This study aimed to compare the clinical efficacy, safety, and immunologic responses between rituximab (RTX) plus glucocorticoids and cyclophosphamide (CTX) monotherapy in patients with primary membranous nephropathy (PMN). A total of 102 patients with biopsy-proven PMN treated at our center between January 2023 and January 2025 were retrospectively analyzed. Patients were divided into the RTX plus glucocorticoid group (RTX group, n = 52) and the CTX monotherapy group (CTX group, n = 50). Baseline characteristics were comparable between groups. Primary endpoints included clinical remission rates (complete + partial) at 6 and 12 months, time to remission, relapse rate and sustained remission, M-type phospholipase A 2 receptor (PLA 2 R) antibody clearance, safety events, and changes in renal function. At 6 months, the total remission rate was significantly higher in the RTX group than in the CTX group (73.1% vs 54.0%, P = .042); at 12 months, remission rates further increased to 84.6% and 66.0%, respectively ( P = .028). The median time to remission was shorter in the RTX group (3.1 vs 4.5 months, P = .011). Among responders, relapse occurred in 9.1% of RTX-treated patients versus 21.2% in the CTX group, with a significantly higher relapse-free survival in the RTX group ( P = .045). Among PLA 2 R-positive patients, the 12-month antibody clearance rate was higher with RTX (78.3% vs 56.0%, P = .035), and clinical remission was more frequent in antibody clearers than in non-clearers (91.2% vs 60.5%, P < .01). The overall incidence of adverse events was lower with RTX (13.5% vs 30.0%, P = .041), mainly consisting of mild to moderate, reversible reactions. Estimated glomerular filtration rate remained stable in both groups, and no patient progressed to end-stage renal disease. Rituximab combined with glucocorticoids significantly improved remission rates, shortened the time to response, and reduced relapse risk in patients with PMN. Clinical remission was closely associated with PLA 2 R antibody clearance. Compared with CTX, RTX demonstrated a superior safety profile and better tolerability, making it a safe, effective, and mechanistically precise immunological therapy. These findings provide new clinical evidence supporting RTX as a key component of individualized, precision treatment strategies for membranous nephropathy.
Lou et al. (Fri,) studied this question.