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Obinutuzumab is a new generation monoclonal antibody targeting CD20 on the surface of B cells, with significantly enhanced efficiency of B cell depletion. Limit cases of membranous nephropathy (MN) treated with Obinutuzumab are reported in the literature. The present study aims to explore the efficiency and safety of Obinutuzumab for MN in a retrospectively cohort from China.
From October 2022 to April 2023 in the National Clinical Medical Research Center for Renal Diseases at Jinling Hospital, patients with biopsy-proven primary MN refractory to immunosuppressive therapies or with moderate to high risk received Obinutuzumab treatment were retrospectively analyzed. The standard induction regimen is Obinutuzumab 1g twice at an interval of two weeks. Immunological complete remission is defined as A-PLA2R<2RU/ml. B cell depletion is defined as CD20+cells<5/ul. Refractory MN refers to patients received immunosuppressive agents such as cyclophosphamide (CYC), calcineurin inhibitors (CNI), and rituximab (RTX) with or without glucocorticoid for more than 6 months but have not yet achieved remission.
23 MN patients including 20 males and 3 females was enrolled in the present study. 17 cases were refractory MN (4 cases refractory to CNIs and CYC, 3 cases refractory to RTX and CNI, 9 cases refractory to CNI, and 1 case refractory to CYC), and 6 patients was newly diagnosed MN with moderate to high risk. The mean proteinuria was 10.6g/24h and mean CD20+ cell count was 209/ul at baseline. At 2 weeks, 6 weeks, 3 months, and 6 months following the treatment with Obinutuzumab, the proportion of B cell depletion was 100%, 100%, 100%, and 91%, while the proportion of immunological complete remission was 10%, 57%, 78%, and 91%, respectively. Proteinuria was significantly decreased while albumin was significantly increased during the follow ups. Renal function remained stable. Compared with baseline, IgG was significantly increased at 6 months, while IgA and IgM presented with no significant changes. Renal remission rates at month 3rd and 6th were 52% and 74%, respectively. Among the six patients who did not respond at 6 months, 5 (83%) achieved complete immune response, and 4 (67%) experienced a decline over 50% in proteinuria. Three patients experienced moderate infusion reactions during their first administration of Obinutuzumab, two of who had history of allergic diseases previously. No patients experienced severe infection or progressed to end stage kidney disease within 6 months following treatment.
Obinutuzumab is safe and effective in the treatment of membranous nephropathy. Long duration of B cell depletion and high immunological remission rate may account for its remarkable efficiency.