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特发性肺纤维化治疗药物临床试验进展
李怡华
叶俏
作者及单位信息
·
DOI： 10.3760/cma.j.issn.1001-0939.2020.03.025
randomized clinical trials of antifibrotic drug in idiopathic pulmonary fibrosis: an update
Li Yihua
Ye Qiao
Authors Info & Affiliations
Li Yihua
Ye Qiao
·
DOI： 10.3760/cma.j.issn.1001-0939.2020.03.025
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摘要

特发性肺纤维化（IPF）是一种慢性进行性纤维化性肺疾病，预后不良。目前抗肺纤维化药物吡非尼酮和尼达尼布已获批上市，能够部分地延缓IPF患者肺功能的下降。随着对肺纤维化机制的认识，针对不同部位、不同靶点的抗肺纤维化药物研发速度加快，呈现多元化的趋势。本文就IPF抗肺纤维化新药临床试验进展进行综述。

引用本文

李怡华,叶俏. 特发性肺纤维化治疗药物临床试验进展[J]. 中华结核和呼吸杂志,2020,43(03)：256-262.

DOI:10.3760/cma.j.issn.1001-0939.2020.03.025

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特发性肺纤维化（IPF）是一种慢性进行性肺纤维化疾病，表现为劳力性呼吸困难、肺功能下降，其胸部影像或病理特征是普通型间质性肺炎（UIP），疾病进展严重影响患者的生活质量，以致呼吸衰竭、死亡 [ 1 , 2 , 3 , 4 ]。IPF预后差，未经治疗的患者诊断后中位生存期为3~5年 [ 1 ]。以IPF为代表的慢性纤维化性肺疾病抗肺纤维化药物的研发，基于对肺纤维化机制的认识。目前已有吡非尼酮和尼达尼布被批准上市，其有效性和安全性已在随机对照试验（RCT）和真实世界研究中证实 [ 4 , 5 , 6 , 7 , 8 ]。针对不同部位、不同靶点的抗肺纤维化药物研发速度加快，呈现多元化的趋势（ 表1 ），本文主要阐述IPF治疗药物的临床试验进展。
药物 研发公司 作用靶点 作用部位 试验阶段 试验结果
吡非尼酮 Intermune 多靶点 FB 上市 延缓FVC下降
尼达尼布 Boehringer Ingel-hein PDGF/FGF/VEGF/TGF FB 上市 延缓FVC下降
Pamrevlumab（FG-3019） Fibrogen CTGF单克隆抗体 FB IIa期 延缓肺功能下降，减轻肺纤维化
PBI-4050 ProMetic BioScienc-es Inc 多靶点 FB Ⅱ期 延缓FVC占预计值%下降，安全性好
自毒素抑制剂（GLPG1690） Galapagos 抑制ATX，抑制LPA产生 FB IIa期 延缓FVC下降
LPA1受体抑制剂（BMS-986020） Bristol-Myers Squibb 抑制LPA1受体 FB Ⅱ期 延缓FVC下降
辛妥珠单抗（GS-6624） Gilead Sciences LOXL2单克隆抗体 FB Ⅱ期 阴性
CC-90001 Celgene JNK抑制剂 FB Ⅱ期 进行中
KD025 Kadmon Corpora-tion, LLC ROCK2抑制剂 FB Ⅱ期 进行中
重组人穿透素2（PROMO15） Promedior 抑制纤维细胞转化为成纤维细胞 AM Ⅱ期 延缓FVC、6MWTD下降
GSK2126458 GlaxoSmithKline 抑制mTOR，抑制CXCL12与CXCR4结合 AM Ⅰ期 抑制mTOR，降低肺纤维化区域葡萄糖信号异常
西罗莫司 Wyeth 抑制mTOR，抑制CXCL12与CXCR4结合 AM Ⅱ期 减轻肺纤维化
Lebrikizumab Roche IL-13单克隆抗体 AM Ⅱ期 阴性
利妥昔单抗 University of Ala-bama at Birming-ham CD20B细胞抗体 B细胞 Ⅱ期 研究中
STX-100（BG00011） Biogen Idec 整合素 Αvβ6单克隆抗体 AE-Ⅱ Ⅱ期 pSMAD2呈剂量依赖性减少，安全性待验证
Tipelukast MediciNova LTB4抑制剂 AE-Ⅱ Ⅱ期 进行中
抗肺纤维化新药临床试验一览表

注：FB为成纤维细胞；AM为肺泡巨噬细胞；AE-Ⅱ为Ⅱ型肺泡上皮细胞

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备注信息
A
叶俏，Email: mocdef.aabnisgnayoahc_oaiqey
B
所有作者均声明不存在利益冲突
C
国家自然科学基金 (81970061)
首都临床特色应用研究 (Z181100001718118)
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