Targeted therapy for systemic sclerosis: how close are we?

ABSTRACT Despite recent etiopathogenetic advances, systemic sclerosis continues to be one of the most complex systemic autoimmune disease in terms of its therapeutic management. There is no

drug tested for any autoimmune disease that has not also been tested for systemic sclerosis, but none have proven effective. Substantial changes have occurred in the last decade, however,

with the appearance of new therapeutic targets and the consequent development of highly selective drugs, some of which, such as endothelin antagonists, are now widely used and others, such

as tyrosine kinase inhibitors, in which much hope has been placed. There is also increasing interest in evaluating drugs that are capable of blocking fibrotic processes mediated by

transforming growth factor β, which are currently used in nonautoimmune diseases (such as antidiabetic drugs or statins). Unfortunately, recent trials on these new molecules have produced

negative results. Increasing research into disease-specific therapies targeting distinct biological pathways should continue. In the future, it is hoped that the simultaneous or sequential

use of different drugs will provide better results than currently available monotherapies in patients with systemic sclerosis. KEY POINTS * Systemic sclerosis (SSc) is a systemic autoimmune

disease with a complex etiopathogenic scenario combining autoimmune, vascular and fibrotic damage * Oral endothelin antagonists are a highly specific outpatient treatment for the vascular

complications of SSc, which include pulmonary arterial hypertension, digital ulcers and complicated Raynaud phenomenon * Etiopathogenic advances have opened the door to the use of drugs

commonly used in other areas of medicine such as statins and antidiabetic agents * The development of selective therapies blocking fibrotic pathways is one of the principal novel and

promising therapeutic approaches in SSc * Studies suggest a change in approach from monotherapy to combined therapy, as the blockade of various pathways could produce better, longer-lasting

results * Improved prognostic classification and serological markers are needed to help quantify the contribution of each major etiopathogenic pathway in a given patient at a given time

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support SIMILAR CONTENT BEING VIEWED BY OTHERS SYSTEMIC LUPUS ERYTHEMATOSUS: UPDATED INSIGHTS ON THE PATHOGENESIS, DIAGNOSIS, PREVENTION AND THERAPEUTICS Article Open access 17 March 2025

TREAT-TO-TARGET IN SYSTEMIC LUPUS ERYTHEMATOSUS: ADVANCING TOWARDS ITS IMPLEMENTATION Article 17 January 2022 STATE-OF-THE-ART EVIDENCE IN THE TREATMENT OF SYSTEMIC SCLEROSIS Article 27

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assistance with this Review. Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and

answers of the MedscapeCME-accredited continuing medical education activity associated with this article. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Laboratory of Autoimmune Diseases

Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain Manuel Ramos-Casals & Pilar Brito-Zerón *

Department of Internal Medicine, Hospital Vall d'Hebron, Passeig Vall d'Hebron 119–129, 08035, Barcelona, Spain Vicent Fonollosa-Pla * Primary Care Research Group, IDIBAPS,

University of Barcelona, CAP Les Corts, GESCLINIC, 08028, Barcelona, Spain Antoni Sisó-Almirall Authors * Manuel Ramos-Casals View author publications You can also search for this author

inPubMed Google Scholar * Vicent Fonollosa-Pla View author publications You can also search for this author inPubMed Google Scholar * Pilar Brito-Zerón View author publications You can also

search for this author inPubMed Google Scholar * Antoni Sisó-Almirall View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence

to Manuel Ramos-Casals. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Ramos-Casals, M., Fonollosa-Pla, V., Brito-Zerón, P. _et al._ Targeted therapy for systemic sclerosis: how close are we?. _Nat Rev Rheumatol_ 6, 269–278 (2010).

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