Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA.
Division of Rheumatology, VA Palo Alto Health Care System, Palo Alto, CA, USA.
Expert Opin Investig Drugs. 2020 Apr;29(4):349-362. doi: 10.1080/13543784.2020.1743973. Epub 2020 Mar 25.
: Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by excessive collagen deposition, vascular dysfunction, and fibrosis of cutaneous and visceral organs. Current therapeutic options are limited and provide only modest benefit.: This review summarizes investigational agents in recent Phase I and II clinical trials evaluated for the treatment of SSc with a focus on skin in patients with early diffuse disease and interstitial lung disease. We performed a search on Pubmed and https://clinicaltrials.gov with keywords systemic sclerosis, Phase I clinical trial, and Phase II clinical trial to identify relevant studies from 2015 to 2019.: Therapeutic interventions in SSc should be guided by the level of disease activity and the degree of organ involvement. While most novel agents have failed to meet the primary endpoints of reducing skin thickening as measured by the modified Rodnan skin score, some have shown promise in improving the Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis (CRISS), reducing lung function decline, or improving patient-reported outcomes. However, most of the current evidence is based on small or open-label clinical trials. Well-designed, large, randomized, Phase III clinical trials are necessary to define the roles of investigational agents in treating SSc.
系统性硬化症（SSc）是一种自身免疫性结缔组织疾病，其特征是胶原过度沉积、血管功能障碍和皮肤及内脏器官纤维化。目前的治疗选择有限，只能提供适度的疗效。
本综述总结了近年来评估用于治疗弥漫性早期疾病和间质性肺疾病患者皮肤 SSc 的 I 期和 II 期临床试验中的研究药物，重点关注皮肤。我们在 Pubmed 和 https://clinicaltrials.gov 上使用了系统性硬化症、I 期临床试验和 II 期临床试验等关键词进行搜索，以确定 2015 年至 2019 年的相关研究。
SSc 的治疗干预应根据疾病活动程度和器官受累程度来指导。虽然大多数新型药物未能达到改良 Rodnan 皮肤评分衡量的皮肤增厚减少的主要终点，但有些药物在改善早期弥漫性皮肤系统性硬化症临床试验综合反应指数（CRISS）、减缓肺功能下降或改善患者报告的结局方面显示出了一定的疗效。然而，目前的大部分证据都基于小型或开放标签临床试验。需要进行设计良好、大型、随机的 III 期临床试验，以确定研究药物在治疗 SSc 中的作用。
