Tralokinumab在第16周为未达到IGA0/1的中度至重度特应性皮炎成年人提供有临床意义的反应。

IF 8.6 1区 医学 Q1 DERMATOLOGY American Journal of Clinical Dermatology Pub Date : 2023-10-07 DOI:10.1007/s40257-023-00817-0
Eric L. Simpson, Andrew Blauvelt, Jonathan I. Silverberg, Michael J. Cork, Norito Katoh, Thomas Mark, Shannon K. R. Schneider, Andreas Wollenberg
{"title":"Tralokinumab在第16周为未达到IGA0/1的中度至重度特应性皮炎成年人提供有临床意义的反应。","authors":"Eric L. Simpson,&nbsp;Andrew Blauvelt,&nbsp;Jonathan I. Silverberg,&nbsp;Michael J. Cork,&nbsp;Norito Katoh,&nbsp;Thomas Mark,&nbsp;Shannon K. R. Schneider,&nbsp;Andreas Wollenberg","doi":"10.1007/s40257-023-00817-0","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and Objective</h3><p>Investigator’s Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2.</p><h3>Methods</h3><p>This post hoc analysis included patients (<i>n</i> = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16.</p><h3>Results</h3><p>Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%).</p><h3>Conclusions</h3><p>Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available]</p><h3>Clinical Trial Registration</h3><p>NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019.</p>\n<div><div><div></div></div><div><p><b>Video abstract:</b> Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB)</p></div></div></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":null,"pages":null},"PeriodicalIF":8.6000,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796753/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tralokinumab Provides Clinically Meaningful Responses at Week 16 in Adults with Moderate-to-Severe Atopic Dermatitis Who Do Not Achieve IGA 0/1\",\"authors\":\"Eric L. Simpson,&nbsp;Andrew Blauvelt,&nbsp;Jonathan I. Silverberg,&nbsp;Michael J. Cork,&nbsp;Norito Katoh,&nbsp;Thomas Mark,&nbsp;Shannon K. R. Schneider,&nbsp;Andreas Wollenberg\",\"doi\":\"10.1007/s40257-023-00817-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and Objective</h3><p>Investigator’s Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2.</p><h3>Methods</h3><p>This post hoc analysis included patients (<i>n</i> = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16.</p><h3>Results</h3><p>Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%).</p><h3>Conclusions</h3><p>Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available]</p><h3>Clinical Trial Registration</h3><p>NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019.</p>\\n<div><div><div></div></div><div><p><b>Video abstract:</b> Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB)</p></div></div></div>\",\"PeriodicalId\":7706,\"journal\":{\"name\":\"American Journal of Clinical Dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2023-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796753/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Clinical Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s40257-023-00817-0\",\"RegionNum\":1,\"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":"American Journal of Clinical Dermatology","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s40257-023-00817-0","RegionNum":1,"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

背景和目的:研究者对透明/几乎透明皮肤的全球评估(IGA 0/1)是慢性中重度特应性皮炎短期治疗后难以实现的终点,并且不能完全反映其他参数的临床意义变化。我们使用两项单药治疗III期试验(ECZTRA 1和2)的汇总数据,评估了曲洛单抗与安慰剂对第16周未达到IGA 0/1的患者其他有临床意义参数的影响。评估特应性皮炎程度和严重程度的终点包括湿疹面积和严重程度指数(EASI-50/75/90)达到IGA0/1、50%、75%和90%改善的患者比例;评估患者报告结果的终点包括每日最严重瘙痒数值评定量表(NRS)改善≥3分,湿疹相关睡眠干扰(睡眠)NRS改善≥3点,皮肤科生活质量指数(DLQI)改善≥4分,DLQI≤5。具体而言,有临床意义的反应被定义为EASI-50,瘙痒NRS改善≥3点,或DLQI改善≥4点,瘙痒NRS改善≥3分(22.6%对9.4%),或DLQI改善≥4分(41.2%对24.5%)。与安慰剂相比,在数字上,接受曲洛单抗治疗的患者中,有更大比例的患者实现了所有三项有临床意义的反应(30%对18%)或至少一项结果发生了临床意义的变化(48.8%对28.5%),如EASI-75(13.5%vs 4.1%)、EASI-90(3.5%vs 1.1%)、DLQI≤5(22.5%vs 12.5%)和睡眠NRS≥3点改善(24.5%vs 11.5%)。使用疗效和生活质量的多个经验证的结果测量,以及IGA评分,可以更好地描述曲洛单抗对中重度特应性皮炎患者的治疗反应。[视频摘要可用]临床试验注册:NCT03131648(ECZTRA 1);研究开始日期:2017年5月30日;初步竣工日期:2018年8月7日;研究完成日期:2019年10月10日。NCT03160885(ECZTRA 2);研究开始日期:2017年6月12日;初步竣工日期:2019年9月4日;研究完成日期:2019年8月14日。视频摘要:曲洛单抗在第16周为未达到IGA 0/1的中度至重度特应性皮炎成年人提供了有临床意义的反应(MP4 362818 KB)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Tralokinumab Provides Clinically Meaningful Responses at Week 16 in Adults with Moderate-to-Severe Atopic Dermatitis Who Do Not Achieve IGA 0/1

Background and Objective

Investigator’s Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2.

Methods

This post hoc analysis included patients (n = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16.

Results

Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%).

Conclusions

Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available]

Clinical Trial Registration

NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019.

Video abstract: Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB)

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
15.20
自引率
2.70%
发文量
84
审稿时长
>12 weeks
期刊介绍: The American Journal of Clinical Dermatology is dedicated to evidence-based therapy and effective patient management in dermatology. It publishes critical review articles and clinically focused original research covering comprehensive aspects of dermatological conditions. The journal enhances visibility and educational value through features like Key Points summaries, plain language summaries, and various digital elements, ensuring accessibility and depth for a diverse readership.
期刊最新文献
Disseminated Superficial Actinic Porokeratosis: A Systematic Treatment Review. Patient-Reported Hair Loss and Its Impacts as Measured by the Alopecia Areata Patient Priority Outcomes Instrument in Patients Treated with Ritlecitinib: The ALLEGRO Phase 2b/3 Randomized Clinical Trial. From Compression to Itch: Exploring the Link Between Nerve Compression and Neuropathic Pruritus. Authors’ Reply to Wang et al., “Comment on ‘Efficacy and Safety of Brodalumab, an Anti‑interleukin‑17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16‑Week Results of a Randomized Clinical Trial’” Comment on “Efficacy and Safety of Brodalumab, an Anti‑interleukin‑17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16‑Week Results of a Randomized Clinical Trial”
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1