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.

1st Department of Internal Medicine Kyorin University School of Medicine Tokyo Japan

Allergy and Clinical Immunology Chiba University Chiba Japan

Cambridge Clinical Trials Unit Cambridge University Hospitals NHS Foundation Trust Cambridge UK

Hemovascular Medicine and Artificial Organs Faculty of Medicine University of Miyazaki Miyazaki Japan

Medicine Addenbrooke's Hospital Cambridge UK

Medicine Charles University Praha Czech Republic

Medicine Imperial College London London UK

Medicine McMaster University Hamilton Ontario Canada

Medicine Rheumatology University of Pittsburg Pittsburg Pennsylvania USA

Medicine Royal Brisbane and Women's Hospital Herston Queensland Australia

Medicine University of Cambridge Cambridge UK

Medicine University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

Medicine University of Pennsylvania Philadelphia Pennsylvania USA

Mount Sinai Hospital University of Toronto Toronto Ontario Canada

Nephrology Australian National University Medical School Canberra Australian Capital Territory Australia

Nephrology East Kent Hospitals University NHS Foundation Trust Canterbury UK

Nephrology Ipswich Hospital NHS Trust Ipswich UK

Nephrology Karolinska University Hospital and Karolinska Institute Stockholm Sweden

Nephrology Nottingham University Hospitals NHS Trust Nottingham UK

Nephrology Royal Adelaide Hospital Adelaide South Australia Australia

Nephrology South Tees Hospitals NHS Foundation Trust Middlesbrough UK

Nephrology University Hospitals of Leicester NHS Trust Leicester UK

Nephrology University of Birmingham Birmingham UK

Nephrology University of Leicester Leicester UK

NIHR Leeds Musculoskeletal Biomedical Research Unit Leeds Teaching Hospitals Trust Leeds UK

Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Science University of Oxford Oxford UK

Pulmonary Medicine Mayo Clinic Rochester Minnesota USA

Renal Medicine Addenbrooke's Hospital Cambridge UK

Rheumatic and Immunologic Diseases Cleveland Clinic Foundation Cleveland Ohio USA

Rheumatology Cedars Sinai Medical Center Los Angeles California USA

Rheumatology Dudley Group of Hospitals NHS Trust Dudley UK

Rheumatology Hospital for Special Surgery New York New York USA

Rheumatology Nottingham University Hospital Nottingham UK

Rheumatology Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

Rheumatology The University of Utah Salt Lake City Utah USA

Rheumatology University of Michigan Ann Arbor Michigan USA

Rheumatology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

Rheumatology University of Toronto Toronto Ontario Canada

The Clinical and Translational Research Center Kyoto Prefectural University of Medicine Kyoto Japan

UNC Kidney Center Division of Nephrology and Hypertension University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

Vasculitis and lupus clinic Cambridge University Hospitals NHS Foundation Trust Cambridge UK

Ann Intern Med. 2023 Aug;176(8):JC95. doi: 10.7326/J23-0057. PubMed

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ClinicalTrials.gov
NCT01697267