Imatinib in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and
internal organs and widespread vasculopathy. Patients with SSc are classified according to
the extent of cutaneous sclerosis: patients with limited SSc have skin thickening of the
face, neck, and distal extremities, while those with diffuse SSc have involvement of the
trunk, abdomen, and proximal extremities as well. The disease course varies depending on the
subtype of SSc. However, common features that result in significant morbidity and mortality,
in addition to cutaneous fibrosis, include Raynaud's phenomenon and digital ulcerations,
interstitial lung disease (ILD), and pulmonary arterial hypertension (PAH). Current
therapeutic options for patients with SSc and these clinical manifestations have shown
limited efficacy.

Imatinib antagonizes specific tyrosine kinases that mediate fibrotic pathways involved in the
pathogenesis of SSc, including c-Abl, a downstream mediator of transforming growth factor
(TGF)-beta, and platelet derived growth factor (PDGF) receptors. The efficacy of imatinib has
also been reported in the treatment of patients with refractory idiopathic PAH through its
effects on vascular remodeling. Based on the mechanism of action and preliminary patient
data, we hypothesize that imatinib may be effective in the treatment of the fibrotic and
vasculopathic features of patients with SSc. This is an open label pilot study to evaluate
the safety and efficacy of imatinib in patients with progressive SSc refractory to other
treatment(s). Validated measures of skin thickness and disease activity will be determined
over 6-months of therapy and compared with baseline measures.