Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial.

TitleImatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial.
Publication TypeJournal Article
Year of Publication2011
AuthorsSpiera RF, Gordon JK, Mersten JN, Magro CM, Mehta M, Wildman HF, Kloiber S, Kirou KA, Lyman S, Crow MK
JournalAnn Rheum Dis
Volume70
Issue6
Pagination1003-9
Date Published2011 Jun
ISSN1468-2060
KeywordsAdolescent, Adult, Aged, Benzamides, Biopsy, Dermatologic Agents, Female, Humans, Imatinib Mesylate, Male, Middle Aged, Piperazines, Protein Kinase Inhibitors, Pulmonary Diffusing Capacity, Pulmonary Fibrosis, Pyrimidines, Radiography, Scleroderma, Diffuse, Severity of Illness Index, Skin, Treatment Outcome, Ultrasonography, Vital Capacity, Young Adult
Abstract

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. ClinicalTrials.gov, NCT00555581.

DOI10.1136/ard.2010.143974
Alternate JournalAnn Rheum Dis
PubMed ID21398330
Grant ListUL1RR024996 / RR / NCRR NIH HHS / United States
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