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奥滨尤妥珠单抗治疗未经治疗的原发性膜性肾病:一项观察性病例系列研究。

Obinutuzumab in untreated primary membranous nephropathy: An observational case series.

机构信息

Department of Nephrology, Taiyuan Hospital of Peking University First Hospital, Taiyuan, Shanxi, China.

Department of Nutrition, Taiyuan Hospital of Peking University First Hospital, Taiyuan, Shanxi, China.

出版信息

Nephrology (Carlton). 2024 Nov;29(11):709-716. doi: 10.1111/nep.14331. Epub 2024 Jun 3.

Abstract

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.

摘要

背景

作为原发性膜性肾病(PMN)的初始治疗方法,仍有相当一部分患者对利妥昔单抗治疗不完全有效。在此,我们旨在评估奥滨尤妥珠单抗作为PMN 初始治疗的有效性和安全性。

方法

在这项观察性病例系列研究中,纳入了诊断为 PMN 且接受奥滨尤妥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

共纳入 12 例接受奥滨尤妥珠单抗作为初始治疗的 PMN 患者。在 6 个月内,24 小时 UTP 水平显著降低(p=0.003),血清白蛋白水平升高(p<0.001)。在 6 个月的随访中,2 例(16.7%)患者达到完全缓解,8 例(66.6%)患者达到部分缓解,2 例(16.7%)患者无缓解。在 3 个月时,9 例可评估患者中有 44.4%(4/9)患者出现免疫缓解,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 细胞计数在接受奥滨尤妥珠单抗第二剂之前均降至 5 个细胞/μL 以下,其中 7 例患者的计数低至 0 个细胞/μL。58.3%(7/12)的患者报告有轻微至中度的治疗相关不良事件(TRAEs)。无严重 TRAEs 报告。

结论

奥滨尤妥珠单抗作为 PMN 的初始治疗具有良好的疗效和可管理的安全性,具有很大的应用潜力。需要进一步的大规模前瞻性研究来证实这些发现。

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