Obinutuzumab Versus Rituximab for the Treatment of Primary Membranous Nephropathy: A Systematic Review and Meta-Analysis

<b>Background:</b> The benefit of specific B cell-targeted therapy in primary membranous nephropathy has been consistently demonstrated and is part of guideline-directed therapy. Though effective, Rituximab displays a highly variable response rate possibly owing to incomplete peripheral B cell depletion. Obinutuzumab is a second-generation anti-CD20 antibody which offers greater sustained peripheral B cell depletion and thus may result in improved clinical effect. This meta-analysis compares clinical efficacy of Obinutuzumab with Rituximab for the treatment of primary membranous nephropathy. <b>Methods:</b> A comprehensive search of PubMed, EMBASE, and Google Scholar was conducted on 10 October 2025. The search identified all studies which directly compared results of Obinutuzumab with Rituximab in the treatment of primary membranous nephropathy. Risk of bias was assessed using the Cochrane ROBINS-I tool. Data extraction and statistical analysis were performed using RevMan 5.1 software, assessing heterogeneity with the I² statistic. <b>Results:</b> Ultimately, three retrospective studies including a total of 161 participants were analyzed. The pooled estimated odds ratio for total clinical remission at 6 months was 2.84 (95% CI [1.42-5.69], <i>p</i> = 0.003, I² = 0%), and at 12 months was 12.25 ([95% CI 2.67-56.28]), <i>p</i> = 0.001, I² = 0%). The pooled estimated odds ratio for complete clinical remission at 6 months was 1.78 (95% CI [0.25-12.63], <i>p</i> = 0.57, I² = 0%) at 12 months was 4.12 (95% CI [1.36-12.48], <i>p</i> = 0.01, I² = 0%). The pooled estimated odds ratio for immunologic remission at 6 months was 6.18 (95% CI [1.57-24.39], <i>p</i> = 0.009, I² = 58%), and at 12 months was 5.56 (95% CI [1.50-20.64], <i>p</i> = 0.01, I² = 0%). The pooled estimated odds ratio for peripheral B cell depletion at 6 months was 3.91 (95% CI [0.99-15.40], <i>p</i> = 0.05, I² = 25%). <b>Discussion:</b> Obinutuzumab signals improvement in clinically relevant end points when compared with Rituximab for the treatment of primary membranous nephropathy but will require confirmation with head-to-head prospective data. The main limitations of this study include small sample sizes, geographic restriction, and retrospective design of the studies resulting in reduced generalizability. <b>Other:</b> There was no funding for this study. This review has been registered with PROSPERO (ID 1218735).