Rapid Itch Improvement and Skin Clearance with Upadacitinib Versus Placebo (Measure Up 1 and Measure Up 2) and Versus Dupilumab (Heads Up): Results from Three Phase 3 Clinical Trials in Patients with Moderate-to-Severe Atopic Dermatitis.

Abstract

Introduction: Achievement of stringent outcomes (e.g., ≥ 90% improvement from baseline in Eczema Area and Severity Index [EASI 90] or minimal-to-no itch on the Worst Pruritus Numerical Rating Scale [WP-NRS 0/1]) is associated with a substantial improvement in quality of life among patients with atopic dermatitis (AD). Using stringent outcomes, we evaluated the efficacy of upadacitinib vs placebo and vs dupilumab on rapid itch improvement and skin clearance in patients with moderate-to-severe AD in three phase 3 clinical trials.

Methods: Patients received orally administered upadacitinib 15 mg (UPA15), 30 mg (UPA30), or placebo once daily for 16 weeks in Measure Up 1 and Measure Up 2 and orally administered UPA30 once daily or subcutaneously administered 300 mg dupilumab every 2 weeks (after a 600 mg loading dose) for 24 weeks in Heads Up. Key outcomes included the proportion of patients achieving WP-NRS 0/1, WP-NRS 0, EASI 90, and EASI 100, as well as the proportion of patients achieving composite outcomes (EASI 90 and WP-NRS 0/1; EASI 100 and WP-NRS 0). Patients assessed WP-NRS daily for the first 16 weeks and at scheduled visits thereafter, and investigators assessed EASI at scheduled visits.

Results: A greater proportion of patients receiving upadacitinib vs placebo and vs dupilumab achieved WP-NRS 0/1 at week 16 (nominal p < 0.001 vs placebo) and week 24 (nominal p < 0.001 vs dupilumab), with differences as early as the day after treatment initiation (day 2; nominal p < 0.05 vs placebo and vs dupilumab), as well as WP-NRS 0 at week 16 (nominal p < 0.001 vs placebo) and week 24 (nominal p < 0.001 vs dupilumab), with differences as early as day 8 (nominal p < 0.01 vs placebo; nominal p < 0.001 vs dupilumab). A greater proportion of patients receiving upadacitinib vs placebo and vs dupilumab achieved EASI 90 at week 16 (p < 0.001 vs dupilumab), with differences as early as week 1 (nominal p < 0.01 vs placebo; nominal p < 0.05 vs dupilumab), as well as EASI 100 at week 16 (p < 0.001 vs placebo) and week 24 (nominal p < 0.001 vs dupilumab), with differences as early as week 4 (nominal p < 0.001 vs placebo and vs dupilumab). A greater proportion of patients also achieved EASI 90 and WP-NRS 0/1 by week 2 (UPA15: 2.7%, UPA30: 6.7% vs placebo: 0%, nominal p < 0.001; UPA30: 7.1% vs dupilumab: 1.2%, nominal p < 0.001) and EASI 100 and WP-NRS 0 by week 4 (UPA15: 1.6%, UPA30: 3.9% vs placebo: 0.2%, nominal p ≤ 0.01; UPA30: 4.7% vs dupilumab: 0.6%, nominal p < 0.01) through all evaluated time points.

Conclusions: Patients with moderate-to-severe AD treated with upadacitinib rapidly achieved stringent itch improvement and skin clearance targets compared with those receiving placebo or dupilumab, with responses sustained through weeks 16 (Measure Up 1 and Measure Up 2) and 24 (Heads Up).

Clinical trial registration: ClinicalTrials.gov; NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03738397 (Heads Up).