Efficacy and Safety of Upadacitinib in Patients With Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results Through 140 Weeks.

Abstract

Background: Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe atopic dermatitis (AD) in adults and adolescents; long-term efficacy and safety data beyond 1 year are needed.

Objective: The aim was to evaluate the long-term efficacy and safety of upadacitinib treatment through 140 weeks in patients with moderate-to-severe AD.

Methods: Measure Up 1 (MeUp1; NCT03569293), Measure Up 2 (MeUp2; NCT03607422), and AD Up (NCT03568318) are ongoing, phase 3, randomized clinical trials evaluating upadacitinib 15 mg (UPA15) and 30 mg (UPA30) in adults and adolescents with moderate-to-severe AD. This interim analysis evaluated efficacy and safety through week 140. At baseline, patients were randomized 1:1:1 to receive once-daily UPA15, UPA30, or placebo alone (MeUp1/2) or with concomitant topical corticosteroids (AD Up). At week 16, patients initially randomized to placebo were rerandomized 1:1 to UPA15 or UPA30. Skin and itch efficacy assessments included achievement of ≥ 75%/≥ 90%/100% improvement from baseline in Eczema Area and Severity Index (EASI 75/90/100), validated Investigator Global Assessment for AD score of clear/almost clear (vIGA-AD 0/1), and ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (∆WP-NRS≥4). Safety assessments included incidence of treatment-emergent adverse events.

Results: A total of 2782 patients were randomized in MeUp1/2 or AD Up. Efficacy response rates, including optimal outcomes such as EASI 90 and WP-NRS score of 0/1, were sustained through week 140 in all three studies. At week 140, EASI 75 was achieved by 85.5%/90.5% (UPA15/UPA30; integrated MeUp1/2) and 81.5%/90.0% (UPA15/UPA30; AD Up) of patients, and vIGA-AD 0/1 was achieved by 56.6%/64.4% (UPA15/UPA30; integrated MeUp1/2) and 52.0%/56.8% (UPA15/UPA30; AD Up) of patients. Over 60% of patients across all three studies achieved ∆WP-NRS≥4 at week 140. Pooled safety data across all three studies demonstrated safety profiles consistent with 16-week and 52-week analyses.

Conclusions: UPA15 and UPA30 with and without topical corticosteroids demonstrated robust, durable efficacy and a favorable safety profile through 140 weeks in adults and adolescents with moderate-to-severe AD.

Trial registration: Measure Up 1 (NCT03569293; https://clinicaltrials.gov/study/NCT03569293 ), Measure Up 2 (NCT03607422; https://clinicaltrials.gov/study/NCT03607422 ), and AD Up (NCT03568318; https://clinicaltrials.gov/study/NCT03568318 ).