Journal
CURRENT OPINION IN RHEUMATOLOGY
Volume 22, Issue 6, Pages 690-695Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/BOR.0b013e32833f1105
Keywords
scleroderma; systemic sclerosis; treatment; tyrosine kinase
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Funding
- Scleroderma Foundation
- New York Chapter of the Arthritis Foundation
- Weill-Cornell Clinical and Translational Science Center
- Rudolph Rupert Scleroderma Program
- Novartis Pharmaceuticals
- Bristol Myers Squibb
- United Therapeutics Corporation
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Purpose of review This article reviews the current evidence and rationale for the use of tyrosine kinase inhibitors as potential therapeutic interventions for systemic sclerosis. Recent findings The signaling cascades of the profibrotic cytokines transforming growth factor-beta and platelet-derived growth factor utilize tyrosine kinases. Preclinical studies have suggested potential efficacy of tyrosine kinase inhibitors in fibrosing disorders. Imatinib, dasatinib, and nilotinib treatment of scleroderma and normal fibroblasts leads to decreased production of extracellular matrix proteins in an in-vitro model. Several murine models demonstrate decreased skin thickening with tyrosine kinase inhibition. Case reports and one open-label trial suggest potential efficacy of imatinib in diffuse systemic sclerosis, although adverse events are common. One controlled and several uncontrolled trials are ongoing, and their results will better define the role of tyrosine kinase inhibition in the treatment of this disorder. Summary Tyrosine kinase inhibition as a potential strategy for the treatment of systemic sclerosis has been gaining more widespread interest based on preclinical data and open-label experiences. Large, multicenter, double-blind, randomized controlled trials are needed to assess the efficacy and safety of this approach in this complex disease.
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