Abstract
Systemic sclerosis (SSc) has the highest cause-specific mortality of all the connective tissue diseases, and the aetiology of this complex and heterogeneous condition remains an enigma. Current disease-modifying therapies for SSc predominantly target inflammatory and vascular pathways but have variable and unpredictable clinical efficacy, and none is curative. Moreover, many of these therapies possess undesirable safety profiles and have no appreciable effect on long-term mortality. This Review describes the most promising of the existing therapeutic targets for SSc and places them in the context of our evolving understanding of the pathophysiology of this disease. As well as taking an in-depth look at the immune, inflammatory, vascular and fibrotic pathways implicated in the pathogenesis of SSc, this Review discusses emerging treatment targets and therapeutic strategies. The article concludes with an overview of important unanswered questions in SSc research that might inform the design of future studies of treatments aimed at modifying the course of this disease.
Original language | English (US) |
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Pages (from-to) | 208-224 |
Number of pages | 17 |
Journal | Nature Reviews Rheumatology |
Volume | 15 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2019 |
Funding
E.R.V. declares that she has acted as a clinical trial investigator for Boehringer-Ingelheim and Genentech/Roche and is an advisory board member for Boehringer-Ingelheim. J.V. declares that he has acted as a clinical trial investigator for Corbus, Cytori, GlaxoSmithKline and Genentech/Roche; has received research grants from Bristol-Myers Squibb, Pfizer and the National Institutes of Health (NIH); and is an advisory board member for Boehringer-Ingelheim, Corbus, Emerald, Inventiva and Mitsubishi. The authors thank D. Legares, S. Bhattacharyya and B. Korman for helpful discussions. The authors’ research is supported by grants from the National Institutes of Health (AR42309 and R56AG054207 to J.V. and E.R.V.) and a grant from the Rheumatology Research Foundation (to E.R.V.).
ASJC Scopus subject areas
- Rheumatology