title: Imatinib mesylate in scleroderma-associated diffuse skin fibrosis: a phase II multicentre randomized double-blinded controlled trial.
abstract: BACKGROUND
  Imatinib mesylate is a potent inhibitor of platelet-derived growth factor and transforming growth factor-β signalling pathways which may play a role in systemic sclerosis (SSc)-associated skin changes.
  
  
  OBJECTIVE
  We aimed primarily at assessing the efficacy of imatinib mesylate in scleroderma skin fibrosis.
  
  
  METHODS
  We performed a phase II double-blinded trial on patients with scleroderma with either morphoea involving > 20% of body surface area or SSc with extensive skin involvement: modified Rodnan Skin Score (mRSS) ≥ 20/51. Each patient was randomized to receive either imatinib mesylate 400 mg or placebo daily for a total of 6 months, and then was followed up 6 months after therapy discontinuation. Skin fibrosis was assessed by mRSS and measurement of the dermal thickness using skin biopsies performed at inclusion and at 6 months of treatment. In addition, quality of life (Dermatology Life Quality Index and modified Health Assessment Questionnaire for Scleroderma) was recorded at each visit, and pulmonary function before and after intervention.
  
  
  RESULTS
  Twenty-eight patients were included in the study with a mean age of 48·9 years (range 30-71): 25 had a diagnosis of a SSc and three of diffuse cutaneous scleroderma. Demographic data, frequency of organ involvement of SSc and mRSS were comparable between groups. At 6 months, the proportion of variation of mRSS from inclusion was not statistically significantly different between the two groups (median +0·10 in imatinib group vs. -0·16 in placebo group, P = 0·098). Similarly, changes in dermal thickness, quality of life and diffusion capacity for carbon monoxide were not significantly different between groups.
  
  
  CONCLUSIONS
  This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements.
authors.affiliation: Department of Dermatology, Hôpital Saint André, CHU de Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux, France. sorilla.prey@chu-bordeaux.fr
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authors.lastname: Solanilla
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authors.lastname: Bouchet
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authors.lastname: Lepreux
authors.forename: F-X
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mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011788:Quality of Life; D045743:Scleroderma, Diffuse / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016212:Transforming Growth Factor beta; D000068877:Imatinib Mesylate