A meta-analysis on the efficacy and safety of obinuzumab for membranous nephropathy

Background: The management of idiopathic membranous nephropathy (IMN) continues to be a significant challenge to date. A limited number of observational studies have compared Obinutuzumab’s (OBZ) therapeutic potential, with OBZ appearing to be more effective than rituximab (RTX) in achieving clinical remission. Objective: This study was designed to evaluate the effectiveness and safety profile of OBZ for IMN treatment. Design: Clinical studies regarding the application of OBZ for IMN were included, and the effector sizes were pooled by meta-analysis. Sensitivity analysis and subgroup analysis were adopted to evaluate the robustness and reliability of the findings. Data sources and methods: Several electronic databases were systematically searched for relevant studies. Effectors, including the rates of total remission (TR) and complete remission (CR), reported in these studies were extracted and pooled as non-comparative binary variables. The rates of immunologic remission, B-cell depletion, and adverse events (AEs) were recorded. Results: Among the studies retrieved in the initial search, 9 eligible studies with 344 participants were included in this meta-analysis. OBZ therapy increased the TR rates at 6 months (0.78 (0.71, 0.85)) and 12 months (0.88 (0.82, 0.93)) and improved the CR rates at 6 months (0.13 (0.03, 0.23)) and 12 months (0.27 (0.16, 0.39)) compared to RTX. No evident heterogeneity or publication bias was observed. The results persisted in the subgroup analysis in terms of OBZ, as the initial treatment for membranous nephropathy (MN), for refractory MN, or for RTX-refractory MN. Interestingly, OBZ treatment was linked to a greater probability of achieving TR than RTX treatment (At 6 months, odds ratio was 4.07 (1.94, 8.53)) and (At 12 months, odds ratio was 10.79 (3.38, 34.39)). OBZ therapy consistently led to a relatively high rate of immunological remission and effective B-cell clearance and did not increase the incidence of AEs or severe AEs. Conclusion: OBZ therapy is associated with improved clinical remission and might be an attractive option for patients with IMN, especially those with refractory or RTX-refractory IMN. High-quality clinical studies are, however, warranted to validate these results further. Trial registration: This study was registered as a meta-analysis in PROSPERO (Number: CRD42025635162).