Efficacy and safety of low- versus high-dose glucocorticoid regimens for induction of remission of anti-neutrophil cytoplasm antibody-associated vasculitis: a systematic review and meta-analysis

Abstract

Objective: Glucocorticoids (GCs) remain a cornerstone of the initial management of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but have several dose-dependent side effects, in particular infections. The optimal dosing and tapering of oral GCs for remission induction are unknown. A systematic review and meta-analysis was undertaken to determine the efficacy and safety of low- versus high-dose GC regimens. Method: A systematic search of MEDLINE, Embase, and PubMed databases was conducted. Clinical studies using a GC-based induction protocol were selected. A daily dose of 0.5 mg/kg or < 30 mg/day oral prednisolone equivalent by the start of week 4 of the induction tapering schedule marked the threshold between high- and low-dose GCs. Risk ratios (RRs) were calculated by the random effects model for outcomes of remission and infection. Relapse events were summarized using risk differences with 95% confidence intervals (CIs). Results: In total, 1145 participants were included in three randomized controlled trials and two observational studies, of whom 543 were assigned to the low-dose GC group and 602 to the high-dose GC group. A low-dose GC regimen was non-inferior to high-dose GCs with respect to outcomes of remission (RR 0.98, 95% CI 0.95–1.02, p = 0.37; I2 = 0%) and relapse (risk difference 0.03, 95% CI −0.01 to 0.06, p = 0.15; I2 = 12%), while significantly reducing the incidence of infection (RR 0.60, 95% CI 0.39–0.91, p = 0.02; I2 = 65%). Conclusion: Studies with low-dose GC regimens in AAV are associated with fewer infections while obtaining equivalent efficacy.