205 Tape strip genomic profiling of lesional and nonlesional atopic dermatitis skin identifies early and progressive normalization following treatment with abrocitinib

Atopic dermatitis (AD) is characterised by intense itch, immune activation, and barrier alterations. The phase 2a trial JADE MOA (NCT03915496) investigated the mechanism through which abrocitinib, a Janus kinase 1-selective inhibitor, improves moderate-to-severe AD. We evaluated the effect of abrocitinib on AD-associated biomarkers in lesional and nonlesional skin using tape strip-mediated sampling. Adults with moderate-to-severe AD were randomly assigned to receive abrocitinib (200 mg/100 mg) or placebo (12 weeks). Tape strips were collected from lesional and nonlesional skin at baseline, weeks 2 (lesional only), 4 and 12. Differentially-expressed genes (DEGs; fold change>1.5, false discovery rate<0.1) were identified using RNA sequencing. Correlations with disease severity (Eczema Area and Severity Index [EASI]; affected body surface area [BSA]; Investigator's Global Assessment [IGA]); itch (Numerical Rating Scale [NRS]) were identified using Spearman correlations. Tape strips were collected from 46 patients in JADE MOA and 32 untreated matched healthy controls. By week 12, abrocitinib induced dose-dependent normalization of the lesional AD versus the nonlesional baseline transcriptome (651 DEGs; 505 upregulated; 146 downregulated): 109% mean improvement with abrocitinib 200 mg, 64% with 100 mg, and 40% with placebo; improvements were also observed in nonlesional skin toward normal skin (200 mg, 31%; 100 mg, 20%). Abrocitinib resulted in dose-dependent downregulation of immune biomarkers (innate immunity: IL-6; Th1: IL-12B, CXCL9; Th2: IL-13/4R; Th17/22: S100A7/8, AHR), and upregulation of barrier genes (ELOVL3, CDH12/19) in lesional and nonlesional skin. Changes in EASI, BSA, and IGA scores correlated with changes in biomarkers related to T-cell activation and Th2/Th22-mediated inflammation (ICOS, CCL17/22, OX40, IL-7R, S100A7); NRS score correlated with itch-related, immune, and barrier biomarkers (TRPV2, RAMP1, FCER1a, OX40, IL-7R, S100A7/8/9, CCL17/22) in lesional and nonlesional skin (r>0.4; P<0.05 for all). These results suggest that tape strips accurately captured abrocitinib-induced molecular changes in lesional and nonlesional AD skin that correlated with disease severity.