Elevated mepolizumab levels in patients with severe asthma responsive to 1 year’s mepolizumab treatment

Takayasu Nishimaki MD , Hitoshi Sasano MD, PhD , Sonoko Harada PhD , Tomohito Takeshige MD, PhD , Yuuki Sandhu MD, PhD , Yuki Tanabe MD , Kei Matsuno MD, PhD , Tetsutaro Nagaoka MD, PhD , Jun Ito MD, PhD , Ryo Atsuta MD, PhD , Mayu Ohuchi PhD , Shigehiro Yagishita MD, PhD , Akinobu Hamada PhD , Kazuhisa Takahashi MD, PhD , Norihiro Harada MD, PhD
{"title":"Elevated mepolizumab levels in patients with severe asthma responsive to 1 year’s mepolizumab treatment","authors":"Takayasu Nishimaki MD ,&nbsp;Hitoshi Sasano MD, PhD ,&nbsp;Sonoko Harada PhD ,&nbsp;Tomohito Takeshige MD, PhD ,&nbsp;Yuuki Sandhu MD, PhD ,&nbsp;Yuki Tanabe MD ,&nbsp;Kei Matsuno MD, PhD ,&nbsp;Tetsutaro Nagaoka MD, PhD ,&nbsp;Jun Ito MD, PhD ,&nbsp;Ryo Atsuta MD, PhD ,&nbsp;Mayu Ohuchi PhD ,&nbsp;Shigehiro Yagishita MD, PhD ,&nbsp;Akinobu Hamada PhD ,&nbsp;Kazuhisa Takahashi MD, PhD ,&nbsp;Norihiro Harada MD, PhD","doi":"10.1016/j.jacig.2025.100410","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Asthma involves variable airflow limitation and persistent airway inflammation. Eosinophilic asthma, characterized by cytokine-mediated type 2 inflammation, is generally treated with inhaled corticosteroids. However, patients with severe asthma may require biologics, such as mepolizumab, which targets IL-5 and can manage uncontrolled eosinophilic asthma.</div></div><div><h3>Objective</h3><div>We investigated the relationship between serum mepolizumab concentrations and treatment response in patients with severe asthma.</div></div><div><h3>Methods</h3><div>Patients with mepolizumab-treated severe asthma were enrolled onto this prospective cohort study. Baseline assessments were conducted and repeated at 3, 6, and 12 months. Those with response were categorized on the basis of improvements in asthma control test score, lung function, and asthma exacerbations. We quantified the serum concentration of mepolizumab at 3, 6, and 12 months after treatment by liquid chromatography coupled with tandem mass spectrometry.</div></div><div><h3>Results</h3><div>Twenty-five adult patients aged 20 years and older with severe asthma were included in the analysis. Serum mepolizumab concentrations significantly increased at 6 and 12 months compared with those at 3 months, particularly in those with disease that responded to therapy. Furthermore, the relative change in mepolizumab concentration was significantly higher in those with response than in those with no response. Body size parameters were negatively correlated with mepolizumab concentration. In those with response, there were inverse correlations between mepolizumab concentration and baseline body size parameters.</div></div><div><h3>Conclusions</h3><div>The study observed a yearlong increase in mepolizumab concentrations, particularly in those with response, indicating a potential mepolizumab surplus. Correlations between mepolizumab concentrations and baseline characteristics suggested differing mepolizumab requirements between those with response and those with no response. Further research is needed to validate these findings and optimize treatment strategies for patients with severe asthma.</div></div>","PeriodicalId":75041,"journal":{"name":"The journal of allergy and clinical immunology. Global","volume":"4 2","pages":"Article 100410"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The journal of allergy and clinical immunology. Global","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772829325000116","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Asthma involves variable airflow limitation and persistent airway inflammation. Eosinophilic asthma, characterized by cytokine-mediated type 2 inflammation, is generally treated with inhaled corticosteroids. However, patients with severe asthma may require biologics, such as mepolizumab, which targets IL-5 and can manage uncontrolled eosinophilic asthma.

Objective

We investigated the relationship between serum mepolizumab concentrations and treatment response in patients with severe asthma.

Methods

Patients with mepolizumab-treated severe asthma were enrolled onto this prospective cohort study. Baseline assessments were conducted and repeated at 3, 6, and 12 months. Those with response were categorized on the basis of improvements in asthma control test score, lung function, and asthma exacerbations. We quantified the serum concentration of mepolizumab at 3, 6, and 12 months after treatment by liquid chromatography coupled with tandem mass spectrometry.

Results

Twenty-five adult patients aged 20 years and older with severe asthma were included in the analysis. Serum mepolizumab concentrations significantly increased at 6 and 12 months compared with those at 3 months, particularly in those with disease that responded to therapy. Furthermore, the relative change in mepolizumab concentration was significantly higher in those with response than in those with no response. Body size parameters were negatively correlated with mepolizumab concentration. In those with response, there were inverse correlations between mepolizumab concentration and baseline body size parameters.

Conclusions

The study observed a yearlong increase in mepolizumab concentrations, particularly in those with response, indicating a potential mepolizumab surplus. Correlations between mepolizumab concentrations and baseline characteristics suggested differing mepolizumab requirements between those with response and those with no response. Further research is needed to validate these findings and optimize treatment strategies for patients with severe asthma.
mepolizumab治疗对1年治疗有反应的严重哮喘患者mepolizumab水平升高
哮喘包括可变气流限制和持续气道炎症。嗜酸性粒细胞性哮喘,以细胞因子介导的2型炎症为特征,通常用吸入皮质类固醇治疗。然而,严重哮喘患者可能需要生物制剂,如mepolizumab,其靶向IL-5,可以控制不受控制的嗜酸性哮喘。目的探讨重症哮喘患者血清美polizumab浓度与治疗反应的关系。方法将mepolizumab治疗的重症哮喘患者纳入这项前瞻性队列研究。基线评估在3、6和12个月时进行并重复。根据哮喘控制测试分数、肺功能和哮喘恶化程度的改善对有反应的患者进行分类。我们在治疗后3、6和12个月用液相色谱联用串联质谱法定量了mepolizumab的血清浓度。结果本组共纳入25例20岁及以上成人重症哮喘患者。与3个月时相比,血清mepolizumab浓度在6个月和12个月时显著增加,特别是在那些对治疗有反应的疾病中。此外,mepolizumab浓度的相对变化在有反应的患者中显著高于无反应的患者。体型参数与mepolizumab浓度呈负相关。在有反应的患者中,美polizumab浓度与基线体型参数呈负相关。该研究观察到美polizumab浓度持续一年的增加,特别是在那些有反应的患者中,表明潜在的美polizumab过剩。mepolizumab浓度与基线特征之间的相关性表明,有反应和无反应的患者对mepolizumab的需求不同。需要进一步的研究来验证这些发现并优化严重哮喘患者的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
The journal of allergy and clinical immunology. Global
The journal of allergy and clinical immunology. Global Immunology, Allergology and Rheumatology
CiteScore
0.70
自引率
0.00%
发文量
0
审稿时长
92 days
×
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