Efficacy and Safety of Imatinib in Scleroderma

Summary

In vitro studies have shown that imatinib 1mM inhibits strongly the growth of cutaneous fibroblasts. The hypothesis is that imatinib inhibits PDGFR which is known to be a potential target for the molecule, as recently also proposed after the discovery of autoantibodies activating the PDGF receptors. Recent data indicate that TGFb is also a potential target of imatinib. Cutaneous scleroderma is characterized by progressive cutaneous fibrosis caused by hyperactive dermal fibroblasts. Since no established treatment for skin sclerosis in scleroderma is currently available. This study will test the safety and efficacy of imatinib in the treatment of patients with scleroderma and severe cutaneous involvement.

Timeline

Start

2007-12

Primary completion

2010-06

Completion

2010-12

Outcome

Missed primary endpoint

paper not statistically significantly different between the two groups (median +0·10 in imatinib group vs. -0·16 in placebo group, P = 0·098). PMID 23039171 ↗

paper failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis PMID 23039171 ↗

Publications

• Results Prey S, Ezzedine K, Doussau A, Grandoulier AS, Barcat D, Chatelus E, Diot E, Durant C, Hachulla E, de Korwin-Krokowski JD, Kostrzewa E, Quemeneur T, Paul C, Schaeverbeke T, Seneschal J, Solanilla A, Sparsa A, Bouchet S, Lepreux S, Mahon FX, Chene G, Taieb A. Imatinib mesylate in scleroderma-associated diffuse skin fibrosis: a phase II multicentre randomized double-blinded controlled trial. Br J Dermatol. 2012 Nov;167(5):1138-44. doi: 10.1111/j.1365-2133.2012.11186.x. Epub 2012 Oct 5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Imatinib	Small molecule	400 mg	Oral

Indications