Emerging drugs in phase 2/3 and selected phase 1/2 cellular-therapy trials: a glimpse into the future of systemic sclerosis treatment
Year: 2026
Type: review
Abstract: 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.
Source: Annals of the Rheumatic Diseases
Authors: Eisha Naveed, Alain Lescoat, Marco Matucci-Cerinic, Masataka Kuwana, Christopher P. Denton, Yannick Allanore, John D. Pauling, Francesco Del Galdo, Zsuzsanna McMahan, Jorg H.W. Distler, Janet Pope, Oliver Distler, Shervin Assassi, Robert Spiera, Lorinda Chung, Laura Cooney, Pei-Suen Tsou, John Varga, Dinesh Khanna
Institutions: University of Michigan, Inserm, École des Hautes Études en Santé Publique, Institut de Recherche en Santé, Environnement et Travail, Centre Hospitalier Universitaire de Rennes, Université de Rennes, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, University of Florence, Nippon Medical School, The Royal Free Hospital, University College London, Université Paris Cité, Hôpital Cochin, University of Bristol, University of Leeds, The University of Texas Health Science Center at Houston, Düsseldorf University Hospital, Fraunhofer Institute for Translational Medicine and Pharmacology, Heinrich Heine University Düsseldorf, St Joseph's Health Care, University of Zurich, University Hospital Zurich, Hospital for Special Surgery, Stanford Medicine, Stanford University, Michigan Medicine
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,870
OpenAlex ID: W7223331769