Objective To compare the clinical efficacy and safety of two regimens of rituximab (RTX) for idiopathic membranous nephropathy (IMN).

Methods A total of 79 IMN patients were recruited from December 01, 2019 to December 31, 2021. RTX two-dose regimen group (n=49): two infusions of 1g at 2-week intervals; if nephrotic albuminuria persisted during a 6-month follow-up, the regimen could be repeated once. RTX four-dose regimen group (n=30): four infusions of 375 mg/m² at 1-week intervals. Both groups had a combination of low-dose glucocorticoid. The differences of 24-hour urinary protein, serum albumin, blood creatinine, peripheral blood CD19⁺ cell count, anti-PLA2R antibody titer, disease remission rate and adverse reactions were compared between two groups before and at different timepoints post-treatment.

Results No significant inter-group differences existed in gender, age, body mass index, blood pressure, 24-hour urinary protein, serum albumin, blood creatinine, eGFR, anti-PLA2R antibody or peripheral blood CD19⁺ cell count pre-treatment (P>0.05). At Month 12, 24-hour urinary protein declined markedly in 2 groups as compared with pre-treatment (P<0.01); serum level of albumin spiked markedly as compared with pre-treatment (P<0.01). However, no significant inter-group difference existed in reduction of urinary protein and recovery of serum albumin post-treatment (P>0.05). In terms of serum creatinine, total renal function of 2 groups remained stable without statistical significance (P>0.05). Anti-PLA2R-Ab level declined markedly in two groups post-treatment as compared with pre-treatment and the difference was not statistically significant (P>0.05). In terms of disease remission, total effective rate reached 75.95% at Month 12 and clinical remission rate of RTX two-dose regimen group was significantly higher than that of RTX four-dose regimen group (85.71% vs 60%). And the difference was statistically significant (P<0.01). Meanwhile, recurrence rate was lower in RTX two-dose group than that in RTX four-dose group (18.37% vs 23.33%). No significant inter-group difference existed in adverse reactions (P>0.05).

Conclusion With a higher clinical remission rate without a higher incidence of adverse reactions, high-dose RTX regimen is more suitable for treating IMN. However, adverse reactions causing severe hypokalemia deserve greater attention.