Dupilumab versus upadacitinib in atopic dermatitis: comparative effectiveness, response kinetics, and treatment persistence

BACKGROUND: Comparative real-world evidence on dupilumab versus upadacitinib for atopic dermatitis (AD), applying methods that address confounding by treatment selection, remains limited. We compared EASI-75 at week 16, response kinetics, treatment persistence, and safety. RESEARCH DESIGN AND METHODS: This retrospective, two-center, active-comparator cohort included adults with moderate-to-severe AD initiating dupilumab or upadacitinib under a national reimbursement framework during 2025-2026. EASI-75 at week 16 (non-responder imputed) was the primary outcome. Treatments were compared using propensity-score overlap weighting. RESULTS: Of 100 initiators (52 dupilumab, 48 upadacitinib), 72 had sufficient potential follow-up for week 16, and 36 achieved EASI-75 (60.0% upadacitinib vs 40.5% dupilumab). After adjustment, the between-class estimate was imprecise (adjusted risk difference 12.4% points, 95% CI - 22.0 to 43.7; adjusted risk ratio 1.24, 95% CI 0.66-2.54), and the association was attenuated among advanced-therapy-naive patients. Week-52 treatment persistence was numerically higher with dupilumab (82.9% vs 64.5%; adjusted hazard ratio for discontinuation 3.09, 95% CI 0.89-10.71). CONCLUSIONS: The unadjusted efficacy advantage for upadacitinib was attenuated after accounting for confounding by treatment selection. Exploratory differences in response kinetics and treatment persistence require confirmation in larger cohorts with more complete follow-up.