抗IL-13Rα1抗体Eblasakimab能降低中重度特应性皮炎患者与特应相关的血清生物标志物。

IF 5.4 2区 医学 Q1 IMMUNOLOGY BioDrugs Pub Date : 2024-11-01 Epub Date: 2024-10-15 DOI:10.1007/s40259-024-00685-y
Ferda Cevikbas, Alison Ward, Karen A Veverka
{"title":"抗IL-13Rα1抗体Eblasakimab能降低中重度特应性皮炎患者与特应相关的血清生物标志物。","authors":"Ferda Cevikbas, Alison Ward, Karen A Veverka","doi":"10.1007/s40259-024-00685-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Eblasakimab, a first-in-class monoclonal antibody with a unique mechanism to target the interleukin (IL)-13 receptor alpha 1 (IL-13Rα1), inhibits IL-4/IL-13 signaling in the pathophysiology of atopic dermatitis (AD). This study investigates the impact of eblasakimab on type 2 inflammatory biomarkers in patients with moderate-to-severe AD.</p><p><strong>Methods: </strong>A double‑blind, multiple ascending dose, phase Ib study evaluated the effect of eblasakimab (200, 400, 600 mg) or placebo administered subcutaneously once weekly for 8 weeks in patients with moderate‑to‑severe AD. Serum levels of thymus and activation-regulated chemokine (TARC), total immunoglobulin E (IgE), and lactate dehydrogenase (LDH) were assessed.</p><p><strong>Results: </strong>Eblasakimab suppressed TARC, IgE, and LDH in the 400-mg and 600-mg groups over 8 weeks of treatment. Patients in the 400-mg and 600-mg groups experienced a reduction of 72.8% (p = 0.004) and 62.9% (p = 0.003), respectively, for TARC, 35.1% (p = 0.006) and 20.9% (not significant; NS), respectively, for IgE, and 24.6% (NS) and 23.1% (NS), respectively, for LDH between baseline and Week 8. Reduction in serum TARC in the 400-mg group was significantly greater than placebo as early as Week 1, whereas reductions in total IgE were more gradual. Serum TARC and total IgE remained suppressed in the 400-mg and 600-mg eblasakimab groups for 4-6 weeks following the last administered dose.</p><p><strong>Conclusion: </strong>The effect of eblasakimab on circulating AD‑associated biomarker levels was accompanied by improvements in signs and symptoms of AD, consistent with the inhibition of IL-13 and IL-4 signaling via the type 2 receptor.</p><p><strong>Trial registration number: </strong>NCT04090229.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"821-830"},"PeriodicalIF":5.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530511/pdf/","citationCount":"0","resultStr":"{\"title\":\"Eblasakimab, an Anti-IL‑13Rα1 Antibody, Reduces Atopy-Associated Serum Biomarkers in Moderate‑to‑Severe Atopic Dermatitis.\",\"authors\":\"Ferda Cevikbas, Alison Ward, Karen A Veverka\",\"doi\":\"10.1007/s40259-024-00685-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Eblasakimab, a first-in-class monoclonal antibody with a unique mechanism to target the interleukin (IL)-13 receptor alpha 1 (IL-13Rα1), inhibits IL-4/IL-13 signaling in the pathophysiology of atopic dermatitis (AD). This study investigates the impact of eblasakimab on type 2 inflammatory biomarkers in patients with moderate-to-severe AD.</p><p><strong>Methods: </strong>A double‑blind, multiple ascending dose, phase Ib study evaluated the effect of eblasakimab (200, 400, 600 mg) or placebo administered subcutaneously once weekly for 8 weeks in patients with moderate‑to‑severe AD. Serum levels of thymus and activation-regulated chemokine (TARC), total immunoglobulin E (IgE), and lactate dehydrogenase (LDH) were assessed.</p><p><strong>Results: </strong>Eblasakimab suppressed TARC, IgE, and LDH in the 400-mg and 600-mg groups over 8 weeks of treatment. Patients in the 400-mg and 600-mg groups experienced a reduction of 72.8% (p = 0.004) and 62.9% (p = 0.003), respectively, for TARC, 35.1% (p = 0.006) and 20.9% (not significant; NS), respectively, for IgE, and 24.6% (NS) and 23.1% (NS), respectively, for LDH between baseline and Week 8. Reduction in serum TARC in the 400-mg group was significantly greater than placebo as early as Week 1, whereas reductions in total IgE were more gradual. Serum TARC and total IgE remained suppressed in the 400-mg and 600-mg eblasakimab groups for 4-6 weeks following the last administered dose.</p><p><strong>Conclusion: </strong>The effect of eblasakimab on circulating AD‑associated biomarker levels was accompanied by improvements in signs and symptoms of AD, consistent with the inhibition of IL-13 and IL-4 signaling via the type 2 receptor.</p><p><strong>Trial registration number: </strong>NCT04090229.</p>\",\"PeriodicalId\":9022,\"journal\":{\"name\":\"BioDrugs\",\"volume\":\" \",\"pages\":\"821-830\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530511/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BioDrugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40259-024-00685-y\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioDrugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40259-024-00685-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

