AbstractBackgroundEvaluation of effectiveness and safety of new systemic treatments for atopic dermatitis (AD) after approval is important. There are few published data exceeding 52‐week therapy with dupilumab.ObjectivesTo examine the safety, effectiveness and drug survival of dupilumab in a Danish nationwide cohort with moderate‐to‐severe AD up to 104 weeks exposure.MethodsWe included 347 adult patients with AD who were treated with dupilumab and registered in the SCRATCH registry during 2017–2022.ResultsAt all visits, we observed improvement in AD severity measured by Eczema Area and Severity Index (EASI) [median (IQR)]. EASI score at baseline was 18.0 (10.6–25.2), at week 4: 6.5 (3.5–11.6), at week 16: 3.7 (1.2–6.2), at week 52: 2.0 (0.8–3.6), at week 104: 1.7 (0.8–3.8). While drug survival was high (week 52: 90%; week 104: 86%), AD in the head‐and‐neck area remained present in most patients at high levels; proportion with head‐and‐neck AD at baseline was 76% and 68% at week 104. 35% of patients reported any AE. Conjunctivitis was the most frequent (25% of all patients) and median time to first registration of conjunctivitis was 201 days.ConclusionsWhile 2‐year drug survival was 86%, dupilumab was unable to effectively treat AD in the head‐and‐neck area, and conjunctivitis was found in 25% of patients.