Impact of Dupilumab Therapy on Skin Barrier Function in Patients With Moderate‐to‐Severe Atopic Dermatitis: A Phase IV, Non‐Randomized, Open‐Label, Parallel‐Group Clinical Study

Dupilumab improves skin barrier function in patients with atopic dermatitis (AD), but data for Chinese patients are limited. This 16‐week, prospective, exploratory study investigated the impact of dupilumab on skin barrier function in Chinese patients with moderate‐to‐severe AD. Forty‐four participants (24 patients with AD and 20 healthy volunteers) were enrolled. Patients with AD received dupilumab treatment every 2 weeks and were followed up to Week 16. Tape‐stripped stratum corneum samples were collected from participants at seven specific time points for proteomic and lipidomic profiling, together with transepidermal water loss (TEWL) measurement. At Week 16, TEWL after five tape strips was significantly reduced versus baseline (adjusted p = 0.0006). Proteomics revealed significant upregulation of sphingolipid and other lipid metabolism pathways within the first 2 weeks, coinciding with early TEWL improvement; keratinocyte differentiation and keratinization pathways were enriched from Week 8 through Week 16. Lipidomics revealed that specific dysregulated ceramides—CER(d16:0/16:0), CER(d16:0/20:3), CER(t20:1/23:0), and CER(t20:1/24:1)—showed significant changes by Weeks 2–8 and completely normalized by Week 16. Dupilumab improved skin barrier function in Chinese patients with moderate‐to‐severe AD, accompanied by dynamic molecular changes; these correlative findings require functional validation to establish causality. Trial Registration: ClinicalTrials.gov NCT05624112.