Early Clinical Response Predicts Treatment Persistence in Advanced Therapy-naive Atopic Dermatitis.

Treatment persistence is a key real-world outcome integrating effectiveness and tolerability in moderate-to-severe atopic dermatitis (AD). We conducted a retrospective multicentre cohort study in 146 advanced therapy-naïve patients with moderate-to-severe AD initiating dupilumab, anti IL-13 agents or JAK inhibitors (JAKi) between April 2022 and April 2025 at 2 secondary-care hospitals in Madrid, Spain. Overall persistence rates were 82.9%, 69.8%, 59.5% and 54.5% at 6, 12, 18 and 24 months, respectively, with significant differences across therapeutic groups (log-rank p=0.025). In multivariable Cox regression, JAKi were associated with higher discontinuation risk compared with dupilumab (HR 1.79; 95% CI 1.05-3.05; p=0.034) and male sex was independently associated with increased discontinuation risk (HR 2.20; 95% CI 1.27-3.81; p=0.005). Early clinical response at week 16 was the strongest predictor: each 1% increase in EASI improvement was associated with a 3% reduction in discontinuation risk (HR 0.97; 95% CI 0.96 0.98; p<0.001). A parallel gradient was observed using patient-reported pruritus (NRS), confirming the predictive value of both objective and patient reported measures. Baseline biomarkers were not independently associated with persistence. These findings support week 16 as a clinically meaningful decision point for response-guided treatment evaluation in routine practice.