Obinutuzumab in Refractory Membranous Nephropathy: A Case Series

Abstract Rationale & Objective Membranous nephropathy (MN), recognized as an autoimmune kidney disease, responds well to anti-CD20 monoclonal antibodies. Obinutuzumab, a type Ⅱ humanized anti-CD20 and immunoglobulin G1 Fc-optimized monoclonal antibody, compared to rituximab, has demonstrated superior efficacy in B cell leukemia and lymphoma, especially in rituximab-resistant cases. However, the efficacy and safety of obinutuzumab in MN remain unclear. Study Design Retrospective cohort study. Setting & Participants A total of 18 patients who were diagnosed as MN and received obinutuzumab at our center, without secondary MN, undergoing dialysis, history of kidney transplantation, or infections requiring treatment. Exposure Obinutuzumab treatment. Outcomes Primary outcomes included remission rate, time to first remission, and first relapse-free survival time during the follow-up period. Analytical Approach Survival analysis was conducted with Cox proportional hazards models, Log-rank test, and Kaplan–Meier survival analysis. Results MN patients (median age 52.5 years, 83% males) received an average dose of 2.1 ± 0.8 g obinutuzumab during a median follow-up period of 13.6 months. During follow-up, 17 patients (94.4%) achieved remission, with 12 patients (66.7%) achieving partial remission (PR) and 5 patients (27.8%) achieving complete remission (CR). The median time to first remission and first relapse-free survival time was 2.7 (1.0, 6.1) months and 9.8 (2.6, 11.2) months, respectively. Of 12 patients with previous rituximab treatment, all achieved remission successfully, with 8 (66.7%) achieving PR and 4 (33.3%) achieving CR. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Limitations Limited or missing data, risks of selection bias, or recall bias; underestimated first relapse-free survival time due to limited follow-up period; unmonitored counts of CD19⁺ B cells and other lymphocyte subsets. Conclusions Obinutuzumab demonstrated promising efficacy and safety in inducing remission in MN, particularly in patients with an unsatisfactory response to rituximab.