Targeted therapies in systemic sclerosis: a narrative review of novel drugs in clinical trials

Purpose of review Systemic sclerosis (SSc) remains a therapeutic challenge, with conventional immunosuppressive strategies showing inconsistent effects and no disease modifying activity. The lack of head-head trials comparing immunosuppressives with emerging antifibrotic agents further complicates treatment decisions in SSc. This review aims to provide an update on the recent advances in targeted therapies for SSc, with a focus on novel biologics and small molecules that specifically modulate key mechanisms. Recent findings Advances in molecular profiling have revealed inflammatory and fibrotic endotypes within SSc while imaging studies support a fibroinflammatory subset, highlighting potential therapeutic targets. Summary A literature search for clinical trials between January 2020 and April 2025 from PubMed/MEDLINE, clinicaltrials.gov, euclinicaltrials.eu databases for targeted therapies in systemic sclerosis revealed a total of 117 clinical trials, of which we described the design, methods and endpoints from 14 studies (2 conference abstracts, 11 trials and 1 case series). These study results offer hope for patients with systemic sclerosis and pave way for future studies directing the development of patient-specific guidelines.