Optimized RTX strategy plus structured glucocorticoid tapering for primary membranous nephropathy: a multicenter propensity score-matched cohort study

Background Standard rituximab (RTX) regimens for primary membranous nephropathy (PMN) may result in subtherapeutic RTX exposure within 2–3 months due to altered pharmacokinetics, potentially contributing to delayed remission, incomplete immunologic control, and relapse. We evaluated whether an exposure-optimized RTX strategy combined with structured glucocorticoid tapering was associated with improved clinical and immunologic outcomes in PMN. Methods This multicenter retrospective study included 182 PMN patients with nephrotic syndrome (2020–2025). After 1:2 propensity score matching, 75 patients were analyzed: an exposure-optimized strategy group (RTX 375 mg/m 2 on days 1, 15, 30, and 120 with structured prednisone tapering, with subsequent TDM-guided redosing when RTX <2 μg/mL) versus standard RTX (RTX 375 mg/m 2 weekly ×4 weeks). Median follow-up time was 17.0 (IQR: 12.5–25.6) and 14.8 (IQR: 12.0–27.1) months for GC/MRTX and SRTX groups, respectively. Primary endpoint: complete remission (CR; proteinuria <0.3 g/24 h). Secondary endpoints: near-CR (NCR; ≥80% proteinuria reduction), complete immunological remission (anti-PLA2R < 2 RU/mL), and relapse. Results At 6 months, the GC/MRTX group had higher RTX concentrations (median 7.46 vs. 0.07 μg/mL, p = 0.020) and a higher proportion of patients with RTX concentrations ≥2 μg/mL (60.0% vs. 21.1%, p = 0.022). Anti-RTX antibodies were detected only in the SRTX group (11%). At 12 months, GC/MRTX was associated with higher CR (64.0% vs. 22.0%, p < 0.001), higher complete immunological remission (80% vs. 42%, p = 0.002), and shorter time to CR (9.0 vs. 18.4 months, p < 0.001). NCR at 12 months was 88.0% versus 70.0% (p = 0.085). Over follow-up, GC/MRTX showed higher cumulative CR (p < 0.001) and NCR (p = 0.036) and lower relapse (0% vs. 18.4%, p = 0.026). In refractory PMN (n = 51), GC/MRTX achieved higher 12-month CR (52.63% vs. 18.75%, p = 0.012) and complete immunological remission (89.47% vs. 34.38%, p = 0.001). Safety profiles were comparable. Conclusion In this propensity score–matched multicenter cohort, an exposure-optimized strategy combining interval RTX dosing, structured glucocorticoid tapering, and TDM-guided redosing was associated with higher and earlier remission, deeper immunologic response, and lower relapse compared with the standard RTX monotherapy.