Comparative efficacy and safety of rituximab, mycophenolate, methotrexate, and cyclophosphamide versus azathioprine as maintenance therapy in antineutrophil cytoplasmic antibody-associated vasculitis: A Bayesian network meta-analysis of randomized controlled trials.

Abstract

In this study we aimed to compare the effectiveness and safety of rituximab, mycophenolate mofetil (MMF), methotrexate (MTX), and cyclophosphamide (CYC) with azathioprine (AZA) for maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We searched MEDLINE, EMBASE, and Cochrane databases to retrieve randomized controlled trials (RCTs) examining the efficacy and safety of rituximab, MMF, MTX, CYC, and AZA for maintenance therapy in AAV patients. We applied a random-effects, meta-analytic model in all calculations. We performed a Bayesian fixed-effects network meta-analysis to combine direct and indirect evidence from RCTs. The primary effectiveness outcome was the number of patients who experienced relapse during the maintenance phase, while the primary safety outcome was the number of serious infections. Five RCTs including 667 patients were included. Rituximab demonstrated lower relapse rates than MMF (odds ratio (OR), 0.16; credible interval (CrI), 0.07-0.38). Surface under the cumulative ranking curve (SUCRA)-based likelihood rating revealed that rituximab had the probability of being the best relapse-lowering therapy, followed by CYC, MTX, AZA, and MMF. In SUCRA-based likelihood rating, rituximab showed the greatest probability of being the best major relapse-based therapy, followed by CYC, AZA, and MMF. MMF showed a lower risk of serious infection than MTX did (OR, 0.04, 95% CrI, 0.00-0.53). SUCRA-based rating probability revealed MMF was likely the safest treatment with the lowest incidence of serious infection, followed by CYC, AZA, rituximab, and MTX, although the difference was only significant between MMF and MTX. Rituximab may be an effective relapse-lowering, maintenance treatment for patients with AAV, and MMF showed the lowest rate of serious infections among the drugs investigated.