Objective To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc).
Methods In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment.
Results Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=−4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology.
Conclusions Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted.
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Funding This study was supported by the Rudolph Rupert Scleroderma Program at the Hospital for Special Surgery and by Novartis Pharmaceuticals who provided drug as well as partial financial support. JKG was supported by an Arthritis Foundation New York Chapter Fellowship and by grant UL1RR024996 of the Clinical and Translational Science Center at Weill–Cornell Medical Center.
Competing interests None.
Ethics approval This study was conducted with the approval of the Hospital for Special Surgery and Weill–Cornell Medical Center.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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