Novel Pulmonary Imaging Biomarkers and Cutaneous Gene Expression Subsetting for Patient Selection and Outcome Assessment in the Dasatinib Treatment of Systemic Sclerosis-associated Interstitial Lung Disease

There are no effective treatments or clinical response markers for systemic sclerosis (SSc). We sought to assess the potential of novel imaging biomarkers and gene expression profiling approaches in a clinical trial of the tyrosine kinase inhibitor dasatinib in SSc patients with interstitial lung disease (SSc-ILD). Patients were enrolled in a single-arm open-label trial of dasatinib. Primary objective was to assess safety and pharmacokinetics. Secondary and exploratory outcomes included clinical assessments, quantitative high-resolution computed tomography (HRCT) of the chest, serum biomarkers, and intrinsic gene expression subset assignments in skin.

目前，系统性硬化症（systemic sclerosis, SSc）尚无有效的治疗方案或临床应答标志物。本研究旨在针对合并间质性肺病的系统性硬化症（systemic sclerosis-associated interstitial lung disease, SSc-ILD）患者开展的、采用酪氨酸激酶抑制剂（tyrosine kinase inhibitor）达沙替尼的临床试验中，评估新型影像学生物标志物与基因表达谱分析方法的应用潜力。本试验为单臂开放标签的达沙替尼临床试验，共纳入相关患者；其主要研究目的为评估安全性与药代动力学，次要及探索性结局指标则涵盖临床评估、胸部定量高分辨率计算机断层扫描（quantitative high-resolution computed tomography, HRCT）、血清生物标志物检测，以及皮肤组织的固有基因表达亚组分型。