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Systemic sclerosis (SSc) is a fibrosing connective tissue disease with significantly increased mortality. Therapeutic options to treat fibrosis are limited. The small molecule tyrosine kinase inhibitor imatinib and related drugs such as dasatinib and nilotinib target simultaneously two of the major profibrotic pathways, TGFbeta- and PDGF- signaling. Imatinib, dasatinib and nilotinib inhibit collagen synthesis in cultured fibroblasts and have potent anti-fibrotic effects in animal models of different fibrotic diseases. Moreover, several case reports, case series and uncontrolled studies on patients with SSc, mixed connective tissue disease, nephrogenic systemic fibrosis and in particular sclerodermatous graft versus host disease (cGvHD) report regression of fibrosis and good tolerability. However, the results of larger controlled trials, which are currently ongoing, are needed before any conclusions on efficacy and tolerability can be drawn. Until the results of these trials are available, we discourage off-label use of Imatinib in single patients.

Tyrosine kinase inhibitors for the treatment of fibrotic diseases such as systemic sclerosis: towards molecular targeted therapies