Rituximab, tacrolimus, cyclophosphamide and cyclosporin in primary membranous nephropathy with nephrotic syndrome: comparison of safety profiles, effect on remission rate, 24-h urinary total protein, serum albumin, and serum creatinine levels using network meta-analysis.

Objective: To compare the efficacy and safety of four immunosuppressive therapies, either alone or in combination, for primary membranous nephropathy through a network meta-analysis.

Methods: A literature search was conducted for randomized controlled trials (RCTs) of Cyclophosphamide (CTX), Cyclosporin (CsA), Tacrolimus (TAC), and Rituximab (RIT) in the treatment of primary membranous nephropathy. Two researchers independently screened articles, extracted data, and evaluated the quality. Outcome indicators included dichotomous variables and continuous variables, which were represented by risk ratios (RR) and mean differences (MD), respectively. Then, various interventions were ranked according to the surface under the cumulative ranking curve (SUCRA).

Results: A total of 21 randomized controlled trials (RCTs) were included, encompassing 1396 patients. In terms of the overall response rate (ORR), RIT+TAC was superior to CsA (RR = 0.15, 95% CI: 0.04, 0.54), CTX (RR = 0.09, 95% CI: 0.03, 0.31), and RIT (RR = 7.06, 95% CI: 2.29, 21.80). The SUCRA value of RIT+TAC was the highest, reaching 93.5%. Regarding the total 24-h urinary protein (24UTP), RIT+TAC was better than RIT (MD = 17.05, 95% CI: 6.49, 44.79), RIT+CTX (MD = 6.99, 95% CI: 2.55, 19.17), TAC (MD = 0.12, 95% CI: 0.07, 0.18), CsA (MD = 0.06, 95% CI: 0.00, 0.86), and CTX (MD = 0.05, 95% CI: 0.03, 0.10). The SUCRA value of RIT+TAC was the highest, at 99.4%. For serum albumin, RIT+CTX was superior to CTX (MD = 0.00, 95% CI: 0.00, 0.29), and the SUCRA value of RIT+CTX was the highest, at 76.7%. For serum creatinine (Scr), RIT+TAC was better than TAC (MD = 0.00, 95% CI: 0.00, 0.13), and CsA was better than TAC (MD = 7.86e+07, 95% CI: 3.65e+06, 1.69e+09). The SUCRA value of RIT+TAC was the highest, at 79.9%. In terms of the incidence of adverse reactions, CTX had a higher rate than RIT+CTX (RR = 11.12, 95% CI: 1.34, 92.15). The SUCRA value of RIT+CTX was the lowest, at 5.3%.

Conclusion: In terms of improving ORR, reducing 24UTP and lowering Scr, the RIT+TAC regimen may be the most optimal. Conversely, RIT+CTX demonstrated the best efficacy in improving ALB and also exhibited relatively better safety profile.