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J Allergy Clin Immunol. 2017 Oct;140(4):1032-1042.e13. doi: 10.1016/j.jaci.2017.01.027. Epub 2017 Feb 24.

Molecular signatures order the potency of topically applied anti-inflammatory drugs in patients with atopic dermatitis.

Author information

1
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
2
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
3
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY.
4
LEO Pharma A/S, Ballerup, Denmark.
5
Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Genetics and Genomics Science, Icahn School of Medicine at Mount Sinai, New York, NY; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY.
6
Innovaderm Research, Montreal, Quebec, Canada.

Abstract

BACKGROUND:

Atopic dermatitis (AD) presents a large unmet need for treatments with better safety and efficacy. To facilitate development of topical therapeutics, we need an efficient model for assessing different formulations and concentrations. The "plaque model" has been successfully implemented in patients with psoriasis, another common inflammatory disease, to assess the efficacy of topical treatments. This model has not been validated for AD, which has higher placebo responses and less stable lesions than psoriasis.

OBJECTIVE:

We aimed to assess changes in molecular signatures of intrapatient target lesions treated with topical therapeutics.

METHODS:

We enrolled 30 patients with mild-to-moderate AD in a randomized, double-blind, intraindividual comparison of 3 approved agents applied blindly at the investigator site daily for 14 days: pimecrolimus, betamethasone dipropionate, clobetasol propionate, and a vehicle/emollient control. Changes in total sign scores (TSSs), transepidermal water loss, and tissue biomarkers (determined by using RT-PCR and immunohistochemistry) were evaluated.

RESULTS:

TSSs showed improvements of 30%, 40%, 68%, and 76% at 2 weeks with vehicle, pimecrolimus, betamethasone, and clobetasol, respectively, with parallel changes in transepidermal water loss (P < .05). Significant differences versus vehicle values were limited to steroids (P < .0001). Steroids (particularly clobetasol) restored epidermal hyperplasia and terminal differentiation versus minimal changes with vehicle or pimecrolimus (P < .001). Levels of cellular infiltrates and cytokines (IL-13, IL-22, and S100As) were similarly reduced only by steroids (P < .001). TSS improvement correlated with changes in hyperplasia, infiltrates, and differentiation markers.

CONCLUSION:

We detected significant clinical and tissue differences between agents, providing a novel approach to study the differential effects of topical formulations using a limited sample size.

KEYWORDS:

Atopic dermatitis; biomarkers; emollients; plaque model; psoriasis; topical calcineurin inhibitor; topical steroids; topical treatments

PMID:
28238742
DOI:
10.1016/j.jaci.2017.01.027
[Indexed for MEDLINE]
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