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

https://doi.org/10.1016/j.semarthrit.2012.06.001Get rights and content

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. Two additional 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.

Section snippets

Materials and Methods

We conducted a careful search for primary articles in MEDLINE/PubMed between January 2008 and February 2012 as well as for abstracts presented in 2008, 2009, 2010, and 2011 European League Against Rheumatism and American College of Rheumatology (ACR) conferences reporting on the therapeutic use of imatinib in SSc. Search terms included “imatinib” in combination with “systemic sclerosis”, “scleroderma”, “pulmonary hypertension”, “pulmonary fibrosis”, “interstitial lung disease”, “graft versus

Results

Our search retrieved a total of 100 primary articles. Among these there were 6 case reports and 1 case series describing the use of imatinib in SSc, comprising in all 13 patients, as well as 3 clinical studies, including 30, 20, and 10 subjects, respectively. In addition, 2 small clinical trials presented in the 2010 ACR conference and involving 27 and 9 SSc patients treated with imatinib, respectively, were also considered. A sixth pilot study of imatinib in SSc patients with lung involvement,

Discussion

The currently available data on the safety and efficacy of imatinib in the treatment of SSc come from case reports and 5 small, observational trials (39, 40, 41, 42), of which only 1 had a comparison arm (39). Despite the fact that positive experiences are published more frequently than negative experiences, a negative outcome was reported in 6 of 15 patients described in case reports and case series. Along this line, the first 2 studies by Spiera et al. (42) and Khanna et al. (40) and the

Acknowledgments

KE is supported by the European Commission research program INFLA-CARE (ECContract Number 223151).

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    The authors have no conflicts of interest to disclose.

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