induction
  • Retrospective Studies
  • Rituximab
  • Secondary Prevention
  • Treatment Outcome
  • Vasculitis / drug therapy*
  • Vasculitis / immunology*
  • Young Adult


  • Antibodies, Antineutrophil Cytoplasmic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Biomarkers
  • Rituximab