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J Allergy Clin Immunol. 2019 Aug 13. pii: S0091-6749(19)31036-X. doi: 10.1016/j.jaci.2019.06.047. [Epub ahead of print]

Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial.

Author information

1
Innovaderm Research, Montreal, Quebec, Canada.
2
Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
3
Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; Ponce Health Sciences University School of Medicine, Ponce, Puerto Rico.
4
Pfizer, Collegeville, Pa.
5
Pfizer, Surrey, United Kingdom.
6
Pfizer, Groton, Conn.
7
Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.

Abstract

BACKGROUND:

Crisaborole ointment 2% is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). The mechanism of action of crisaborole and its effects on lesional measures of disease severity are not yet well defined.

OBJECTIVE:

This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the mechanism of action of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (n = 40) with mild-to-moderate AD.

METHODS:

Two target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Patients then applied crisaborole (open-label) to all affected areas for 28 days. Punch biopsy specimens were collected for biomarker analysis at baseline, day 8 (optional), and day 15.

RESULTS:

Crisaborole treatment resulted in early improvement in lesional signs/symptoms versus vehicle, with improvement in pruritus (pruritus numeric rating scale) observed as early as 24 hours after the first application. Crisaborole-treated lesions showed significant percentage improvement from baseline in lesional transcriptomic profile compared with vehicle at day 8 (91.15% vs 36.02%, P < 10-15) that was sustained until day 15 (92.90% vs 49.59%, P < 10-15). Crisaborole significantly modulated key AD biomarkers versus vehicle, including TH2 and TH17/TH22 pathways and epidermal hyperplasia/proliferation. Molecular profiles and epidermal pathology normalized toward nonlesional skin and correlated with clinical changes in lesion severity and barrier function.

CONCLUSION:

Crisaborole reversed biomarker profiles of skin inflammation and barrier function, with associated improvements in clinical efficacy measures, highlighting the therapeutic utility of targeting phosphodiesterase 4 in patients with AD.

KEYWORDS:

Atopic dermatitis; biomarker; crisaborole; gene expression; inflammation; phosphodiesterase 4; pruritus; transcriptome; transepidermal water loss

PMID:
31419544
DOI:
10.1016/j.jaci.2019.06.047
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