Li Xue-Qi, Liu Yang, Cai Ze-Yu, Lv Tie-Gang, Hao Jian
Department of Medicine, Division of Nephrology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, 010050, China.
Department of Medicine, Division of Radiology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, 010050, People's Republic of China.
Drug Des Devel Ther. 2025 Jul 11;19:5961-5972. doi: 10.2147/DDDT.S527661. eCollection 2025.
Membranous nephropathy (MN) can cause nephrotic syndrome. B cells contribute to MN, but available treatments are often inadequate. We addressed this treatment gap by analyzing the effect of obinutuzumab in patients with primary MN (PMN).
Forty-seven PMN patients were followed for six months, with 25 receiving obinutuzumab and 22 (control) receiving rituximab. Treatment response was assessed by 24-h urine total protein (24-h UTP), serum albumin (ALB), and other indicators. Immunologic remission was assessed by measurement of anti-phospholipase A2 receptor autoantibodies (PLA2R autoAbs).
Relative to baseline, the obinutuzumab group had significant decreases of PLA2R autoAbs (83.40 [55.90-344.36] vs 0.41 [0.17-1.20] RU/mL), 24-h UTP (8.90 [7.15-13.80) 1.82 [1.12-3.43] g/day), and B cells (312.61 [202.00-406.12) 0 [0-0] cells/μL), and a significant increase of serum ALB (25.90 [20.85-28.70] 42 [39.7-45.3] g/L) after six months. Nineteen of the evaluable patients (76% [55-91%]) achieved immunological remission at three months, 20 (80% [60-93%] achieved immunological remission at six months, and 16 (64% [42-83%] achieved partial response (PR) at three-months. After six-months, no patients achieved complete remission, but 19 (76% [55-91%]) achieved PR. Before the second dose of obinutuzumab, the CD19+ B cell count in 20 patients (80%) [60%-93%] was less than 1 cell/μL, and 18 patients had counts of 0 cells/μL. At the 6-month follow-up, the rituximab and obinutuzumab groups had no significant differences in immunological remission (80% vs 64%; OR: 2.29 [0.62-8.47]; P=0.211) or clinical remission (76% vs 59%; OR: 2.19 [0.63-7.66]; P=0.215]. No patients experienced serious adverse events.
This retrospective analysis suggests that obinutuzumab may have potential as an initial therapeutic option for patients with PMN, although larger controlled studies are needed for confirmation.
膜性肾病（MN）可导致肾病综合征。B细胞在MN发病中起作用，但现有治疗方法往往效果不佳。我们通过分析奥妥珠单抗对原发性MN（PMN）患者的疗效来填补这一治疗空白。
47例PMN患者随访6个月，其中25例接受奥妥珠单抗治疗，22例（对照组）接受利妥昔单抗治疗。通过24小时尿总蛋白（24-h UTP）、血清白蛋白（ALB）及其他指标评估治疗反应。通过检测抗磷脂酶A2受体自身抗体（PLA2R自身抗体）评估免疫缓解情况。
与基线相比，奥妥珠单抗组6个月后PLA2R自身抗体（83.40[55.90 - 344.36]对0.41[0.17 - 1.20]RU/mL）、24-h UTP（8.90[7.15 - 13.80]对1.82[1.12 - 3.43]g/天）和B细胞（312.61[202.00 - 406.12]对0[0 - 0]细胞/μL）显著降低，血清ALB显著升高（25.90[20.85 - 28.70]对42[39.7 - 45.3]g/L）。19例可评估患者（76%[55 - 91%]）在3个月时达到免疫缓解，20例（80%[60 - 93%]）在6个月时达到免疫缓解，16例（64%[42 - 83%]）在3个月时达到部分缓解（PR）。6个月后，无患者达到完全缓解，但19例（76%[55 - 91%]）达到PR。在第二次注射奥妥珠单抗前，20例患者（80%）[60% - 93%]的CD19+B细胞计数低于1细胞/μL，18例患者计数为0细胞/μL。在6个月随访时，利妥昔单抗组和奥妥珠单抗组在免疫缓解（80%对64%；OR：2.29[0.62 - 8.47]；P = 0.211）或临床缓解（76%对59%；OR：2.19[0.63 - 7.66]；P = 0.215）方面无显著差异。无患者发生严重不良事件。
这项回顾性分析表明，奥妥珠单抗可能有潜力作为PMN患者的初始治疗选择，尽管需要更大规模的对照研究来证实。
