Relative efficacy and safety of tacrolimus, mycophenolate mofetil, and cyclophosphamide as induction therapy for lupus nephritis: a Bayesian network meta-analysis of randomized controlled trials

Abstract

Aims: This study aimed to assess the relative efficacy and safety of tacrolimus, mycophenolate mofetil (MMF) and cyclophosphamide (CYC) as induction therapy for lupus nephritis.

Methods: Randomized controlled trials (RCTs) examining the efficacy and safety of tacrolimus, MMF and CYC for induction therapy in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs.

Results: Nine RCTs including 972 patients met the inclusion criteria and pair-wise comparisons were performed, including 11 direct comparisons. Tacrolimus showed a significantly higher overall response rate (complete remission plus partial remission) than CYC (OR 2.35, 95% confidence interval (CI) 1.03-5.45), and was more efficacious than MMF (OR 1.60, 95% CI 0.70-3.57). MMF was superior to CYC in terms of overall response (OR 1.45, 95% CI 0.96-2.42). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tacrolimus had the highest probability of being the best treatment for achieving the overall response (SUCRA = 0.9321), followed by MMF (SUCRA = 0.5385) and CYC (SUCRA = 0.0294). In terms of safety, tacrolimus showed the highest probability of decreasing the risk of serious infections (SUCRA = 0.9253), followed by MMF (SUCRA = 0.4027) and CYC (SUCRA = 0.1720).

Conclusions: Tacrolimus was the most efficacious induction treatment for patients with lupus nephritis, and had the highest probability of decreasing the risk of serious infections. Higher remission rates combined with a more favorable safety profile suggest that MMF is superior to CYC as induction treatment in these patients.

Keywords: CYC; MMF; Tacrolimus; lupus nephritis; network meta-analysis.