Efficacy and safety of tacrolimus monotherapy versus cyclophosphamide-corticosteroid combination therapy for idiopathic membranous nephropathy: A meta-analysis.

Objective: The objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus cyclophosphamide (CTX)-corticosteroid combination therapy in idiopathic membranous nephropathy (IMN) patients.

Methods: Databases including the PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from inception to October 20, 2020. Eligible studies comparing TAC monotherapy and CTX-corticosteroid combination therapy in IMN patients were included. Data were analyzed using Review Manager Version 5.3.

Results: Nine studies were included in the meta-analysis. One randomized controlled trial and eight cohort studies involving 442 patients were identified. Compared with CTX-corticosteroid combination therapy for IMN, TAC monotherapy had higher complete remission (CR) at month 6 (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.35-3.50, P < .01). The 2 therapeutic regimens had similar partial remission (OR 0.69, 95% CI 0.45-1.04, P = .08), total remission (OR 1.38, 95% CI 0.85-2.23, P = 0.19) at month 6, and similar CR (OR 1.64, 95% CI 0.84-3.19, P = .15), partial remission (OR 0.71, 95% CI 0.37-1.38, P = 0.31), and total remission (OR 1.29, 95% CI 0.55-3.01, P = .56) after 1 year. The relapse rate of the TAC group was higher than that of the CTX group, but the difference was not statistically significant (OR 1.85, 95% CI 0.75-4.53, P = .18). There was no difference between the 2 therapeutic regimens concerning glucose intolerance (OR 1.15, 95% CI 0.61-2.14, P = .67), acute renal failure (OR 1.14, 95% CI 0.39-3.33, P = .81), or tremors (OR 4.39, 95% CI 0.75-25.67, P = .10). Incidences of gastrointestinal symptoms (OR 0.29, 95% CI 0.10-0.79, P = .02), infection (OR 0.18, 95% CI 0.08-0.39, P < 0.01), leukopenia (OR 0.14, 95% CI 0.04-0.51, P < .01), and abnormal aminotransferase (OR 0.31, 95% CI 0.13-0.77, P = .01) in the TAC group were all lower than those in the CTX group. Subgroup analysis showed that there was no significant difference between the TAC group and the CTX combined with corticosteroid 0.8 to 1 mg/kg/day group concerning CR at month 6 (P > .05). There was no significant difference between the TAC group and the CTX combined with corticosteroid 0.5 mg/kg/day group concerning abnormal aminotransferase (P > .05).

Conclusion: TAC monotherapy is comparable to CTX-corticosteroid combination therapy for renal remission in IMN patients. TAC monotherapy had a higher CR in the early stage and had fewer drug-related adverse effects. The relapse rate of TAC monotherapy was higher than that of CTX-corticosteroid combination therapy, but the difference was not significant.