Longitudinal Response Trajectories with Dupilumab or Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A Multicentre Real-World Study: IL-AD (Italian Landscape Atopic Dermatitis)

Introduction: Understanding how treatment responses evolve over time is essential for optimising therapeutic strategies in moderate-to-severe atopic dermatitis (AD). While clinical trials have demonstrated the efficacy of targeted therapies, real-world evidence describing longitudinal response trajectories remains limited. This study aimed to characterise temporal patterns of clinical response in patients with AD treated with dupilumab or upadacitinib in routine clinical practice. Methods: A multicentre real-world observational study was conducted using data from the Italian AD-Landscape platform, a structured clinical database collecting longitudinal information on patients receiving advanced systemic therapies for AD. Adult patients initiating dupilumab or upadacitinib between July 2019 and January 2026 were included if baseline and at least week-4 assessments were available. Disease severity and patient-reported outcomes were evaluated using the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Pruritus Numerical Rating Scale (P-NRS) and Sleep Numerical Rating Scale (S-NRS) at baseline and at weeks 4, 16, 36 and 52. Categorical response thresholds (EASI75, EASI90 and EASI100) and safety outcomes were analysed descriptively. Results: A total of 2625 patients were included (dupilumab n=2085; upadacitinib n=540). Both treatments produced rapid and sustained improvements in clinician-reported and patient-reported outcomes throughout the 52-week follow-up. Mean EASI scores decreased from 25.6 ± 6.5 to 2.2 ± 2.9 in the dupilumab group and from 19.1 ± 9.2 to 2.9 ± 5.7 in the upadacitinib group at week 52, respectively. Upadacitinib demonstrated faster early response kinetics, whereas dupilumab showed a progressive accumulation of clinical benefit over time, resulting in convergence of response rates during long-term follow-up. Safety findings were consistent with known mechanism-specific profiles. Conclusions: In this large real-world cohort, both dupilumab and upadacitinib provided substantial and sustained clinical improvements in moderate-to-severe AD. Distinct response kinetics were observed, with faster early responses with upadacitinib and progressively increasing responses with dupilumab, supporting a personalised approach to treatment selection in routine clinical practice.