Induction and maintenance of remission with mycophenolate mofetil in ANCA-associated vasculitis: A systematic review and meta-analysis

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 (GPA) and microscopic polyangiitis (MPA)). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to May 5th, 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, five phase II and five III trials, 4 assessed remission-induction, 3 remission-maintenance, 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% CI: [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%-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 significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.