Improvement in skin inflammation and barrier function biomarkers with crisaborole treatment in atopic dermatitis (AD)

Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild-to-moderate AD. Its effects on AD skin biomarkers have not been evaluated. A phase 2a, single-center, vehicle-controlled, intrapatient study evaluated clinical efficacy and changes in skin biomarkers in 40 adults with mild-to-moderate AD. Two target lesions ≥3×3 cm with identical lesion Investigator’s Static Global Assessment of at least moderate were randomized 1:1 to double-blind crisaborole: vehicle, applied by the investigator twice daily for 14 days. Biopsy specimens were collected at days 1, 8 (optional), and 15 for microarray, qPCR, and immunohistochemistry analyses. Significant improvements were observed at first postbaseline assessment in pruritus (day 2; ie, 24h after first application), lesion signs (day 8), and transepidermal water loss (day 8) with crisaborole versus vehicle and were maintained to day 15. Crisaborole-treated lesions showed significant improvement in lesional transcriptional profile versus 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, including type 2 helper T-cell (Th2; Interleukin-13, CCL17, CCL22) and Th17/Th22 (S100A12, PI3) pathways and epidermal hyperplasia (keratin 16) (P<0.05 vs vehicle for all). Molecular profiles and epidermal pathology reversed toward nonlesional skin and significantly correlated with changes in lesion severity and barrier function. These findings demonstrate that crisaborole modulates key immune pathways and skin barrier function, with associated improvements in clinical efficacy, highlighting the therapeutic utility of targeting PDE4 in AD.