Hu Xiaofan, Zhang Muyin, Xu Jing, Gao Chenni, Yu Xialian, Li Xiao, Ren Hong, Wang Weiming, Xie Jingyuan
Department of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China and Institute of Nephrology, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Clin J Am Soc Nephrol. 2024 Dec 1;19(12):1594-1602. doi: 10.2215/CJN.0000000000000555. Epub 2024 Aug 29.
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.
This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy (MN).
Patients with primary MN who had urine protein ≥3.5 g/24 hours and eGFR ≥30 ml/min per 1.73 m 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.
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; = 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; = 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/l versus 20 [3–58] cells/l, = 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], = 0.06) than rituximab. Both treatment regimens were well tolerated.
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.
在原发性膜性肾病患者中，奥妥珠单抗在12个月时诱导的缓解率高于利妥昔单抗。在原发性膜性肾病患者中，奥妥珠单抗与利妥昔单抗的安全性相似。
本研究比较了奥妥珠单抗和利妥昔单抗治疗原发性膜性肾病（MN）患者的有效性和安全性。
纳入原发性MN患者，尽管接受了6个月的血管紧张素转换酶抑制剂/血管紧张素II受体阻滞剂治疗，但尿蛋白≥3.5 g/24小时且eGFR≥30 ml/min per 1.73 m²，接受奥妥珠单抗或利妥昔单抗治疗，并根据年龄、性别、尿蛋白、eGFR和抗磷脂酶A2受体（PLA2R）抗体滴度通过倾向评分（比例：1:2）进行匹配。主要结局定义为12个月时部分或完全缓解的组合。使用逻辑回归模型、Kaplan–Meier曲线和绝对风险差异来比较奥妥珠单抗和利妥昔单抗的治疗有效性和安全性。
63例原发性MN患者纳入研究，21例接受奥妥珠单抗治疗，42例接受利妥昔单抗治疗。12个月时，奥妥珠单抗组21例患者中有20例达到主要结局，利妥昔单抗组42例患者中有28例达到主要结局（奥妥珠单抗与利妥昔单抗：95%对67%；优势比，10.00；95%置信区间，1.21至82.35；P = 0.03）。此外，奥妥珠单抗组患者获得更多完全缓解（奥妥珠单抗与利妥昔单抗：38%对14%；优势比，3.69；95%置信区间，1.08至12.68；P = 0.04）。在PLA2R相关的原发性MN亚组分析中，奥妥珠单抗组患者的CD19 B细胞计数持续较低（CD19 B细胞计数：中位数[四分位间距]0[0 - 6]个/μl对20[3 - 58]个/μl，P = 0.002），并且在6个月时比利妥昔单抗组更易实现免疫缓解（定义为PLA2R抗体<2 RU/ml）（奥妥珠单抗与利妥昔单抗：92%[13例中的12例]对64%[25例中的16例]，P = 0.06）。两种治疗方案耐受性均良好。
我们的研究表明，与利妥昔单抗相比，奥妥珠单抗在12个月时临床缓解的几率更高，这可能是由于在原发性MN患者中6个月时免疫缓解率更高且安全性相似。
