生物制剂在原发性肾病综合征中的应用

doi:10.12372/jcp.2022.21e1440

摘要/Abstract

摘要：

原发性肾病综合征（INS）是儿童时期最常见的肾小球疾病,频复发、激素依赖、激素抵抗等难治性肾病综合征仍是目前临床INS治疗的难点,近年来国内外陆续有文献报道利妥昔单抗（RTX）及其他生物制剂应用于治疗难治性肾病综合征并取得良好的效果。文章就RTX及其他生物剂在INS的应用进展进行综述。

关键词: 肾病综合征, 生物制剂, 利妥昔单抗, 儿童

Abstract:

Idiopathic nephrotic syndrome (INS) is the commonest glomerular disease in children. Refractory nephrotic syndromes such as frequent relapses, steroid dependence and steroid resistance are still the current difficulties in clinical INS treatment. In recent years, it has been reported that rituximab (RTX) and other biological agents have been used in the treatment of refractory nephrotic syndrome and have achieved good results. This article reviews the application progress of RTX and other biological agents in INS.

Key words: nephrotic syndrome, biological agent, rituximab, child

王倩汇, 刘飞, 傅海东, 毛建华. 生物制剂在原发性肾病综合征中的应用[J]. 临床儿科杂志, 2022, 40(10): 787-794.

WANG Qianhui, LIU Fei, FU Haidong, MAO Jianhua. Application of biological agents in idiopathic nephrotic syndrome[J]. Journal of Clinical Pediatrics, 2022, 40(10): 787-794.

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生物制剂	主要作用机制	RCT文献（作者/年份）	例数	治疗效果
rituximab	靶向B细胞CD20,介导B细胞凋亡;通过CD80和CTLA4调节适应性免疫力并调节T细胞	Ravani / 2011 ^[12]	54	与标准治疗组相比,RTX治疗组蛋白尿、复发率及3个月无药概率更低
		Iijima / 2014 ^[13]	48	与安慰剂组相比,RTX组50％无复发期更长
		Basu / 2018 ^[15]	120	利妥昔单抗在维持疾病缓解和减少皮质类固醇暴露方面似乎比他克莫司更有效
		Ahn / 2018 ^[14]	61	治疗后6个月,RTX组缓解率较对照组更高,平均维持时间更长
		Ravani / 2021 ^[16]	30	RTX组复发风险更低,中位复发时间更长,对维持SDNS长期缓解有效
		Magnasco / 2012 ^[19]	31	利妥昔单抗组和安慰剂组之间蛋白尿程度无显著差异
ofatumumab	同rituximab	Ravani / 2020 ^[37]	13	1年后所有参与者均未出现蛋白尿完全或部分缓解,研究因无效而终止
ofatumumab	同rituximab	Ravani / 2021^[38]	140	在类固醇依赖性和钙调磷酸酶抑制剂依赖性肾病综合征患儿中,应用单剂量ofatumumab疗效并不优于单剂量RTX
abatacept	结合APC表面CD80,调节T细胞免疫	Trachtman / 2018^[49]	约90	结果未出
fresolimumab	结合TGF-β,抑制淋巴细胞分化及细胞因子产生	Vincenti / 2017 ^[52]	36	未达到减少蛋白尿的疗效终点,但与安慰剂相比,试验期间Fresolimumab组出现多次“部分缓解”的患者更多,肾功能相对更稳定
adalimumab	结合TNF-α,阻止炎症反应	Phase 1 trial / 2010^[53]	10	每10例蛋白尿患者中有4例降低50％以上
adalimumab	结合TNF-α,阻止炎症反应	Phase 2 trial / 2015^[54]	21	阿达木单抗治疗的7例受试者蛋白尿均未降低50％