Efficacy and safety of obinutuzumab in patients with primary membranous nephropathy: a focus on refractory and rituximab-resistant patients.

BACKGROUND

There has been an annual rise in the incidence of primary membranous nephropathy (PMN), a common pathological type of nephrotic syndrome (NS). Obinutuzumab is a humanised, glycosylated, type II anti-CD20 monoclonal antibody. Characterised by its enhanced B-cell depletion capability compared with rituximab (RTX), obinutuzumab has demonstrated promising efficacy in the treatment of membranous nephropathy.

OBJECTIVE

This study aimed to investigate the efficacy and safety of obinutuzumab in treating various subtypes of PMN.

METHODS

A total of 94 PMN patients with NS were enrolled in this study. Based on their treatment history before receiving obinutuzumab, the patients were categorised into the Initial therapy group (group A, n=32), the Refractory group (group B, n=32), and the Remedial therapy group (group C, n=30). The efficacy and safety of obinutuzumab treatment after a 24-month follow-up period were observed and analysed in each group. The primary endpoint was the clinical remission rate (complete remission + partial remission) at 24 months, and the secondary endpoints were treatment safety and the incidence of treatment-emergent adverse events.

RESULTS

Following 24 months of obinutuzumab therapy, 95.74% (90/94) of the PMN patients achieved clinical remission, with 28.72% (27/94) reaching complete remission (CR) and 67.02% (63/94) achieving partial remission (PR). The Initial therapy group (group A) achieved a 100% (32/32) clinical remission rate: 37.5% (12/32) attained CR, and 62.5% (20/32) attained PR. The Refractory group (group B) achieved a 96.88% (31/32) clinical remission rate: 25% (8/32) attained CR, and 71.88% (23/32) attained PR. The Remedial therapy group (group C) achieved a 90% (27/30) clinical remission rate: 23.33% (7/30) attained CR, and 66.67% (20/30) attained PR. All 63 anti-PLA2R antibody-positive (>20 U/mL) patients and 16 anti-PLA2R antibody negativity but no immunological remission (2-20 U/mL) patients demonstrated declining antibody levels following obinutuzumab therapy, and 68.4% (54/79) attained complete immunological remission (<2 U/mL).

CONCLUSION

Obinutuzumab demonstrates high clinical remission rates and acceptable safety in PMN patients, with good efficacy even in refractory and RTX-resistant patients.