Rapid Itch Relief with Upadacitinib vs Dupilumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: Results from the Phase 3b/4 Level Up Study

Abstract

Introduction Itch is the hallmark symptom of atopic dermatitis (AD). We evaluated itch improvement with upadacitinib (a selective oral Janus kinase inhibitor) vs dupilumab (an injectable monoclonal antibody that inhibits interleukin 4 and interleukin 13 signaling) in patients with moderate-to-severe AD.

Methods In Level Up (NCT05601882), a phase 3b/4, global, open-label, efficacy assessor blinded study, patients (≥12 and <64 years) were randomized 1:1 to receive upadacitinib 15 mg once daily (with potential dose escalation starting Week 4) or dupilumab per label. Itch was assessed daily by the Worst Pruritus Numerical Rating Scale (WP-NRS). This post-hoc analysis evaluated the proportion of patients achieving meaningful itch improvement (WP-NRS reduction ≥4 [∆WP-NRS≥4]) and little-to-no itch (WP-NRS 0 or 1 [WP-NRS 0/1]) among patients with baseline WP-NRS ≥4 and >1, respectively, daily through Day 28 (i.e., prior to potential upadacitinib dose escalation). Non-responder imputation was used to handle missing data. Nominal p-values are reported.

Results A greater proportion of upadacitinib-treated patients (upadacitinib vs dupilumab; nominal p-value) achieved ∆WP-NRS≥4 as early as Day 2 (9.4% vs 3.5%; 0.0003) and increased through Day 28 (50.8% vs 29.3%; <0.0001). A greater proportion of upadacitinib-treated patients achieved WP-NRS 0/1 as early as Day 4 (2.4% vs 0.7%; 0.0329) and increased through Day 28 (18.9% vs 5.7%; <0.0001).

Conclusions More patients treated with upadacitinib 15 mg achieved meaningful itch improvement (as early as the day after treatment initiation) and little-to-no itch (as early as Day 4) compared with dupilumab in this Level Up study.