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优化利妥昔单抗方案与特发性膜性肾病推荐方案的比较:一项单中心回顾性队列研究。

Optimized rituximab regimen versus recommended regimen for idiopathic membranous nephropathy: A single-center retrospective cohort study.

机构信息

Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

出版信息

Int Immunopharmacol. 2024 Mar 30;130:111718. doi: 10.1016/j.intimp.2024.111718. Epub 2024 Feb 20.

Abstract

BACKGROUND

Rituximab (RTX) has become the first-line treatment for idiopathic membranous nephropathy (IMN). Compared with conventional therapy, rituximab therapy has a more favorable safety profile. However, the recommended RTX dose as a flux may have its limitations. The aim of this study was to investigate the clinical efficacy and safety of three regimens, including a cyclic corticosteroid-cyclophosphamide regimen and two different doses of RTX regimens, for the treatment of IMN.

METHODS

We recruited 58 patients with IMN confirmed by renal biopsy. 20 patients were treated with a cycle regimen, 22 patients were received RTX with 500 mg per week, totaling a dose of 2000 mg (optimized RTX group), and 16 patients received RTX with 1000 mg at day 1 and day 15 (recommended RTX group). Treatment responses, including complete remission (CR) and partial remission (PR), and outcome adverse events such as steroid diabetes, infections and a drop in white blood cell count, were compared among the three groups after 9 months of follow-up.

RESULTS

At 9-month follow-up, the composite remission rates (CR + PR) were 90 %, 72.7 %, and 75 % for the cycle regimen group, optimized RTX group, and recommended RTX group, respectively, with CR of 35 %, 22.7 %, and 25 %, respectively. There was no statistical difference between the three groups on CR and composite remission. Kaplan-Meier survival analyses showed no significant differences in cumulative CR rates and cumulative composite remission rates among the three groups (P = 0.632, P = 0.258). The cycle regimen group had a higher risk of steroid diabetes (35 %). Compared with the recommended RTX regimen, the optimized regimen reduced the incidence of adverse events of infection (9.1 % vs. 37.5 %, P = 0.049), especially in patients older than 60 years of age (P = 0.026). A lower anti-PLA2R at baseline may be associated with a higher risk of infection (P = 0.043).

CONCLUSIONS

The efficiency of low-dose and long-course of RTX regiment is not inferior to the recommended treatment regimen, and this regimen can effectively reduce the incidence of infection in patients with IMN. Moreover, we recommend a low-dose, long course of RTX treatment for the elderly.

摘要

背景

利妥昔单抗(RTX)已成为特发性膜性肾病(IMN)的一线治疗药物。与传统疗法相比,利妥昔单抗治疗具有更有利的安全性。然而,作为通量推荐的 RTX 剂量可能存在局限性。本研究旨在探讨三种方案(包括环磷酰胺-环孢菌素方案和两种不同剂量的 RTX 方案)治疗 IMN 的临床疗效和安全性。

方法

我们招募了 58 例经肾活检证实的 IMN 患者。20 例患者接受周期方案治疗,22 例患者接受每周 500mg 的 RTX 治疗,总剂量为 2000mg(优化 RTX 组),16 例患者接受第 1 天和第 15 天 1000mg 的 RTX(推荐 RTX 组)。在 9 个月的随访后,比较三组的治疗反应(完全缓解(CR)和部分缓解(PR))和不良事件结局,如类固醇糖尿病、感染和白细胞计数下降。

结果

在 9 个月的随访中,周期方案组、优化 RTX 组和推荐 RTX 组的复合缓解率(CR+PR)分别为 90%、72.7%和 75%,CR 分别为 35%、22.7%和 25%。三组之间在 CR 和复合缓解方面无统计学差异。Kaplan-Meier 生存分析显示三组累积 CR 率和累积复合缓解率无显著差异(P=0.632,P=0.258)。周期方案组类固醇糖尿病风险较高(35%)。与推荐 RTX 方案相比,优化方案降低了感染不良事件的发生率(9.1%比 37.5%,P=0.049),尤其是 60 岁以上的患者(P=0.026)。基线时抗-PLA2R 较低可能与感染风险增加相关(P=0.043)。

结论

低剂量、长疗程 RTX 方案的疗效不劣于推荐治疗方案,该方案可有效降低 IMN 患者感染的发生率。此外,我们建议对老年人采用低剂量、长疗程 RTX 治疗。

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