Funding sources This study was supported by the National ‘Programme Hospitalier de Recherche Clinique (PHRC) 2006’. We thank the ‘Association Française des Sclérodermiques (AFS)’, the ‘Groupe Français de Recherche sur la Sclérodermie (GFRS)’ and Novartis Pharmaceuticals for giving supplemental support to this study.
Imatinib mesylate in scleroderma-associated diffuse skin fibrosis: a phase II multicentre randomized double-blinded controlled trial
Article first published online: 5 OCT 2012
© 2012 The Authors. BJD © 2012 British Association of Dermatologists
British Journal of Dermatology
Volume 167, Issue 5, pages 1138–1144, November 2012
How to Cite
Prey, S., Ezzedine, K., Doussau, A., Grandoulier, A.-S., Barcat, D., Chatelus, E., Diot, E., Durant, C., Hachulla, E., de Korwin-Krokowski, J.-D., Kostrzewa, E., Quemeneur, T., Paul, C., Schaeverbeke, T., Seneschal, J., Solanilla, A., Sparsa, A., Bouchet, S., Lepreux, S., Mahon, F.-X., Chene, G. and Taïeb, A. (2012), Imatinib mesylate in scleroderma-associated diffuse skin fibrosis: a phase II multicentre randomized double-blinded controlled trial. British Journal of Dermatology, 167: 1138–1144. doi: 10.1111/j.1365-2133.2012.11186.x
Conflicts of interest None declared.
- Issue published online: 29 OCT 2012
- Article first published online: 5 OCT 2012
- Accepted for publication 17 June 2012
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.
Objectives 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.