Obinutuzumab versus rituximab in refractory membranous nephropathy: a single-center retrospective cohort study

BACKGROUND: Refractory membranous nephropathy (MN) remains challenging. We aim to compare the efficacy and safety of obinutuzumab versus rituximab in adults with refractory or relapsing MN, using a retrospective, single-center study design. METHODS: This retrospective, single-center cohort study was conducted at the Fifth Affiliated Hospital of Wenzhou Medical University from January 2022 to January 2025. Eleven patients received obinutuzumab, and twenty-two matched controls received rituximab after propensity score matching (1:2). Inclusion criteria were biopsy-confirmed primary MN, age between 18 and 80 years, and a diagnosis of refractory disease. The primary endpoints were a composite measure of treatment response (including partial remission [PR] and complete remission [CR]); secondary endpoints included immunological remission and safety. Kaplan-Meier analyses were used to estimate time to response and time to CR; log-rank tests compared groups. Multivariate Cox regression identified factors associated with response. RESULTS: Baseline characteristics were balanced. Obinutuzumab achieved higher overall response and CR rates (log-rank p = 0.0074 and p = 0.012, respectively). At 18 months, CR was 54.6% with obinutuzumab versus 9.1% with rituximab (p = 0.024). Obinutuzumab induced prolonged B cell depletion and faster attainment of immunological remission (anti-PLA2R < 14 RU/mL). Improvements in serum albumin and 24-hour proteinuria favored obinutuzumab at 6-12 months (p < 0.05). Safety was comparable between groups; adverse events were mostly infusion-related and manageable. Multivariate analysis showed that obinutuzumab independently predicted a better response (adjusted HR (95%CI) 2.86 (1.08 ~ 7.62); p < 0.05). CONCLUSIONS: In this preliminary retrospective analysis, obinutuzumab was associated with higher response rates than rituximab in refractory membranous nephropathy, with comparable safety.Nevertheless, given the small sample size and retrospective design, these findings should be interpreted as hypothesis-generating. Prospective randomized controlled trials are required to confirm these observations.