A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis.
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 Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%).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.


CONCLUSIONS
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.
Jones
Rachel B
RB
Renal Unit, Addenbrooke's Hospital, Cambridge, UK. rbjones@doctors.org.uk
Ferraro
Alastair J
AJ
Chaudhry
Afzal N
AN
Brogan
Paul
P
Salama
Alan D
AD
Smith
Kenneth G C
KG
Savage
Caroline O S
CO
Jayne
David R W
DR
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab; D055502:Secondary Prevention; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology*; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; D000069283:Rituximab