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Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial.

Published version
Peer-reviewed

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Authors

Jones, Rachel B 
Specks, Ulrich 
Bond, Simon 

Abstract

OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier.

Description

Peer reviewed: True


Acknowledgements: The RITAZAREM trial is directed by the European Vasculitis Society and the Vasculitis Clinical Research Consortium (VCRC). The primary sponsor is Cambridge University Hospitals NHS Foundation Trust, and there are collaboration and data-sharing agreements with the University of Pennsylvania and the University of Miyazaki and Okayama University in Japan.


Funder: Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan

Keywords

B-lymphocytes, granulomatosis with polyangiitis, rituximab, systemic vasculitis, therapeutics, Humans, Azathioprine, Rituximab, Immunosuppressive Agents, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Recurrence, Remission Induction, Treatment Outcome, Cyclophosphamide, Antibodies, Antineutrophil Cytoplasmic

Journal Title

Ann Rheum Dis

Conference Name

Journal ISSN

0003-4967
1468-2060

Volume Title

Publisher

BMJ
Sponsorship
Arthritis Research Uk (None)