OBJECTIVES: Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV. METHODS: We conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR <15 mL/min were excluded from the study. RESULTS: At baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI -7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3). CONCLUSION: MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate. TRIAL REGISTRATION NUMBER: NCT00414128.

Cambridge Clinical Trials Unit Addenbrooke's Hospital Cambridge UK

Department of Autoimmune Diseases Hospital Clinic University of Barcelona Institut d'investigacions Biomediques August Pi i Sunyer Barcelona Spain

Department of Biomedical Experimental and Clinical Sciences 'Mario Serio' University of Firenze Firenze Italy

Department of General Internal Medicine University Hospitals Leuven Leuven Belgium

Department of Medicine University of Auckland Auckland New Zealand

Department of Nephrology Charles University and General University Hospital Prague Czech Republic

Department of Nephrology Fundació Puigvert Barcelona Spain

Department of Paediatric Rheumatology Great Ormond Street Hospital NHS Foundation Trust London UK

Department of Paediatric Rheumatology University College London Great Ormond Street Institute of Child Health London UK

Department of Renal Medicine Addenbrooke's Hospital Cambridge UK

Department of Renal Medicine Canberra Hospital Canberra Australian Capital Territory Australia

Department of Renal Medicine Karolinska University Hospital Stockholm Sweden

Department of Renal Medicine Royal Adelaide Hospital Adelaide South Australia Australia

Department of Rheumatology Nottingham University Hospitals NHS Trust Nottingham UK

Departments of Medicine and Health Research Methods Evidence and Impact McMaster University Hamilton Ontario Canada

Institute of Clinical Sciences University of Birmingham Birmingham UK

Nephrology and Dialysis Unit Meyer Children's University Hospital Firenze Italy

Renal Service Waitemata District Health Board Auckland New Zealand

School of Clinical Medicine University of Cambridge Cambridge UK

Ann Rheum Dis. 2020 May;79(5):e58. doi: 10.1136/annrheumdis-2019-215254. PubMed

Ann Rheum Dis. 2020 May;79(5):e57. doi: 10.1136/annrheumdis-2019-215241. PubMed

Ann Rheum Dis. 2020 Aug;79(8):e100. doi: 10.1136/annrheumdis-2019-215647. PubMed

Ann Rheum Dis. 2020 Aug;79(8):e101. doi: 10.1136/annrheumdis-2019-215658. PubMed

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NCT00414128