Targeted therapy for systemic sclerosis: how close are we?

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.

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

The authors wish to thank David Buss for his editorial 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.

Laboratory of Autoimmune Diseases Josep Font, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain

Department of Internal Medicine, Hospital Vall d'Hebron, Passeig Vall d'Hebron 119–129, 08035, Barcelona, Spain

Primary Care Research Group, IDIBAPS, University of Barcelona, CAP Les Corts, GESCLINIC, 08028, Barcelona, Spain

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