系统性硬皮病靶向治疗研究进展  

Advances in targeted therapies for systemic sclerosis

作　　者：肖嵘[1] 刘佳倪 XIAO Rong;LIU Jiani(Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]中南大学湘雅二医院,湖南长沙410011

出　　处：《皮肤性病诊疗学杂志》2024年第5期287-296,共10页Journal of Diagnosis and Therapy on Dermato-venereology

基　　金：国家自然科学基金面上项目(82373486,82073449);国家自然科学基金青年项目(82304024,82001738,82003363,82203932,82203930);湖南省研究生科研创新项目(CX20220343)。

摘　　要：系统性硬皮病(SSc)作为一种免疫介导的慢性结缔组织疾病,以皮肤、肺等多器官纤维化为主要临床表现,属于罕见病范畴,但发病率和死亡率在风湿免疫性疾病中均排在前列。目前尚无有效的治疗药物。近年来研究发现,T/B淋巴细胞、成纤维细胞、内皮细胞等相互作用及各种促炎促纤维化信号分子激活在其发生发展中起着关键性作用,在此基础上正在研发系列靶向药物。其中靶向B细胞耗竭的CD20单克隆抗体(利妥昔单抗)、IL-6受体拮抗剂(托珠单抗)、多靶点酪氨酸激酶抑制剂(尼达尼布)等在国际上已被批准用于SSc或系统性硬化病相关间质肺疾病(SSc-ILD)治疗;其他靶向药物如Janus激酶抑制剂、多种白介素抑制剂等在临床试验阶段,部分展现初步应用前景。本文从靶向B淋巴细胞、T淋巴细胞、血管内皮细胞及促炎促纤维化信号分子4个方面综合最新证据,就靶向疗法在SSc中的研究进展进行综述。Systemic sclerosis(SSc),as an immune-mediated chronic connective tissue disease,is mainly characterized by fibrosis of multiple organs,including the skin and lungs.It is a rare disease,with a high incidence and mortality among rheumatic immune diseases.At present,there is no effective drug for the treatment of SSC.In recent years,it has been found that the interactions between T/B lymphocytes,fibroblasts,endothelial cells,and various pro-inflammatory and fibrotic signaling molecules play a crucial role in the occurrence and development of SSc.On this basis,a series of targeted drugs are currently being tested.CD20 monoclonal antibodies(Rituximab),IL-6 receptor antagonists(Tocilizumab),and multi-target tyrosine kinase inhibitors(Nintedanib)have been approved for the treatment of SSc or SSc-ILD by FDA.In addition,other targeted drugs such as Janus kinase inhibitors and various interleukin inhibitors have shown preliminary therapeutic potentials through clinical trials.This article reviews the research progress in targeted therapies for SSc by synthesizing the latest evidence from four aspects:targeting B lymphocytes,T lymphocytes,vascular endothelial cells,and pro-inflammatory and fibrotic signaling molecules.

关 键 词：系统性硬皮病 靶向治疗 生物制剂 小分子化合物 

分 类 号：R73[医药卫生—肿瘤]