Immunosuppressive therapies for the maintenance treatment of proliferative lupus nephritis: A systematic review and network metaanalysis

Abstract

Objective. To determine the most effective immunosuppressive therapy for the longterm management of proliferative lupus nephritis (PLN) based on the outcome of renal failure. Methods.A systematic review of randomized controlled trials (RCT) was conducted. MEDLINE and EMBASE were searched. RCT designed to examine the maintenance treatment effectiveness of immunosuppressive agents for PLN were included. A Bayesian network metaanalysis of 2-arm and 3-arm trials was used. A skeptical prior assumption was used in sensitivity analysis. Four immunosuppressive agents were evaluated: cyclophosphamide (CYC), azathioprine (AZA), mycophenolate mofetil (MMF), and prednisone alone. The outcome of interest was renal failure during the study period, defined by serum creatinine (sCr) > 256 μmol/l, doubling of sCr from baseline, and/or endstage renal disease. Results. The OR (95% credible interval) of developing renal failure at 2-3 years was 0.72 (0.11, 4.49) for AZA versus CYC, 0.32 (0.04, 2.25) for MMF versus CYC, 2.40 (0.22, 36.94) for prednisone alone versus CYC, and 0.45 (0.11, 1.48) for MMF versus AZA. The probability (95% credible interval) of developing renal failure at 2 years as expected for each agent was 6% (0.7%, 24%) for MMF, 12% (2%, 37%) for AZA, 16% (5%, 33%) for CYC, and 31% (5%, 81%) for prednisone alone. After applying a skeptical prior in the Bayesian analysis, there was no evidence of benefit for 1 therapy over another. Conclusion. Although the data suggest that MMF may be superior to other treatments for the maintenance treatment of PLN, the evidence is not conclusive.