Amy S Paller, Pedro Mendes-Bastos, Elaine Siegfried, Lawrence F Eichenfield, Weily Soong, Vimal H Prajapati, Peter Lio, Eric L Simpson, Eliza M Raymundo, Smitha Suravaram, Xiaofei Hu, Yang Yang, Xiaohong Huang, Brian M Calimlim, Andrew M Platt, John C Su, Min Zheng, Kiwako Yamamoto-Hanada, Henrique D Teixeira, Alan D Irvine
{"title":"乌达帕替尼治疗中重度特应性皮炎青少年：对 3 项为期 76 周的 3 期随机临床试验的分析。","authors":"Amy S Paller, Pedro Mendes-Bastos, Elaine Siegfried, Lawrence F Eichenfield, Weily Soong, Vimal H Prajapati, Peter Lio, Eric L Simpson, Eliza M Raymundo, Smitha Suravaram, Xiaofei Hu, Yang Yang, Xiaohong Huang, Brian M Calimlim, Andrew M Platt, John C Su, Min Zheng, Kiwako Yamamoto-Hanada, Henrique D Teixeira, Alan D Irvine","doi":"10.1001/jamadermatol.2024.3696","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available.</p><p><strong>Objective: </strong>To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks.</p><p><strong>Design, setting, and participants: </strong>The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. Data were collected from August 2018 to April 2022, and data were analyzed from June 2022 to September 2023.</p><p><strong>Interventions: </strong>Adolescents were randomized 1:1:1 to receive once-daily oral upadacitinib, 15 mg; upadacitinib, 30 mg; or placebo, either alone (Measure Up 1 and Measure Up 2 trials) or with topical corticosteroids (AD Up). At week 16, placebo-treated patients were rerandomized to receive upadacitinib, 15 mg, or upadacitinib, 30 mg, daily.</p><p><strong>Main outcomes and measures: </strong>Coprimary end points assessing efficacy included achievement of 75% reduction or more in the Eczema Area and Severity Index Score (EASI-75) from baseline, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with 2 grades or more of improvement, and Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater through week 76 for participants with a WP-NRS score of 4 points or higher at baseline.</p><p><strong>Results: </strong>From all studies, 542 adolescents were included; of these, 284 (52.4%) were female. At week 76, among patients in the Measure Up 1, Measure Up 2, and AD Up trials, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking upadacitinib, 15 mg, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking upadacitinib, 30 mg, indicating maintenance or improvement of EASI-75 across 76 weeks with upadacitinib. Efficacy measured by achievement of vIGA-AD score of 0 or 1 and WP-NRS improvement of 4 points or more from baseline was similarly maintained or improved through week 76 for adolescents taking upadacitinib, 15 mg or 30 mg. Long-term outcomes in Measure Up 1, Measure Up 2, and AD Up participants were consistent with the known adverse event profile of upadacitinib (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years); no new signals were observed with either dose.</p><p><strong>Conclusions and relevance: </strong>In this study assessing 3 randomized clinical trials, long-term treatment of adolescents with moderate to severe AD with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 76 weeks.</p><p><strong>Trial registrations: </strong>Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581505/pdf/","citationCount":"0","resultStr":"{\"title\":\"Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis: Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks.\",\"authors\":\"Amy S Paller, Pedro Mendes-Bastos, Elaine Siegfried, Lawrence F Eichenfield, Weily Soong, Vimal H Prajapati, Peter Lio, Eric L Simpson, Eliza M Raymundo, Smitha Suravaram, Xiaofei Hu, Yang Yang, Xiaohong Huang, Brian M Calimlim, Andrew M Platt, John C Su, Min Zheng, Kiwako Yamamoto-Hanada, Henrique D Teixeira, Alan D Irvine\",\"doi\":\"10.1001/jamadermatol.2024.3696\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available.</p><p><strong>Objective: </strong>To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks.</p><p><strong>Design, setting, and participants: </strong>The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. 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引用次数: 0
