440 Topical phosphodiesterase 4 (PDE4) inhibitor crisaborole (crisa) improves skin transcriptomic and proteomic biomarkers of mild-to-moderate AD towards normal skin

This study was conducted to identify changes in genomic and proteomic skin profiles of 40 patients with AD lesions treated crisa, a nonsteroidal PDE4 inhibitor, vehicle compare them those nonlesional (NL) normal (N) skin. 2 randomly assigned (1:1 intrapatient manner) target were crisa or BID for 14 days. Punch biopsies collected from lesional 20 healthy controls at baseline days 8/15 treatment. Gene expression (microarray), OLINK (644 proteins), qRT-PCR analyses performed. Differentially expressed genes (DEGs) proteins (DEPs) determined by fold change >2 false discovery rate <0.05. Transcriptomic crisa-treated day 15 showed significant improvement towards NL N compared vehicle-treated (p<0.05), especially gene (478 DEGs; 92%NL/82%N) proteomics (315 DEPs; 59%NL/52%N) signatures Th1 (48%NL/44%N), Th2 (58%NL/51%N), Th17/Th22 (67%NL/38%N) pathways. These results corroborated PCR analysis showing both key AD-related biomarkers (innate immunity [IL6: 63%NL/52%N, IL8: 70%NL/59%N], [CXCL9: 39%NL/39%N], [IL31: 64%NL/51%N; CCL17: 48%NL/73%N; CCL22: 64%NL/68%N], Th17/22 [IL17A: 48%NL/44%N; IL19: 74%NL/66%N; PI3: 85%NL/62%N; IL23A: 76%NL/47%N] epidermal hyperplasia [KRT16: 68%NL/60%N; S100A9: 70%N/43%N]). Crisa treatment improves the transcriptomic immune/barrier such that they are comparable skin, highlighting therapeutic utility targeting patients.