处于2/3期及特定1/2期细胞疗法试验中的新兴药物：窥见系统性硬化症治疗的未来。
完整摘要 · 中文译文
系统性硬化症（SSc）是一种累及多器官的复杂自身免疫性疾病。SSc与风湿性疾病中最高的死亡率相关，并显著降低生活质量。因此，研究重点一直集中在理解其病因发病机制以及开发相关靶向治疗上。过去十年间，器官特异性治疗（如托珠单抗和尼达尼布用于肺纤维化）已被引入，用于管理SSc的各种表现。然而，目前缺乏针对整体疾病的获批疗法。当前，许多新化合物正在正在进行的临床试验中进一步评估。本文综述目前处于2期和3期试验中的药物，并重点介绍它们在SSc中靶向的关键疾病机制。近期在理解SSc发病机制方面的进展促进了可干预分子和细胞通路的识别，从而推动了对靶向治疗策略的检验。同时，越来越重视患者分层和个体化治疗方法，以优化临床试验设计、改善治疗反应性并提高试验结果的普遍适用性。在新兴治疗中，细胞治疗，包括嵌合抗原受体T细胞治疗，代表了一项重大创新。这种范式转变为改善系统性硬化症结局提供了巨大潜力。
完整摘要 · 英文原文
Systemic sclerosis (SSc) is a complex autoimmune disease that affects multiple organs. SSc is associated with the highest mortality rate among rheumatic diseases and significantly diminishes quality of life. Consequently, research efforts have focused on understanding its etiopathogenesis and on developing related targeted therapies. Over the past decade, organ-specific therapies (such as tocilizumab and nintedanib for lung fibrosis) have been introduced to manage various manifestations of SSc. However, there is a lack of approved therapies for the overall disease. Currently, many novel compounds are being further evaluated in ongoing clinical trials. This article reviews drugs currently in phase 2 and phase 3 trials and highlights the key disease mechanisms they target in SSc. Recent advances in understanding the pathogenesis of SSc have facilitated the identification of actionable molecular and cellular pathways, leading to the testing of targeted therapeutic strategies. Concurrently, increasing emphasis is being placed on patient stratification and personalised treatment approaches to optimise clinical trial design, improve treatment responsiveness, and enhance the generalisability of trial outcomes. Among emerging treatments, cellular therapies, including chimeric antigen receptor T-cell therapy, represent a significant innovation. This paradigm shift offers substantial potential for improving outcomes in systemic sclerosis.