简介依巴沙基单抗是一种首创的单克隆抗体,具有靶向白细胞介素(IL)-13受体α1(IL-13Rα1)的独特机制,可抑制特应性皮炎(AD)病理生理学中的IL-4/IL-13信号传导。本研究探讨了依巴单抗对中重度特应性皮炎患者2型炎症生物标志物的影响:一项双盲、多剂量递增的Ib期研究评估了依巴单抗(200、400、600毫克)或安慰剂对中重度AD患者皮下注射的影响,每周一次,共8周。研究评估了胸腺和活化调节趋化因子(TARC)、总免疫球蛋白E(IgE)和乳酸脱氢酶(LDH)的血清水平:在为期8周的治疗中,易拉西单抗抑制了400毫克组和600毫克组的TARC、IgE和LDH。从基线到第8周,400毫克组和600毫克组患者的TARC分别降低了72.8%(p = 0.004)和62.9%(p = 0.003),IgE分别降低了35.1%(p = 0.006)和20.9%(无显著性;NS),LDH分别降低了24.6%(NS)和23.1%(NS)。早在第 1 周,400 毫克组血清 TARC 的降幅就明显高于安慰剂,而总 IgE 的降幅则较为缓慢。在最后一次给药后的4-6周内,400毫克和600毫克依布拉西单抗组的血清TARC和总IgE仍受到抑制:eblasakimab对循环AD相关生物标志物水平的影响伴随着AD体征和症状的改善,这与通过2型受体抑制IL-13和IL-4信号传导是一致的:NCT04090229.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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
Eblasakimab, an Anti-IL‑13Rα1 Antibody, Reduces Atopy-Associated Serum Biomarkers in Moderate‑to‑Severe Atopic Dermatitis.

Introduction: Eblasakimab, a first-in-class monoclonal antibody with a unique mechanism to target the interleukin (IL)-13 receptor alpha 1 (IL-13Rα1), inhibits IL-4/IL-13 signaling in the pathophysiology of atopic dermatitis (AD). This study investigates the impact of eblasakimab on type 2 inflammatory biomarkers in patients with moderate-to-severe AD.

Methods: A double‑blind, multiple ascending dose, phase Ib study evaluated the effect of eblasakimab (200, 400, 600 mg) or placebo administered subcutaneously once weekly for 8 weeks in patients with moderate‑to‑severe AD. Serum levels of thymus and activation-regulated chemokine (TARC), total immunoglobulin E (IgE), and lactate dehydrogenase (LDH) were assessed.

Results: Eblasakimab suppressed TARC, IgE, and LDH in the 400-mg and 600-mg groups over 8 weeks of treatment. Patients in the 400-mg and 600-mg groups experienced a reduction of 72.8% (p = 0.004) and 62.9% (p = 0.003), respectively, for TARC, 35.1% (p = 0.006) and 20.9% (not significant; NS), respectively, for IgE, and 24.6% (NS) and 23.1% (NS), respectively, for LDH between baseline and Week 8. Reduction in serum TARC in the 400-mg group was significantly greater than placebo as early as Week 1, whereas reductions in total IgE were more gradual. Serum TARC and total IgE remained suppressed in the 400-mg and 600-mg eblasakimab groups for 4-6 weeks following the last administered dose.

Conclusion: The effect of eblasakimab on circulating AD‑associated biomarker levels was accompanied by improvements in signs and symptoms of AD, consistent with the inhibition of IL-13 and IL-4 signaling via the type 2 receptor.

Trial registration number: NCT04090229.

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
BioDrugs
BioDrugs 医学-免疫学
CiteScore
12.60
自引率
2.90%
发文量
50
审稿时长
>12 weeks
期刊介绍: An essential resource for R&D professionals and clinicians with an interest in biologic therapies. BioDrugs covers the development and therapeutic application of biotechnology-based pharmaceuticals and diagnostic products for the treatment of human disease. BioDrugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.
期刊最新文献
Effect of Biological Therapy for Psoriasis on the Development of Psoriatic Arthritis: A Population-Based Cohort Study. Biochemical Amenability in Fabry Patients Under Chaperone Therapy-How and When to Test? Introducing the Biosimilar Paradigm to Neurology: The Totality of Evidence for the First Biosimilar Natalizumab. Patient Satisfaction and Experience with CT-P17 Following Transition from Reference Adalimumab or Another Adalimumab Biosimilar: Results from the Real-World YU-MATTER Study. Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects.
×
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