Abstract
Systemic sclerosis (SSc) is a progressive fibrotic disorder with no legitimate effective treatment. Several clinical trials had investigated imatinib mesylate with a target dose of 400∼600 mg/day on SSc, and the efficacy is controversial with a generally poor tolerability. We herein reported six female Chinese patients with SSc administered with low-dose imatinib (200 mg/day) for a median of 23 months (10∼30 months). Patients displayed a decreased modified Rodman skin scores (mRSS) by a mean of 6.29 points after 6 months of treatment. Three patients who completed 2 years of treatment achieved a reduction of mRSS by 8, 18, and 30.5 points, respectively. Pulmonary function was improved or stabilized in two patients with interstitial lung disease. Severe gastrointestinal involvement in one patient was attenuated in terms of discontinuation of total parenteral nutrition and restoration of the serum albumin level. Imatinib was well-tolerated in general, although there were two severe adverse events: a bone fracture and a cerebral hemorrhage in two individuals. Both the adverse events were probably not directly related to imatinib and were recovered uneventfully. Our limited data, along with the review of the literature, suggested that low-dose imatinib might be effective and better tolerated in severe SSc that deserves further study.
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References
Gabrielli A, Avvedimento EV, Krieg T (2009) Scleroderma. N Engl J Med 360(19):1989–2003
Baroni SS et al (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 354(25):2667–2676
Ludwicka A et al (1995) Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma. J Rheumatol 22(10):1876–1883
Li Z, Jimenez SA (2011) Protein kinase Cdelta and c-Abl kinase are required for transforming growth factor beta induction of endothelial-mesenchymal transition in vitro. Arthritis Rheum 63(8):2473–2483
Sfikakis PP et al (2008) Imatinib for the treatment of refractory, diffuse systemic sclerosis. Rheumatology (Oxford) 47(5):735–737
van Daele PL et al (2008) Is imatinib mesylate a promising drug in systemic sclerosis? Arthritis Rheum 58(8):2549–2552
Chung L et al (2009) Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum 60(2):584–591
Tamaki Z et al (2011) Efficacy of low-dose imatinib mesylate for cutaneous involvement in systemic sclerosis: a preliminary report of three cases. Mod Rheumatol 22(1):94–99
Spiera RF et al (2011) Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis 70(6):1003–1009
Pope J et al (2011) Imatinib in active diffuse cutaneous systemic sclerosis: results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center. Arthritis Rheum 63(11):3547–3551
Khanna D et al (2011) A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosis-associated active interstitial lung disease. Arthritis Rheum 63(11):3540–3546
Distler O, Distler JHW, Varga J, et al. (2010) A multi-center, open-label, proof of concept study of imatinib mesylate demonstrates no benefit for the treatment of fibrosis in patients with early, diffuse systemic sclerosis [abstract]. Presented at the American College of Rheumatology Annual Scientific Meeting. Atlanta, GA
Anonymous (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 23(5):581–590
Clements P et al (1995) Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 22(7):1281–1285
Baccarani M et al (2009) Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 27(35):6041–6051
Druker BJ (2003) Imatinib mesylate in the treatment of chronic myeloid leukaemia. Expert Opin Pharmacother 4(6):963–971
Soria A et al (2008) The effect of imatinib (Glivec) on scleroderma and normal dermal fibroblasts: a preclinical study. Dermatology 216(2):109–117
Olivieri A et al (2009) Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Blood 114(3):709–718
Chung L, Ruiz P, Wood T, et al. (2010) Evaluation of an imatinib response gene signature in patients with systemic sclerosis [abstract]. Presented at the American College of Rheumatology Annual Scientific Meeting. Atlanta, GA
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Guo, L., Chen, Xx., Gu, Yy. et al. Low-dose imatinib in the treatment of severe systemic sclerosis: a case series of six Chinese patients and literature review. Clin Rheumatol 31, 1395–1400 (2012). https://doi.org/10.1007/s10067-012-2032-2
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DOI: https://doi.org/10.1007/s10067-012-2032-2