The following is a summary of “Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin,” published in the AUGUST 2023 issue of Dermatology by Kim, et al.
Long-term safe and effective topical treatments for atopic dermatitis (AD) are limited. For a phase 2a study, researchers sought to investigate the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, through proteomic analysis in adults with mild to moderate AD and healthy subjects.
The single-center study included 40 adults with mild to moderate AD and 20 healthy subjects. Within the AD cohort, two target lesions were randomized in an intrapatient (1:1) manner to receive double-blind crisaborole/vehicle applied twice daily for 14 days. Biomarker analysis was performed on punch biopsy specimens collected at baseline from all participants and from AD patients only on days 8 (optional) and 15.
Crisaborole effectively restored the dysregulation of the whole lesional proteome and important indicators and pathways linked to AD pathogenesis, including Th2, Th17/Th22, and T-cell activation. The treatment normalized the AD proteome towards a nonlesional molecular profile similar to that of nonlesional and healthy skin. Markers linked to nociception, Th2, Th17, and neutrophilic activation were found to have significant clinical associations.
The study’s results demonstrated that crisaborole induces normalization of the AD proteome towards a nonlesional molecular phenotype, supporting the use of topical PDE4 inhibition in the treatment of mild to moderate AD.