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.
Eric L Simpson, Jonathan I Silverberg, Vimal H Prajapati, Kilian Eyerich, Norito Katoh, Mark Boguniewicz, Emma Guttman-Yassky, E James Song, Wan-Ju Lee, Henrique D Teixeira, Tianshuang Wu, Cristina Sancho Sanchez, Namita Vigna, Brian M Calimlim, Marjolein de Bruin-Weller
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引用次数: 0
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).
期刊介绍：
Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers.
The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.
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