Therapeutic Inhibition of Tyrosine Kinases in Systemic Sclerosis: A Review of Published Experience on the First 108 Patients Treated with Imatinib

摘要

Objective: Experimental and clinical evidence suggest a therapeutic role for the tyrosine kinase inhibitor imatinib in fibrosing conditions. We evaluated published data on the safety and efficacy of imatinib for patients with systemic sclerosis (SSc), a severe autoimmune disease with significant morbidity and mortality. Methods: A careful search for all original articles and abstracts on the use of imatinib in SSc published in English from 2008 through February 2012 was performed.Twoadditional patients from our center are also described. Results: Five small observational clinical trials on the use of imatinib in severe SSc have been conducted and case reports and small series of refractory to current approaches patients have been reported, adding to a total of 108 patients having received this drug to date. In most of these patients imatinib was given for skin or pulmonary fibrosis. Encouraging results were reported in 3 of 4 studies, whereas the fifth study was prematurely terminated for safety reasons. Overall, clinical results are highly variable, ranging from ineffective or toxic responses to extremely encouraging clinical improvements in some severely ill patients. These discrepancies could partly reflect imatinib-related safety issues, in particular, SSc patients or idiosyncratic resistance to imatinib, as happens in chronic myelogenous leukemia and gastrointestinal stromal tumors, the drug's approved indications. Conclusions: The limited available experience suggests that imatinib could be considered as an individualized treatment approach in severe SSc and underscores the need to identify markers for selecting particular patients, who will safely respond to therapeutic inhibition of tyrosine kinases. ? 2013 Elsevier Inc.