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

BackgroundThis is the first report on the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the expression of skin biomarkers in patients with moderate-to-severe atopic dermatitis (AD).MethodsJADE MOA (NCT03915496) was a double-blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once-daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. The primary endpoint was change from baseline in markers of inflammation (matrix metalloproteinase [MMP]-12), epidermal hyperplasia (keratin-16 [KRT16]), T-helper 2 (Th2) immune response (C-C motif chemokine ligand [CCL]17, CCL18, and CCL26), and Th22 immune response (S100 calcium binding protein A8, A9, and A12 [S100A8, S100A9, and S100A12]) in skin through 12 weeks.ResultsA total of 46 patients received abrocitinib 200 mg (n = 14), abrocitinib 100 mg (n = 16), or placebo (n = 16). Abrocitinib improved AD clinical signs and reduced itch. Gene expression of MMP-12, KRT16, S100A8, S100A9, and S100A12 was significantly decreased from baseline with abrocitinib 200 mg (at Weeks 2, 4, and 12) and abrocitinib 100 mg (at Weeks 4 and 12) in a dose-dependent manner. Abrocitinib 200 mg resulted in significant decreases from baseline in CCL17 expression at Week 12 and CCL18 expression at Weeks 2, 4, and 12; no significant decreases were observed for CCL26.ConclusionsAlongside improvements in clinical signs and symptoms of AD, 12 weeks of abrocitinib treatment resulted in downregulation of genes associated with inflammation, epidermal hyperplasia, and Th2 and Th22 immune responses in the skin of patients with moderate-to-severe AD. AD is characterized by skin barrier and immune abnormalities. We assessed treatment response biomarkers of disease activity in the skin of patients with moderate-to-severe AD who received 12 weeks of treatment with abrocitinib, a JAK1-selective inhibitor, or placebo. Markers of inflammation, epidermal hyperplasia, and Th2- and Th22-related immune responses in skin lesions were significantly modulated with abrocitinib. AD, atopic dermatitis; CCL, chemokine C-C motif ligand; cDNA, complementary DNA; JAK1, Janus kinase 1; KRT16, keratin-16; MMP-12, matrix metalloproteinase 12; MOA, mechanism of action; qRT-PCR, quantitative real-time polymerase chain reaction; RNA, ribonucleic acid; S100A, S100 calcium-binding protein A; Th, T-helper cellaimage