Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis.
J Am Acad Dermatol
; 67(4): 658-64, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22281165
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 (IC(50)) 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Pirazóis
/
Janus Quinase 1
/
Janus Quinase 2
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article