Effectiveness and safety of upadacitinib in patients with moderate-to-severe atopic dermatitis and prior inefficacy of T helper 2 biologics: a propensity score-matched study

Background Real-world data comparing patients with atopic dermatitis (AD) initially treated with upadacitinib vs. those previously treated with biologics or other Janus kinase inhibitors are limited. Objectives To assess clinical outcomes over 52 weeks of treatment with upadacitinib and to compare patients treated with upadacitinib who had previously received T helper 2 (Th2) biologics but discontinued treatment owing to lack of efficacy (group A) with those who were bio-naive or had discontinued these treatments for reasons other than inefficacy (group B). Methods We conducted a retrospective multicentre study of 524 patients with moderate-to-severe AD treated with upadacitinib. A propensity score-matching method was used for the subanalysis of 316 patients to compare group A and group B. Results A significant clinical improvement starting from week 4 and continuing throughout the study period was observed in the overall population and in both groups A and B. Group B showed greater improvements at later follow-up times, with a higher median Eczema Area and Severity Index (EASI) percentage improvement at week 52 (P = 0.03) and a significantly higher proportion of patients achieving EASI 90 and EASI 100 (representing a ≥ 90% and 100% improvement from baseline, respectively) at week 36 (P =0.02, χ² = 9.5). For the Pruritus Numerical Rating Scale (P-NRS) and Sleep Disturbances Numerical Rating Scale (SD-NRS), group B had a significantly greater percentage of patients reporting a score of 0 or 1 at week 52 (P-NRS: P = 0.02, χ² = 5.7; SD-NRS: P = 0.049, χ² = 3.9). Group B also had a significantly higher percentage of patients reaching minimal disease activity at week 52 (P = 0.01, χ² = 6.0). Conclusions Upadacitinib proved to be effective in the long term not only as a first-line therapy but also in patients with a history of treatment with a biologic that had been unsuccessful. However, patients in group B consistently demonstrated better clinical responses at later follow-ups, suggesting that individuals who are bio-naive and those who discontinued Th2 biologics for reasons other than inefficacy may respond more favourably to upadacitinib.