Dr. Salama has received consulting fees, speaking fees, and/or honoraria from Roche and Novartis (less than $10,000 each).
A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis
Article first published online: 29 JUN 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 7, pages 2156–2168, July 2009
How to Cite
Jones, R. B., Ferraro, A. J., Chaudhry, A. N., Brogan, P., Salama, A. D., Smith, K. G. C., Savage, C. O. S. and Jayne, D. R. W. (2009), A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis. Arthritis & Rheumatism, 60: 2156–2168. doi: 10.1002/art.24637
- Issue published online: 29 JUN 2009
- Article first published online: 29 JUN 2009
- Manuscript Accepted: 1 APR 2009
- Manuscript Received: 15 JUL 2008
- National Institute for Health Research Cambridge Biomedical Research Centre
- MRC Clinical Research Training Fellowship
- National Institute for Health Research Imperial College Biomedical Research Centre
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.
Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used.
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 Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%).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/m2 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 ≥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.
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.