Effectiveness and Safety of Upadacitinib in Patients with Moderate-to-Severe Atopic Dermatitis and Previous Failures of Th2 Biologics: A Propensity Score-Matched Study

Introduction: Real-world data comparing patients with atopic dermatitis (AD) initially treated with upadacitinib versus those previously treated with biologics or other JAK inhibitors are limited. Methods: We conducted a retrospective multicenter study of 524 patients with moderate-to-severe AD treated with upadacitinib to assess clinical outcomes over 52 weeks. A sub-analysis of 316 patients compared outcomes between those who had previously failed Th2 biologics (group A) and those who discontinued these treatments for reasons other than inefficacy or were bio-naïve (group B), using a Propensity Score matching method. Results: A significant clinical improvement starting from week 4 and continuing throughout the study period was observed in the overall population and both in group A and B. Group B showed greater improvements at later follow-up times, with a higher median EASI (Eczema Area and Severity Index) percentage improvement at week 52 (p=0.030), a significantly higher proportion of patients achieving EASI-90 and EASI-100 at week 36 (p=0.023, χ²=9.497). As for the P-NRS (Pruritus Numerical Rating Scale) and SD-NRS (Sleep Distrubances Numerical Rating Scale), group B had a significantly greater percentage of patients reporting a score of 0 or 1 at week 52 (P-NRS: p=0.017, χ²=5.665; SD-NRS: p=0.049, χ²=3.870). Group B also had a significantly higher percentage of patients reaching minimal disease activiy at week 52 (p=0.014, χ²=5.980). Conclusion: Upadacitinib proved to be effective in the long term not only as a first-line therapy but also in patients with a history of biologic treatment failure. However, patients in Group B consistently demonstrated better clinical responses at later follow-ups, suggesting that bio-naïve individuals and those who discontinued Th2 biologics for reasons other than inefficacy may respond more favorably to upadacitinib.