Batani Veronica, Colic Jelena, Scaletti Cristina, Molteni Raffaella, De Luca Giacomo, Bandini Giulia, Dagna Lorenzo, Annunziato Francesco, Matucci-Cerinic Marco, Campochiaro Corrado
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milano, Italy.
Department: Rheumatology Department, Vita Salute San Raffaele University, Milan, Italy.
Expert Rev Clin Immunol. 2026 Mar 2:1-19. doi: 10.1080/1744666X.2026.2636654.
Systemic sclerosis (SSc) is increasingly understood as a triad of immune dysregulation, progressive fibrosis, and vasculopathy that evolve in parallel. The literature search was conducted using PubMed/MEDLINE, ClinicalTrials.gov, and the European Clinical Trials Database (EudraCT), including studies published in English up to October 2025.
This review summarizes the most recent therapeutic strategies now in clinical development and links each to its underpinning pre‑clinical and translational evidence, thereby mapping how mechanistic insights are reshaping drug pipeline in SSc.
A key breakthrough is the emergence of cell‑based immunotherapies, bispecific antibodies, and next‑generation small molecules that extend beyond adaptive immune targets to modulate innate immunity directly. Collectively, these agents illustrate a unifying concept: successful disease modification will require the synchronous interception of inflammation, fibrotic remodeling, and vascular injury rather than approaching these domains independently.
系统性硬化症（SSc）越来越被理解为一种由免疫失调、进行性纤维化和血管病变组成的三联征，它们并行发展。使用PubMed/MEDLINE、ClinicalTrials.gov和欧洲临床试验数据库（EudraCT）进行文献检索，包括截至2025年10月以英文发表的研究。
本综述总结了目前正在临床开发中的最新治疗策略，并将每种策略与其基础的临床前和转化证据联系起来，从而描绘出机制性见解如何重塑SSc的药物研发流程。
一个关键突破是基于细胞的免疫疗法、双特异性抗体和新一代小分子的出现，这些疗法不仅针对适应性免疫靶点，还直接调节固有免疫。总体而言，这些药物阐明了一个统一的概念：成功的疾病改善需要同步阻断炎症、纤维化重塑和血管损伤，而不是独立地处理这些方面。
