Background Tacrolimus, mycophenolate mofetil (MMF), and azathioprine (AZA) have all shown considerable effectiveness as maintenance therapy for lupus nephritis in randomized controlled trials (RCTs), but their relative efficacy and safety in patients with lupus nephritis are still unknown. The objective of this research was to compare the relative effectiveness and safety of tacrolimus, MMF, and AZA as maintenance therapies for lupus nephritis.

Methods RCTs examining the efficacy and safety of tacrolimus, MMF, and AZA as maintenance therapies in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine the direct and indirect evidence from RCTs.

Results Nine RCTs comprising 815 patients were included in the study. Although the difference was not statistically significant, MMF showed a trend toward a lower relapse rate compared with AZA (OR 0.73, 95% CrI 0.44 – 1.30). Similarly, tacrolimus showed a trend toward a lower relapse rate compared with AZA (OR 0.92, 95% CrI 0.24 – 2.84). Ranking probability based on the surface under the cumulative ranking curve indicated that MMF had the highest probability of being the best treatment based on the relapse rate, followed by tacrolimus and AZA. The incidence of leukopenia in the tacrolimus and MMF groups was significantly lower than that in the AZA group (OR 0.11, 95% CrI 0.02 – 0.56; OR 0.12, 95% CrI 0.03 – 0.32). Fewer patients with infections were observed in the MMF group than in the AZA group, although the difference was not statistically significant. The analysis of withdrawal due to adverse events showed a similar pattern.

Conclusions Lower relapse rates combined with a more favorable safety profile suggest that tacrolimus and MMF are superior to AZA as maintenance treatments in lupus nephritis patients.