摘要
重要性：Measure Up 1、Measure Up 2和AD Up研究证明了高达替尼对成人和青少年特应性皮炎（AD）患者52周的疗效和不良反应；然而，此前尚未获得青少年的长期疗效（超过1年）：目的：评估高达替尼对中重度特应性皮炎青少年患者76周的疗效和不良反应：Measure Up 1、Measure Up 2和AD Up试验是正在进行的双盲、安慰剂对照3期随机临床试验，包括中度至重度AD青少年（12至17岁）。数据收集时间为2018年8月至2022年4月，数据分析时间为2022年6月至2023年9月：青少年按1:1:1的比例随机接受每日一次的口服达帕替尼（15毫克）、达帕替尼（30毫克）或安慰剂，可单独使用（Measure Up 1和Measure Up 2试验）或与局部皮质类固醇一起使用（AD Up）。第16周时，安慰剂治疗患者被重新随机分配到每天接受15毫克或30毫克的达帕西替尼治疗：评估疗效的主要终点包括：湿疹面积和严重程度指数评分（EASI-75）比基线降低75%或以上；特应性皮炎研究者全球评估（vIGA-AD）评分为 "无"（0）或 "基本无"（1），且有2级或以上的改善；基线时WP-NRS评分为4分或以上的参与者，第76周时最严重瘙痒数字评定量表（WP-NRS）评分改善4分或以上：所有研究共纳入了 542 名青少年，其中 284 名（52.4%）为女性。第76周时，在Measure Up 1、Measure Up 2和AD Up试验的患者中，服用15毫克达帕替尼的青少年中分别有89.1%、84.4%和87.8%达到了EASI-75，服用30毫克达帕替尼的青少年中分别有96.1%、93.6%和82.7%达到了EASI-75，这表明服用达帕替尼76周后EASI-75得到了维持或改善。服用达帕替尼（15 毫克或 30 毫克）的青少年在第 76 周时，vIGA-AD 评分达到 0 分或 1 分，WP-NRS 从基线提高 4 分或更多，以此衡量疗效，也同样得到了维持或改善。Measure Up 1、Measure Up 2 和 AD Up 参与者的长期结果与已知的奥达帕替尼不良反应情况一致（疱疹病毒感染：每 100 患者年分别有 4.0、1.9 和 1.1 例；肌酸激酶升高：结论和相关性：在这项评估3项随机临床试验的研究中，奥达帕替尼对中重度AD青少年的长期治疗显示出良好的获益-风险特征，疗效反应可持续76周：Measure Up 1 试验：试验注册：Measure Up 1 试验：ClinicalTrials.gov Identifier：NCT03569293; Measure Up 2试验：NCT03607422; AD Up试验：NCT03568318。
Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis: Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks.
Importance: The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available.
Objective: To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks.
Design, setting, and participants: The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. Data were collected from August 2018 to April 2022, and data were analyzed from June 2022 to September 2023.
Interventions: Adolescents were randomized 1:1:1 to receive once-daily oral upadacitinib, 15 mg; upadacitinib, 30 mg; or placebo, either alone (Measure Up 1 and Measure Up 2 trials) or with topical corticosteroids (AD Up). At week 16, placebo-treated patients were rerandomized to receive upadacitinib, 15 mg, or upadacitinib, 30 mg, daily.
Main outcomes and measures: Coprimary end points assessing efficacy included achievement of 75% reduction or more in the Eczema Area and Severity Index Score (EASI-75) from baseline, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with 2 grades or more of improvement, and Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater through week 76 for participants with a WP-NRS score of 4 points or higher at baseline.
Results: From all studies, 542 adolescents were included; of these, 284 (52.4%) were female. At week 76, among patients in the Measure Up 1, Measure Up 2, and AD Up trials, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking upadacitinib, 15 mg, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking upadacitinib, 30 mg, indicating maintenance or improvement of EASI-75 across 76 weeks with upadacitinib. Efficacy measured by achievement of vIGA-AD score of 0 or 1 and WP-NRS improvement of 4 points or more from baseline was similarly maintained or improved through week 76 for adolescents taking upadacitinib, 15 mg or 30 mg. Long-term outcomes in Measure Up 1, Measure Up 2, and AD Up participants were consistent with the known adverse event profile of upadacitinib (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years); no new signals were observed with either dose.
Conclusions and relevance: In this study assessing 3 randomized clinical trials, long-term treatment of adolescents with moderate to severe AD with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 76 weeks.
Trial registrations: Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.
期刊介绍：
JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery.
JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care.
The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists.
JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.
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