BACKGROUND: There are no effective treatments or validated clinical response 
markers in systemic sclerosis (SSc). We assessed imaging biomarkers and 
performed gene expression profiling in a single-arm open-label clinical trial of 
tyrosine kinase inhibitor dasatinib in patients with SSc-associated interstitial 
lung disease (SSc-ILD).
METHODS: Primary objectives were safety and pharmacokinetics. Secondary outcomes 
included clinical assessments, quantitative high-resolution computed tomography 
(HRCT) of the chest, serum biomarker assays and skin biopsy-based gene 
expression subset assignments. Clinical response was defined as decrease of >5 
or >20% from baseline in the modified Rodnan Skin Score (MRSS). Pulmonary 
function was assessed at baseline and day 169.
RESULTS: Dasatinib was well-tolerated in 31 patients receiving drug for a median 
of nine months. No significant changes in clinical assessments or serum 
biomarkers were seen at six months. By quantitative HRCT, 65% of patients showed 
no progression of lung fibrosis, and 39% showed no progression of total ILD. 
Among 12 subjects with available baseline and post-treatment skin biopsies, 
three were improvers and nine were non-improvers. Improvers mapped to the 
fibroproliferative or normal-like subsets, while seven out of nine non-improvers 
were in the inflammatory subset (p = 0.0455). Improvers showed stability in 
forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), 
while both measures showed a decline in non-improvers (p = 0.1289 and p = 
0.0195, respectively). Inflammatory gene expression subset was associated with 
higher baseline HRCT score (p = 0.0556). Non-improvers showed significant 
increase in lung fibrosis (p = 0.0313).
CONCLUSIONS: In patients with SSc-ILD dasatinib treatment was associated with 
acceptable safety profile but no significant clinical efficacy. Patients in the 
inflammatory gene expression subset showed increase in skin fibrosis, decreasing 
pulmonary function and worsening lung fibrosis during the study. These findings 
suggest that target tissue-specific gene expression analyses can help match 
patients and therapeutic interventions in heterogeneous diseases such as SSc, 
and quantitative HRCT is useful for assessing clinical outcomes.
TRIAL REGISTRATION: Clinicaltrials.gov NCT00764309.