Efficacy and safety of modified-dose obinutuzumab in the treatment of refractory membranous nephropathy

Introduction Primary membranous nephropathy (MN) is an autoimmune kidney disease, and the main autoantibody is directed against the M-type phospholipase A2 receptor (PLA2R). Approximately 20-40% of patients with MN do not respond to standard immunosuppressive therapy, termed refractory MN. Previous studies suggest obinutuzumab’s efficacy in refractory MN, but the optimal dosing regimen remains undefined. Methods This single-center retrospective study investigated the efficacy and safety of a B-cell reconstitution-guided regimen of obinutuzumab in patients with refractory MN. All patients were followed at 3-month intervals for up to 18 months. The primary outcome was a composite of complete or partial remission. The secondary outcomes included complete remission, B-cell depletion, immunological remission, and safety profiles. Results A total of 33 patients with refractory MN were included (81.8% were rituximab-refractory), with a mean age of 46.1 ± 12.1 years. At baseline, these patients had a mean 24-hour urinary protein of 6.7 ± 4.9 g, a mean serum albumin of 30.0 ± 8.3 g/L, and positive anti-PLA2R in 19 (57.6%) cases. The median total obinutuzumab dose was 2 g (IQR: 2-3). Following treatment, the cumulative remission rate during the 18-month follow-up period reached 84.8%. B cells were depleted in all patients at month 3, and the median duration of sustained B-cell depletion was 12 months (95% CI: 9.5-14.5). Among the 19 anti-PLA2R-positive patients, 84.2% achieved immunological remission at month 18. No patients experienced severe adverse events. Conclusion This study demonstrates that B-cell reconstitution-guided modified-dose obinutuzumab is associated with favorable efficacy and a safety profile in refractory MN. The individualized strategy minimized drug exposure while maintaining efficacy, but the conclusions warrant further validation in controlled studies.