Obinutuzumab Compared to Cyclosporine with Steroids for the Treatment of Primary Membranous Nephropathy: A Propensity Score-Matched Analysis.

BACKGROUND: To compare the efficacy and safety profiles of obinutuzumab or cyclosporine combined with steroid in treating primary membranous nephropathy. METHODS: This retrospective study included patients with primary membranous nephropathy treated at Shanghai Ruijin Hospital between January 2020 and June 2023. Patients received either obinutuzumab or cyclosporine combined with corticosteroid and were followed for at least 24 months unless relapse or treatment failure occurred. Propensity score matching (PSM, ratio: 1:1) based on age, sex, degree of proteinuria, eGFR, serum albumin and PLA2R antibody was applied to pair patients receiving Obinutuzumab with those receiving cyclosporine combined with corticosteroid. The primary outcome was defined as the combination of partial remission and complete remission at 24 months. Logistic regression model and Kaplan-Meier curves were applied to compare the efficacy of two treatments. RESULTS: After PSM, 30 patients receiving obinutuzumab and 30 patients receiving cyclosporine with corticosteroid were included in the study. By 24 months, a higher proportion of patients in the obinutuzumab group reached the primary endpoints compared to those treated with cyclosporine combined with corticosteroid. (Obinutuzumab vs. Cyclosporine: 86 % vs. 54 %, P=0.01; HR:5.42, 95%CI:1.49-19.69, P=0.01). Relapses of nephrotic syndrome were less frequent in the obinutuzumab group than in the cyclosporine group (Obinutuzumab vs. Cyclosporine: 15% vs. 52%, P=0.01; HR:0.16, 95%CI: 0.04-0.60, P=0.01). Obinutuzumab induced a faster immunologic remission at 6 months (Obinutuzumab vs. Cyclosporine: 91% vs. 59%, P<0.01; HR: 7.22, 95% CI: 1.40-37.25, P=0.02) and maintained a better persistent immunologic remission at 24 months [Obinutuzumab vs. Cyclosporine: 95% vs. 45%, P<0.01; HR: 24.44, 95%CI: 2.73-219.09, P<0.01]. Both treatment regimens were generally well-tolerated. The incidence of infection was lower in the obinutuzumab group than in the cyclosporine combined with corticosteroid group (Obinutuzumab vs. Cyclosporine: 23% vs. 50%, P=0.03). CONCLUSIONS: Our study demonstrated that obinutuzumab is associated with higher remission rates at 24 months, faster immunological remission and less infections than cyclosporine combined with corticosteroids in the treatment of PMN.