特应性皮炎（AD）前沿文献精读特辑（J Am Acad Dermatol / Contact Dermatitis）

BACKGROUND: QY201 is a novel oral Janus kinase 1 and tyrosine kinase 2 inhibitor. OBJECTIVE: To evaluate the efficacy of multiple QY201 doses in moderate-to-severe atopic dermatitis (AD), and to inform dose selection for phase 3 studies. METHODS: In this phase 2, randomized, double-blind, placebo-controlled trial, 200 adults with moderate-to-severe AD were randomized 1:1:1:1 to receive QY201 (5 mg, 10 mg, or 20 mg twice daily [BID]) or placebo for 12 weeks. The primary endpoint was the proportion of patients achieving ≥75% improvement in Eczema Area and Severity Index (EASI-75) at week 12. RESULTS: EASI-75 response rates at week 12 were 72.9%, 84.7% and 81.4% in the 5 mg BID, 10 mg BID, and 20 mg BID groups, respectively, compared with 18.5% in the placebo group (all P<0.0001). Investigator's Global Assessment response rates were 44.7% (P=0.0011), 64.3% (P<0.0001), and 71.3% (P<0.0001), respectively, versus 12.4% with placebo. Treatment-emergent adverse events occurred in 74.0%, 75.5%, and 90.4% of patients receiving QY201, compared to 69.4% with placebo; most were mild or moderate. LIMITATIONS: Short follow-up and single-country population. CONCLUSION: The phase 2 findings support further evaluation of QY201 at doses of 10 mg BID and 20 mg BID in confirmatory phase 3 trials.

BACKGROUND/OBJECTIVES: Occupational hand dermatitis (HD) comprises irritant and allergic contact dermatitis (ICD and ACD), which share clinical features, often overlap, and may coexist with atopic dermatitis (AD), complicating diagnosis. The objective of this study is to explore whether stratum corneum (SC) biomarkers discriminate ICD from ACD. PATIENTS: We recruited 126 patients from the Occupational Dermato-allergology Clinics of the Amsterdam UMC. METHODS: SC samples were collected from lesional HD skin and patch test reactions to nickel, chromium, methylisothiazolinone, sodium lauryl sulfate (irritant), and control sites. Thirty-three biomarkers were analyzed. Random forest and penalized regression models were trained on the patch test dataset and validated in HD; an additional model was trained and validated in HD. Exploratory analyses evaluated discrimination among individual allergens and between AD, ICD and ACD. RESULTS: The patch test model showed good discrimination between ICD and ACD (mean AUC 0.85, 95% CI 0.82-0.87), driven primarily by skin barrier-related biomarkers. In HD, performance declined (mean AUC 0.51, 95% CI 0.26-0.76); sensitivity for ACD was 88%. Model trained and validated within HD achieved mean AUC of 0.60 (95% CI 0.57-0.64). Discrimination between individual allergens yielded mean AUC of 0.75 (95% CI 0.72-0.77). CONCLUSION: SC biomarkers discriminated ICD from ACD good in acute patch test, but showed limited discrimination in HD, reflecting differences between acute and chronic inflammation.