528 - Rapid skin clearance and itch improvement with upadacitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: results from a phase 3b head-to-head clinical trial (Heads Up)

Abstract Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, inflammatory disease characterized by multiple skin manifestations and intense itching that can impact patient quality of life. The effect of upadacitinib (UPA) and dupilumab (DUP) was evaluated in a double-blind, double-dummy, head-to-head phase 3b clinical trial (Heads Up; NCT03738397) of adult patients (age: 18-75 years) with moderate-to-severe AD (Eczema Area and Severity Index [EASI] ≥16; body surface area ≥10%; validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) ≥3 at screening and baseline; Worst Pruritus Numerical Rating Scale [WP-NRS] ≥4 at baseline) randomized 1:1 to UPA 30 mg orally once-daily (N=348) or DUP 300 mg subcutaneous injection every two weeks after a 600 mg loading dose (N=344). Objective The effects of UPA and DUP on skin clearance and itch improvement are reported here. Methods Skin clearance was assessed by EASI, with response defined as an improvement ≥75% (EASI75), ≥90% (EASI90), and 100% (EASI100) from baseline. Itch intensity was assessed daily by WP-NRS up to week 16, then at study visits up to week 24. Weekly WP-NRS scores were analyzed as a 7-day rolling average up to week 16, then at study visits through week 24. Daily WP-NRS scores were analyzed day-to-day through day 28. Mean percent improvement and the proportion of patients achieving clinically meaningful improvement (≥4-point improvement from baseline) were evaluated. The proportion of patients achieving a state of no/minimal itch (defined as WP-NRS score of 0/1) was evaluated as a post-hoc analysis. Results EASI75/90/100 response rates were significantly greater with UPA versus DUP at week 16 (UPA = 72.4%/61.6%/28.4%, DUP = 62.6%/40.3%/7.9%; P<0.01 for all comparisons), with greater EASI75 and EASI90 rates observed with UPA as early as week 1 (nominal P<0.05). Mean percent improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 67.8%, DUP= 49.6%; P<0.001), with greater improvement observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater mean percent improvement with UPA versus DUP as early as day 2, the day after the first dose (UPA = 22.0%, DUP = 4.2%; nominal P<0.001). The proportion of patients that achieved clinically meaningful improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 56.1%, DUP = 36.4%; P<0.001), with greater proportions observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater proportion of patients achieved clinically meaningful improvement with UPA versus DUP as early as day 2 (UPA = 15.3%, DUP = 3.4%; nominal P<0.001). The proportion of patients that achieved a state of no/minimal itch based on weekly WP-NRS was greater with UPA versus DUP at week 16 (UPA = 35.5%, DUP = 16.2%; nominal P<0.001) and at week 1 (nominal P<0.001). Conclusions Skin clearance and itch improvement were consistently better with UPA compared with DUP in adult patients with moderate-to-severe AD, with greater improvements observed as early as week 1 for skin clearance and the day following treatment for itch improvement.

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