ARTHRITIS & RHEUMATISM Vol. 60, No. 7, July 2009, pp 2156–2168 DOI 10.1002/art.24637 © 2009, American College of Rheumatology A Multicenter Survey of Rituximab Therapy for Refractory Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Rachel B. Jones, 1 Alastair J. Ferraro, 2 Afzal N. Chaudhry, 1 Paul Brogan, 3 Alan D. Salama, 4 Kenneth G. C. Smith, 5 Caroline O. S. Savage, 2 and David R. W. Jayne 1 Objective. B cell depletion with rituximab has allowed remissions in relapsing or refractory antineu- trophil cytoplasmic antibody (ANCA)–associated vascu- litis 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 co- hort. 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 collec- tion 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 Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%).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 (me- dian 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 >2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, al- though 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 vas- culitis 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. Antineutrophil cytoplasmic antibody (ANCA)– associated vasculitis is a multisystem autoimmune dis- ease characterized by ANCA production and small- vessel inflammation. The ANCA-associated vasculitides comprise Wegener’s granulomatosis (WG), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), which have similar clinical and serologic features and similar treatment responses. Standard immunosuppressive therapies for Supported by the National Institute for Health Research Cambridge Biomedical Research Centre. Dr. Ferraro’s work was supported by an MRC Clinical Research Training Fellowship. Dr. Salama’s work was supported by the National Institute for Health Research Imperial College Biomedical Research Centre. 1 Rachel B. Jones, BSc, MBBS, MRCP, Afzal N. Chaudhry, BSc, MBBS, PhD, FRCP, David R. W. Jayne, MD, FRCP: Adden- brooke’s Hospital, Cambridge, UK; 2 Alastair J. Ferraro, BM, MCh, MRCP, Caroline O. S. Savage, FRCP, FMedSci: University Hospital, Birmingham, UK; 3 Paul Brogan, BSc, MBChB, MRCPCH, MSc, PhD: Great Ormond Street Hospital for Children, London, UK; 4 Alan D. Salama, MBBS, PhD, FRCP: Hammersmith Hospital, London, UK; 5 Kenneth G. C. Smith, PhD, FRACP, FRCPA, FRCP, FMedSci: Addenbrooke’s Hospital, and University of Cambridge School of Clinical Medicine, Cambridge, UK. Dr. Salama has received consulting fees, speaking fees, and/or honoraria from Roche and Novartis (less than $10,000 each). Dr. Smith has received an honorarium from Roche for attending an Advisory Board meeting (less than $10,000). Dr. Savage has received consulting fees from Talecris Biotherapeutics and Biovitrum and speaking fees from Roche (less than $10,000 each). Dr. Jayne has received consulting fees, speaking fees, and/or honoraria from Roche concerning rituximab (less than $10,000), as well as research grant support from Roche for investigator-initiated studies. Address correspondence and reprint requests to Rachel B. Jones, BSc, MBBS, MRCP, Vasculitis Office, Box 118, Renal Unit, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, UK. E-mail: rbjones@doctors.org.uk. Submitted for publication July 15, 2008; accepted in revised form April 1, 2009. 2156