杜匹单抗对 6 个月至 5 岁特应性皮炎患儿长达 1 年的安全性和有效性:3期开放标签扩展研究结果。

IF 8.6 1区 医学 Q1 DERMATOLOGY
Amy S. Paller, Elaine C. Siegfried, Eric L. Simpson, Michael J. Cork, Robert Sidbury, Iris H. Chen, Faisal A. Khokhar, Jing Xiao, Ariane Dubost-Brama, Ashish Bansal
{"title":"杜匹单抗对 6 个月至 5 岁特应性皮炎患儿长达 1 年的安全性和有效性:3期开放标签扩展研究结果。","authors":"Amy S. Paller,&nbsp;Elaine C. Siegfried,&nbsp;Eric L. Simpson,&nbsp;Michael J. Cork,&nbsp;Robert Sidbury,&nbsp;Iris H. Chen,&nbsp;Faisal A. Khokhar,&nbsp;Jing Xiao,&nbsp;Ariane Dubost-Brama,&nbsp;Ashish Bansal","doi":"10.1007/s40257-024-00859-y","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management.</p><h3>Objectives</h3><p>The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE.</p><h3>Methods</h3><p>In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to &lt; 15 kg: 200 mg; ≥ 15 kg to &lt; 30 kg: 300 mg).</p><h3>Results</h3><p>Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0–5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator’s Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores.</p><h3>Conclusions</h3><p>Consistent with results seen in adults, adolescents, and older children (aged 6–11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":null,"pages":null},"PeriodicalIF":8.6000,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193700/pdf/","citationCount":"0","resultStr":"{\"title\":\"Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study\",\"authors\":\"Amy S. Paller,&nbsp;Elaine C. Siegfried,&nbsp;Eric L. Simpson,&nbsp;Michael J. Cork,&nbsp;Robert Sidbury,&nbsp;Iris H. Chen,&nbsp;Faisal A. Khokhar,&nbsp;Jing Xiao,&nbsp;Ariane Dubost-Brama,&nbsp;Ashish Bansal\",\"doi\":\"10.1007/s40257-024-00859-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management.</p><h3>Objectives</h3><p>The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE.</p><h3>Methods</h3><p>In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to &lt; 15 kg: 200 mg; ≥ 15 kg to &lt; 30 kg: 300 mg).</p><h3>Results</h3><p>Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0–5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator’s Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores.</p><h3>Conclusions</h3><p>Consistent with results seen in adults, adolescents, and older children (aged 6–11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).</p></div>\",\"PeriodicalId\":7706,\"journal\":{\"name\":\"American Journal of Clinical Dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2024-05-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193700/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/s40257-024-00859-y\",\"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/s40257-024-00859-y","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:患有中度至重度特应性皮炎(AD)的儿童患者通常疾病负担较重,且病情持续存在的风险较高。尽管存在持续使用安全性不佳和停药后复发风险的问题,但标准的免疫抑制系统治疗一直被用于儿童特应性皮炎的标示外治疗。生物制剂 dupilumab 是首个获准用于 6 个月大儿童中度至重度 AD 的全身治疗药物。我们需要这一患者群体的长期安全性和疗效数据,以便为持续性 AD 管理提供依据:这项工作的目的是在一项开放标签扩展(OLE)研究[LIBERTY AD PED-OLE(NCT02612454)]中,确定6个月至5岁中重度AD儿童接受长达1年的dupilumab治疗的长期安全性和疗效,这些儿童之前参加了为期16周的双盲3期LIBERTY AD PRESCHOOL试验(NCT03346434 B部分;母研究),随后被纳入PED-OLE:在PED-OLE中,患者按照体重阶梯疗法(体重≥5 kg至<15 kg:200 mg;≥15 kg至<30 kg:300 mg)每4周接受一次dupilumab治疗:对142名患者的数据进行了分析,其中60名患者在数据库锁定时已完成52周的访问。基线时的平均年龄为 4.1 岁 [SD, 1.13; range, 1.0-5.9 years]。大多数患者(78.2%)报告了≥1次治疗突发不良事件(TEAE),其中大多数为轻度或中度,且为一过性。最常报告的 TEAE 为鼻咽炎(19.7%)、咳嗽(15.5%)和发热(14.1%)。有 1 例 TEAE 导致停药(严重荨麻疹,1 天后缓解)。到第52周时,36.2%的患者的研究者总体评估得分达到0/1(皮肤清澈/几乎清澈),96.6%、79.3%和58.6%的患者的湿疹面积和严重程度指数得分分别至少改善了50%、75%或90%:与在成人、青少年和年龄较大的儿童(6-11 岁)身上看到的结果一致,对于 6 个月至 5 岁中度至重度 AD 控制不佳的儿童,使用杜比单抗长达 1 年的治疗显示出了可接受的长期安全性和持续疗效。这些结果支持在这一患者群体中长期持续使用dupilumab:试验注册:ClinicalTrials.gov Identifiers:试验注册:ClinicalTrials.gov Identifiers:NCT02612454 和 NCT03346434(B 部分)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study

Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study

Background

Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management.

Objectives

The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE.

Methods

In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg).

Results

Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0–5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator’s Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores.

Conclusions

Consistent with results seen in adults, adolescents, and older children (aged 6–11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population.

Trial Registration

ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

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.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信