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
{"title":"Upadacitinib与安慰剂（Measure Up 1和Measure Up 2）和Dupilumab （Heads Up）相比，快速改善瘙痒和皮肤清除：来自中重度特应性皮炎患者的三个3期临床试验的结果。","authors":"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","doi":"10.1007/s13555-025-01443-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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).</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov; NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03738397 (Heads Up).</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1007/s13555-025-01443-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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).</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov; NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03738397 (Heads Up).</p>\",\"PeriodicalId\":11186,\"journal\":{\"name\":\"Dermatology and Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-06-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Dermatology and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13555-025-01443-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dermatology and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13555-025-01443-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
实现严格的结局（例如，湿疹面积和严重程度指数[EASI 90]较基线改善≥90%，或最严重瘙痒数值评定量表[WP-NRS 0/1]从最小痒到无痒）与特应性皮炎（AD）患者生活质量的显着改善相关。采用严格的结局，我们在三个3期临床试验中评估了upadacitinib与安慰剂和dupilumab对中重度AD患者快速瘙痒改善和皮肤清除的疗效。方法：在Measure Up 1和Measure Up 2中，患者接受口服upadacitinib 15 mg （UPA15）、30 mg （UPA30）或安慰剂，每天1次，持续16周；在Heads Up中，患者每天口服UPA30 1次，或每2周皮下注射300 mg杜匹单抗（在600 mg负荷剂量后），持续24周。主要结局包括达到WP-NRS 0/1、WP-NRS 0、EASI 90和EASI 100的患者比例，以及达到综合结局(EASI 90和WP-NRS 0/1；EASI 100和WP-NRS 0)。患者在前16周每天评估WP-NRS，并在之后的预定访问中评估，研究者在预定访问中评估EASI。结论：与接受安慰剂或杜匹单抗治疗的患者相比，接受upadacitinib治疗的中重度AD患者迅速达到了严格的瘙痒改善和皮肤清除目标，其反应持续到第16周（Measure Up 1和Measure Up 2）和24周（Heads Up）。临床试验注册：ClinicalTrials.gov；NCT03569293（向上测量1），NCT03607422（向上测量2）和NCT03738397（向上测量）。
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.
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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