Efficacy of Upadacitinib vs Dupilumab Treatment for Moderate‑to‑Severe Atopic Dermatitis: Analysis of Time Spent in Response State From the Level Up Study

Abstract

Introduction & Objectives: Upadacitinib (UPA), a selective oral Janus kinase (JAK) inhibitor, and dupilumab (DUPI), a monoclonal antibody targeting interleukin-4Rα, are both treatments approved for patients with moderate-to-severe Atopic Dermatitis (AD). Results from a phase 3b/4 trial (Level Up NCT05601882) indicated that UPA was superior to DUPI in simultaneously achieving the stringent endpoints of Eczema Area and Severity Index (EASI) improvement of ≥90% from baseline (EASI 90) and a Worst Pruritus Numerical Rating Scale score of 0/1 (WP-NRS 0/1) at Week 16. In this post-hoc analysis, we analyzed the median time (days) spent in response states based on EASI 90 and/or WP-NRS 0/1 in patients either receiving UPA or DUPI over a 16-week period.

Materials & Methods: The Level Up study was a phase 3b/4 head-to-head global, randomized, open-label, efficacy assessor blinded, multicenter study comparing UPA vs DUPI in adolescents and adults with moderate-to-severe AD. Patients were randomized to UPA 15 mg or DUPI per its label for 16 weeks of treatment. Patients on UPA 15 mg were dose-escalated to 30 mg starting at Week 4 if they had a <EASI 50 response, or a <4-point WP-NRS improvement from baseline. Patients taking UPA 15 mg who did not achieve EASI 75 starting at Week 8 similarly had their dose increased to 30 mg. Starting at Week 4, rescue with topical therapy was optional and per investigator’s discretion if protocol criteria were met. The current analyses assessed the number and proportion of days patients spent with clear or nearly-clear skin (EASI 90) and/or no/minimal itch (WP-NRS 0/1), with comparisons made at the median (50th percentile) and upper quartile (75th percentile). Missing data at study visits were imputed using non-responder imputation with multiple imputations.

Results: Participants included 458 patients receiving UPA and 462 receiving DUPI. Cumulatively over a course of 16 weeks, patients taking UPA vs DUPI spent a greater number of days at EASI 90 and WP-NRS 0/1. Over 16 weeks (112 days), 1 in 2 patients (ie, median or 50th-percentile) spent at least 28.0 days at EASI 90 with UPA vs 0 days with DUPI, while 1 in 4 patients spent at least 64.4 days with UPA vs

25.7 days with DUPI. For days at WP-NRS 0/1 with UPA vs DUPI, 1 in 2 patients spent at least 11.3 vs 0.4 days with no/minimal itch respectively; and 1 in 4 patients (ie, upper quartile or 75th-percentile) spent at least 57.2 vs 17.0 days with UPA vs DUPI, respectively. Similar patterns were observed in the number of days simultaneously achieving both EASI 90 and WP-NRS 0/1, as well the proportion of days spent in these responses.

Conclusion: Treatment of moderate-to-severe AD with UPA per label resulted in a greater number or proportion of days spent with EASI 90 and/or WP-NRS 0/1 compared with DUPI over 16 weeks. These results highlight differences in lived day- to-day skin disease and itch symptom burden over the course of treatment and can be used to inform shared decision-making discussions between patients and physicians.