Optimized RTX strategy plus structured glucocorticoid tapering for primary membranous nephropathy: a multicenter...

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.

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/m² 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/m² 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.

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.

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.