Obinutuzumab versus rituximab for the treatment of refractory primary membranous nephropathy

BACKGROUND: Rituximab has been shown effective in patients with primary membranous nephropathy refractory to glucocorticoids plus cyclophosphamide (GC + CTX) or calcineurin inhibitors (CNIs), but the response rates remain limited. Compared with rituximab, obinutuzumab is a humanized anti-CD20 monoclonal antibody with greater B-cell depletion capacity. This study was performed to investigate the effectiveness of obinutuzumab compared with rituximab in treating patients with refractory primary membranous nephropathy. METHODS: A retrospective study was conducted at Huashan Hospital, Fudan University between 1 January 2015 and 31 July 2024, and included adult patients with primary membranous nephropathy who met the following criteria: (i) resistance to GC + CTX and/or CNI regimens, (ii) dependence on CNIs or (iii) relapse within 1 year after CTX discontinuation. The patients subsequently received either obinutuzumab or rituximab. The primary endpoint was treatment response, which was defined as overall remission of nephrotic syndrome with no need for rescue therapy after obinutuzumab versus rituximab treatment. The secondary measures included immunological remission and safety profiles. RESULTS: Among the 51 participants, 20 received obinutuzumab and 31 received rituximab. The response rate was significantly greater in patients receiving obinutuzumab than in those receiving rituximab (90.0% vs 38.7%, P < .001) during a follow-up period of 24 interquartile range (IQR) 10-34 months. Cox proportional hazards survival regression analysis also revealed the superior effectiveness of obinutuzumab (P < .001). Immunological remission rates were higher in patients receiving obinutuzumab at both 3 months (75.0% vs 20.0%, P < .001) and 6 months (87.5% vs 21.4%, P < .001). The safety profiles of the two treatments were comparable. Among the 19 non-responders treated with rituximab, 10 subsequently received obinutuzumab, and 8 achieved remission during a follow-up period of 20.0 (IQR 18.5-22.3) months. CONCLUSION: This retrospective study suggests that obinutuzumab is an effective treatment option for patients with primary membranous nephropathy refractory to GC + CTX, CNI and rituximab regimens.