What question did this study set out to answer?

To compare the efficacy and safety of rituximab and cyclophosphamide combined with steroids in treating primary membranous nephropathy.

March 18, 2026Open Access

Comparative efficacy and safety of rituximab versus cyclophosphamide with steroids in primary membranous nephropathy: a systematic review and meta-analysis

Key Points

To compare the efficacy and safety of rituximab and cyclophosphamide combined with steroids in treating primary membranous nephropathy.
Conducted a systematic review and meta-analysis of studies until November 2025.
Included randomized controlled trials and cohort studies evaluating the treatments in PMN patients.
Analyzed primary outcomes of complete and partial remission, and secondary outcomes of relapse rates and adverse events.
Eleven studies with 1068 patients were included in the analysis.
Rituximab showed similar efficacy to cyclophosphamide with steroids for complete and partial remission at 6 and 12 months.
No significant differences were observed in adverse events or serious adverse events between both treatment groups.

Abstract

Abstract Background Primary membranous nephropathy (PMN) is a leading cause of nephrotic syndrome in adults. In some patients, PMN can be severe or continue to worsen even after 6 months of supportive treatment. Rituximab and cyclophosphamide with steroids are used to treat moderate-risk or high-risk PMN patients, but the comparative efficacy and safety of rituximab and cyclophosphamide with steroids in patients with PMN remains debated. Methods We searched PubMed, Embase and the Cochrane Library for the time period through November 2025 to identify randomized controlled trials and cohort studies that evaluated rituximab compared with cyclophosphamide for the treatment of PMN. The primary outcomes were complete remission (CR), partial remission (PR), and total remission (TR = PR+CR). The secondary outcomes included the relapse rate, adverse events (AEs), and serious adverse events (SAEs). The random effects model (DerSimonian–Laird method) was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Results Eleven studies ( N = 1068) were eligible for final inclusion. Rituximab showed similar efficacy to cyclophosphamide with steroids in inducing complete or partial remission at 6 months (RR, 0.82; 95% CI, 0.60–1.10; p = 0.19; I 2 = 0%) and 12 months (RR, 0.85; 95% CI, 0.66–1.10; p = 0.21; I 2 = 0%). Similarly, rates of CR were comparable between the two treatment groups at 6 months (RR, 0.97; 95% CI, 0.33–2.89; p = 0.95; I 2 = 0%) and 12 months (RR, 0.54; 95% CI, 0.26–1.12; p = 0.10; I 2 = 0%). There were no significant differences in the incidence of AEs or SAEs between RTX and cyclophosphamide with steroids. The RRs were 0.76 (95% CI, 0.46–1.28; p = 0.30; I 2 = 51%) and 1.00 (95% CI, 0.50–2.00; p = 1.00; I 2 = 0%), respectively. Conclusions The current limited evidence suggests that RTX treatment has comparable efficacy and safety to cyclophosphamide with steroids in PMN patients at moderate risk or high risk. Further large-scale, longer follow-up, well-designed RCTs on head-to-head comparisons of the safety and efficacy of rituximab versus cyclophosphamide with steroids are urgently needed.

Bookmark

View Full Paper