Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin.

BACKGROUND

Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited.

OBJECTIVE

In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects.

METHODS

Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Punch biopsy specimens were collected for biomarker analysis at baseline from all participants, then from AD patients only at day 8 (optional) and day 15.

RESULTS

Compared to the vehicle, crisaborole significantly reversed dysregulation of the overall lesional proteome and of key markers and pathways (eg, Th2, Th17/Th22, and T-cell activation) associated with AD pathogenesis toward both nonlesional and normal skin. Significant clinical correlations were observed with markers associated with nociception and Th2, Th17, and neutrophilic activation.

LIMITATIONS

Study limitations include predominance of white patients in the cohort, relatively short treatment time, and regimented administration of crisaborole.

CONCLUSION

Our results demonstrate crisaborole-induced normalization of the AD proteome toward a nonlesional molecular phenotype and further support topical PDE4 inhibition in the treatment of mild to moderate AD.

Informations de copyright

Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of interest Dr Bissonnette is an Advisory Board Member, Consultant, Speaker and/or Investigator for and received honoraria and/or grants from AbbVie, Almirall, Amgen, AnaptysBio, Arcutis, Bausch Health, Boehringer-Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly, Escalier, Janssen, Kyowa Kirin, LEO Pharma, Nimbus, Pfizer, Regeneron, Sienna, and UCB. He is also an employee and shareholder of Innovaderm Research. Dr Guttman-Yassky has served as a consultant for AbbVie, Amgen, Allergan, Asana Bioscience, Celgene, Concert, Dermira, DS Biopharma, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharmaceuticals, Lilly, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron, Sanofi, and Union Therapeutics; a member of advisory boards of Allergan, Asana Bioscience, Celgene, DBV, Dermavant, Dermira, Escalier, Galderma, Glenmark, Kyowa Kirin, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, and Sanofi; and a recipient of research grants from AbbVie, AnaptysBio, AntibioTx, Asana Bioscience, Boehringer-Ingelheim, Celgene, DBV, Dermavant, DS Biopharma, Galderma, Glenmark, Innovaderm, Janssen Biotech, Kiniska Pharma, LEO Pharmaceuticals, Lilly, Medimmune, Sienna Biopharmaceuticals, Novan, Novartis, Ralexar, Regeneron, Pfizer, UCB, and Union Therapeutics. Dr Pavel is an employee of the Icahn School of Medicine at Mount Sinai and conducts research sponsored by Pfizer. Dr Werth is a full-time employee of and shareholder in Pfizer, Inc. Kim, Duca, Cheng, Carroll, Facheris, Estrada, Cha, Nocka, and Zhang have no conflicts of interest to declare.