Effect of abrocitinib on skin biomarkers in patients with moderate- to- severe atopic dermatitis – JADE MOA

This was the first study to characterize the mechanism of action of abrocitinib in patients with moderate-to-severe atopic dermatitis (AD). In this Phase 2a trial, 46 adults were randomized 1:1:1 to abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks.

The primary endpoint was change from baseline in key skin biomarkers associated with inflammation, epidermal hyperplasia, T-helper 2 (Th2) immune response, and Th22 immune response through Week 12. Secondary endpoints included changes in gene expression in skin lesions, Secondary endpoints included changes in gene expression in skin lesions, efficacy endpoints (Investigator's Global Assessment [IGA] 0/1, Eczema Area and Severity Index [EASI]-50/75/90, and Peak Pruritus Numerical Rating Scale [PP-NRS]-4). Safety assessments were also performed.

Compared with placebo, abrocitinib 200 mg significantly reduced biomarkers of inflammation, epidermal hyperplasia, and Th22 immune response from baseline in a dose-dependent manner at Week 12. Reductions from baseline were observed as early as Week 2 with abrocitinib 200 mg and by Week 4 with abrocitinib 100 mg. For Th2-associated biomarkers, CCL17 expression was significantly reduced from baseline at Week 12 with abrocitinib 200 mg, while CCL18 expression was significantly reduced from baseline at Weeks 2, 4, and 12 and was significantly lower versus placebo at Week 12. No significant differences were observed for CCL26. Reductions in molecular markers of epidermal hyperplasia correlated with improvements in itch, disease severity, and skin clearance.

Safety was consistent with the known abrocitinib profile: 54% of patients reported at least one treatment-emergent adverse event, most commonly nausea, dizziness, and headache were the most common TEAEs reported by patients treated with abrocitinib. There were no new or unexpected safety findings in either abrocitinib group.