Obinutuzumab is effective for the treatment of rituximab-refractory PLA2R-associated membranous nephropathy.

Background: Clinical experience with obinutuzumab in patients with rituximab-refractory phospholipase A2 receptor (PLA2R)-associated membranous nephropathy remains limited. This study aimed to evaluate the efficacy and safety of obinutuzumab in treating patients with rituximab-refractory PLA2R-associated membranous nephropathy.

Methods: A single-center retrospective study was conducted on 20 patients with rituximab-refractory PLA2R-associated membranous nephropathy who received two doses of 1 g obinutuzumab, administered 2 weeks apart. At 6 months, patients with urinary protein levels exceeding 3.5 g/d received an additional dose of 1-2 g obinutuzumab. The primary clinical outcome was a composite measure of complete or partial remission during follow-up. Continuous secondary outcomes included 24-hour urinary protein, serum albumin, serum creatinine, serum anti-PLA2R levels, and CD19 B-cell counts at the time of obinutuzumab infusion, at 3 months, and at the last visit.

Results: A total of 20 patients with clinical manifestations of nephrotic syndrome were included in this study, with a median follow-up period of 9 months. The mean age of the patients was 46.25 ± 13.05 years. At a median follow-up of 4.50 months (3.00-8.25 months) after obinutuzumab therapy, remission was achieved in 16 patients. Two patients (10%) achieved complete remission, while 14 (70%) attained partial remission. At baseline, 16 out of 20 patients tested positive for serum anti-PLA2R antibodies, and immunological remission was observed in 11 of these 16 patients during follow-up. All patients experienced B-lymphocyte depletion within 1 month after receiving obinutuzumab infusion and maintained this depletion at 3 months. B-lymphocyte reconstitution was noted in 4 out of 20 patients (20%) at 6 months. No patients experienced fatal adverse events.

Conclusion: Obinutuzumab mainly induces short-term partial remissions in patients with rituximab-refractory primary membranous nephropathy, which may be related to the short follow-up period. However, this study demonstrates that obinutuzumab is an effective and safe treatment for rituximab-refractory PLA2R-associated membranous nephropathy.