Abrocitinib versus dupilumab: Impact on skin barrier function and proteomics in atopic dermatitis.

Abstract

The comparative impact of dupilumab and abrocitinib on skin barrier function and associated proteomics in atopic dermatitis (AD) remains not fully identified. To investigate the effects of dupilumab versus abrocitinib on skin barrier function and proteomic profiles in AD. In this study, 33 patients with moderate-to-severe AD were randomized into 2 groups: 16 received dupilumab and 17 received abrocitinib. Clinical outcomes and skin barrier parameters (transepidermal water loss and hydration) were assessed at baseline, 4 weeks, and 12 weeks. Skin tape strips were collected for four-dimensional data-independent acquisition-based proteomics. Both therapies improved skin barrier function, with abrocitinib achieving superior reductions in transepidermal water loss in nonlesional skin (P = .0168). Proteomic analysis revealed differentially expressed proteins predominantly associated with ceramide metabolism, neurobiology, and keratinocyte biology in AD. Key potential biomarkers were identified: arginase 1 and proteasome subunit beta type-6 in lesional skin, alongside grancalcin and phospholipase D3 in nonlesional skin. Abrocitinib enhanced the expression of crucial barrier proteins, such as filaggrin-2 and loricrin, in lesional skin-an effect not observed with dupilumab. The cohort size is small. While both abrocitinib and dupilumab effectively restore skin barrier function in AD, they exhibit distinct proteomic impacts.