Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin
Journal of the American Academy of Dermatology, 2023
Kim M., Del Duca E., Cheng J., Carroll B., Facheris P., Estrada Y., Cha A., Werth J., Bissonnette R., Nocka K., Zang C., Pavel A., Guttman-Yassky E.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Dermatological Diseases | Pathophysiology | Skin Punch Biopsy Lysate |
Abstract
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.