BACKGROUND: Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. METHODS: Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. RESULTS: From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. CONCLUSIONS: In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

College of Medicine Gyeongsang National University Jinju Republic of Korea

Department of Biomedical Experimental and Clinical Sciences 'Mario Serio' University of Firenze and Nephrology Unit Meyer Children's Hospital Firenze Italy

Department of Medicine University of Cambridge Cambridge UK

Department of Nephrology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czechia

Department of Pathology University of Iowa IA City IA USA

Department of Pediatrics Yonsei University College of Medicine Seoul Republic of Korea

Division of Nephrology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USA

Evidence Based Practice Center Mayo Clinic Rochester MN USA

Korea Disease Control and Prevention Agency Division of Rare Disease Management Cheongju si Republic of Korea

Mayo Clinic Libraries Mayo Clinic Rochester MN USA

Reference Center in Complex Glomerular Disease of the National Health System Barcelona Spain

Santa Chiara Regional Hospital and Department of Cellular Computational and Integrative Biology University of Trento Rheumatology Trento Italy

Tareev Clinic of Internal Diseases Sechenov 1st Moscow State Medical University Moscow Russia

Vasculitis and Lupus Clinic Addenbrooke's Hospital Cambridge University Hospitals Cambridge UK

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Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations