背景：作为原发性膜性肾病（PMN）的初始治疗，仍有相当比例的患者利妥昔单抗未完全有效.这里,我们旨在评估obinutuzumab作为PMN患者初始治疗的有效性和安全性.
方法：在这个观察性案例系列中，纳入了被诊断为PMN并接受奥比努珠单抗作为初始治疗的患者.通过24小时尿总蛋白（24小时UTP）和血清白蛋白评估治疗反应，通过磷脂酶A2受体（PLA2R）抗体评估免疫缓解。
结果：纳入12例接受obinutuzumab作为初始治疗的PMN患者。超过6个月,观察到24hUTP水平显著降低(p=0.003),血清白蛋白水平升高(p<0.001).通过6个月的随访，两名患者(16.7%)达到完全缓解,8人(66.6%)达到部分缓解,和两个（16.7％）显示没有缓解。在3个月后观察到44.4%的可评估患者（n=9）的免疫缓解，在6个月时增加到100%(6/6)。除病例1、2和3外，其余患者的总B细胞计数在给予第二剂奥比努珠单抗之前降至5个细胞/μL以下，包括7名计数低至0细胞/μL的患者。58.3%(7/12)的患者报告了轻度至中度治疗相关不良事件(TRAEs)。没有严重的TRAE报告。
结论：Obinutuzumab作为PMN的初始治疗具有良好的潜力，具有良好的有效性和可管理的安全性。需要进一步的大规模前瞻性研究来证实这些发现。
BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN.
METHODS: In this observational
case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies.
RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/μL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/μL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported.
CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.
