Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis - 14/09/12
Abstract |
Background |
Janus-associated kinases (JAKs) are involved in signal transduction from a variety of cytokines implicated in the pathogenesis of psoriasis, including interleukin (IL)-12, IL-23, and interferon-γ. INCB018424, a small molecule inhibitor of JAK1 and JAK2, inhibits cytokine-induced JAK/signal transducers and activators of transcription signaling and the resultant production of inflammatory proteins (eg, IL-17).
Objective |
We sought to demonstrate proof of concept in patients with stable plaque psoriasis.
Methods |
Patients were dosed with vehicle, 0.5% or 1.0% INCB018424 phosphate cream once a day or 1.5% twice a day for 28 days. Additional groups included two active comparators (calcipotriene 0.005% cream or betamethasone dipropionate 0.05% cream).
Results |
Both the 1% and the 1.5% cream improved lesion thickness, erythema, and scaling and reduced lesion area compared with placebo. A composite lesion score decreased by greater than 50% with the efficacious doses of INCB018424 compared with 32% for vehicle controls. Topical application of INCB018424 was well tolerated with few mild adverse events noted. Mean plasma concentrations of INCB018424 after topical application of 0.5% to 1.5% cream were in the low nanomolar range, representing a fraction (<1%) of the half maximal inhibitory concentration (IC50) in whole blood for inhibition of cytokine-stimulated signal transducers and activators of transcription-3 phosphorylation.
Limitations |
This study was limited by the relatively short study duration and small sample size.
Conclusion |
Topical INCB018424 is safe, is well tolerated, and exhibits clinical activity in the topical treatment of psoriasis.
Le texte complet de cet article est disponible en PDF.Key words : INCB018424, Janus-associated kinase inhibitor, psoriasis
Abbreviations used : AE, BID, ECG, IFN, IL, JAK, QD, STAT
Plan
Supported by Incyte Corp. |
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Disclosure: Drs Punwani, Scherle, Shi, Liang, Yeleswaram, Levy, and Williams and Mr Flores are employees of Incyte Corp. Dr Gottlieb is a consultant for Incyte Corp. |
Vol 67 - N° 4
P. 658-664 - octobre 2012 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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