Emerging targets of disease-modifying therapy for systemic sclerosis

Elizabeth R. Volkmann; John Varga

doi:10.1038/s41584-019-0184-z

Emerging targets of disease-modifying therapy for systemic sclerosis

Elizabeth R. Volkmann, John Varga^*

^*Corresponding author for this work

Dermatology

Research output: Contribution to journal › Review article › peer-review

108 Scopus citations

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)
Pages (from-to)	208-224
Number of pages	17
Journal	Nature Reviews Rheumatology
Volume	15
Issue number	4
DOIs	https://doi.org/10.1038/s41584-019-0184-z
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41584-019-0184-z

Cite this

@article{964ff7f7a81241a1b5e1c798261129b3,

title = "Emerging targets of disease-modifying therapy for systemic sclerosis",

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.",

author = "Volkmann, {Elizabeth R.} and John Varga",

note = "Funding Information: 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. Funding Information: The authors thank D. Legares, S. Bhattacharyya and B. Korman for helpful discussions. The authors{\textquoteright} 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.). Publisher Copyright: {\textcopyright} 2019, Springer Nature Limited.",

year = "2019",

month = apr,

day = "1",

doi = "10.1038/s41584-019-0184-z",

language = "English (US)",

volume = "15",

pages = "208--224",

journal = "Nature Reviews Rheumatology",

issn = "1759-4790",

publisher = "Nature Research",

number = "4",

}

TY - JOUR

T1 - Emerging targets of disease-modifying therapy for systemic sclerosis

AU - Volkmann, Elizabeth R.

AU - Varga, John

N1 - Funding Information: 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. Funding Information: 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.). Publisher Copyright: © 2019, Springer Nature Limited.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85062018285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062018285&partnerID=8YFLogxK

U2 - 10.1038/s41584-019-0184-z

DO - 10.1038/s41584-019-0184-z

M3 - Review article

C2 - 30796362

AN - SCOPUS:85062018285

SN - 1759-4790

VL - 15

SP - 208

EP - 224

JO - Nature Reviews Rheumatology

JF - Nature Reviews Rheumatology

IS - 4

ER -

Emerging targets of disease-modifying therapy for systemic sclerosis

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this