Comparison of Obinutuzumab and Rituximab for Treating Primary Membranous Nephropathy

Key Points Obinutuzumab induced more remission than rituximab at 12 months in patients with primary membranous nephropathy. Obinutuzumab shared a similar safety profile as rituximab in patients with primary membranous nephropathy. Background This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy (MN). Methods Patients with primary MN who had urine protein ≥3.5 g/24 hours and eGFR ≥30 ml/min per 1.73 m 2 despite 6 months of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and treatment with obinutuzumab or rituximab were included and matched by propensity score (ratio: 1:2) on the basis of age, sex, urine protein, eGFR, and titers of Anti-Phospholipase A2 receptor (PLA2R) antibody. The primary outcome was defined as a combination of partial or complete remission at 12 months. Logistic regression models, Kaplan–Meier curves, and absolute risk differences were used to compare the therapeutic effectiveness and safety profiles of obinutuzumab and rituximab. Results Sixty-three patients with primary MN were included in the study, with 21 patients receiving obinutuzumab and 42 patients receiving rituximab. At 12 months, the primary outcome was achieved in 20 of 21 patients in the obinutuzumab group and 28 of 42 patients in the rituximab group (obinutuzumab versus rituximab: 95% versus 67%; odds ratio, 10.00; 95% confidence intervals, 1.21 to 82.35; P = 0.03). Moreover, patients in the obinutuzumab group acquired more complete remission (obinutuzumab versus rituximab: 38% versus 14%; odds ratio, 3.69; 95% confidence interval, 1.08 to 12.68; P = 0.04). In PLA2R-associated primary MN subgroup analyses, patients in the obinutuzumab group sustained lower CD19 B-cell counts (CD19 B-cell counts: median [interquartile range] 0 [0–6] cells/ μ l versus 20 [3–58] cells/ μ l, P = 0.002) and were more prone to achieve immunological remission (defined as PLA2R antibody <2 RU/ml) at 6 months (obinutuzumab versus rituximab: 92% [12 out of 13] versus 64% [16 out of 25], P = 0.06) than rituximab. Both treatment regimens were well tolerated. Conclusions Our study demonstrated that obinutuzumab is associated with higher odds of clinical remission compared with rituximab at 12 months, which may be due to higher immunological remission at 6 months with a similar safety profile in patients with primary MN.