722 Type 2 helper T-cell (Th2) effects of crisaborole versus 3 topical corticosteroids (TCSs) with a range of potencies: An ex vivo human skin model study

Abstract

The Th2 pathway plays a central role in the pathophysiology of atopic dermatitis (AD). Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. An ex vivo human skin model with Th2 cytokine and T-cell stimulation was used to compare the T-cell and Th2 cytokine activation effects of crisaborole with TCSs of varying potencies (hydrocortisone cream, 1% [lowest], hydrocortisone butyrate cream, 0.1% [lower-medium], and betamethasone valerate cream, 0.1% [medium]). Test articles were applied topically to human skin explants from 4 healthy (ie, non-AD) donors (5 replicates each) 16 hours prior to Th2 activation via a proprietary Th2 stimulation cocktail. To determine the effect of TCS application on the Th2-mediated inflammatory state of the tissue, 4 AD-associated biomarkers were chosen. RNA was isolated 24 hours after stimulation and quantitative-PCR was used to measure the gene expression of 4 biomarkers (interleukin [IL]-13, IL-31, interferon [INF]-γ, and matrix metallopeptidase 12 [MMP12]) in the explants. Topical application of crisaborole or any of the 3 TCSs resulted in a significant reduction (>50%) in activity for all 4 AD-associated biomarkers. There were no differences in biomarker expression between crisaborole and the 3 TCSs except for a numerically greater reduction in MMP12 for crisaborole compared with hydrocortisone cream, 1%.