Serum Neurofilament Light Chain in Multiple Sclerosis: Superiority of Age- and BMI-Corrected Z Scores/Percentiles Over Absolute Cutoff Values for Prediction of Treatment Response.

IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY
Maximilian Einsiedler, Aleksandra Maleska Maceski, Sofia Sandgren, Johanna Oechtering, Sabine Schaedelin, Lisa Hofer, Amar Zadic, Juan Francisco Vilchez Gomez, Lester Melie-Garcia, Alessandro Cagol, Riccardo Galbusera, Sebastian Finkener, Patrice Lalive, Marjolaine Uginet, Stefanie Müller, Caroline Pot, Amandine Mathias, Renaud Du Pasquier, Robert Hoepner, Andrew Chan, Giulio Disanto, Chiara Zecca, Marcus D'Souza, Lars G Hemkens, Tobias Derfuss, Özgür Yaldizli, Patrick Roth, Claudio Gobbi, David Brassat, Björn Tackenberg, Henrik Zetterberg, Tjalf Ziemssen, Heinz Wiendl, Klaus Berger, Marco Hermesdorf, Fredrik Piehl, Ludwig Kappos, Cristina Granziera, Ahmed Abdelhak, David Leppert, Eline A J Willemse, Pascal Benkert, Jens Kuhle
{"title":"Serum Neurofilament Light Chain in Multiple Sclerosis: Superiority of Age- and BMI-Corrected Z Scores/Percentiles Over Absolute Cutoff Values for Prediction of Treatment Response.","authors":"Maximilian Einsiedler, Aleksandra Maleska Maceski, Sofia Sandgren, Johanna Oechtering, Sabine Schaedelin, Lisa Hofer, Amar Zadic, Juan Francisco Vilchez Gomez, Lester Melie-Garcia, Alessandro Cagol, Riccardo Galbusera, Sebastian Finkener, Patrice Lalive, Marjolaine Uginet, Stefanie Müller, Caroline Pot, Amandine Mathias, Renaud Du Pasquier, Robert Hoepner, Andrew Chan, Giulio Disanto, Chiara Zecca, Marcus D'Souza, Lars G Hemkens, Tobias Derfuss, Özgür Yaldizli, Patrick Roth, Claudio Gobbi, David Brassat, Björn Tackenberg, Henrik Zetterberg, Tjalf Ziemssen, Heinz Wiendl, Klaus Berger, Marco Hermesdorf, Fredrik Piehl, Ludwig Kappos, Cristina Granziera, Ahmed Abdelhak, David Leppert, Eline A J Willemse, Pascal Benkert, Jens Kuhle","doi":"10.1002/acn3.70149","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Prognostication of disease course and prediction of treatment response in multiple sclerosis is an unmet need. We compared the performance of serum neurofilament light chain Z scores (age- and BMI-adjusted) with absolute concentrations for the prediction of response to disease-modifying therapy.</p><p><strong>Methods: </strong>Observational cohort study including the first serum sample of participants after the start of fingolimod therapy. We estimated hazard ratios for future relapses comparing participants with high (upper quartile) versus lower neurofilament light chain levels, based on either absolute concentration or Z score cutoffs. We compared the prognostic/predictive performance of these two measures for the occurrence of new/enlarging T2w lesions in longitudinal MRI.</p><p><strong>Results: </strong>We included 447 participants (median [IQR] age, 41.3 [32.1-49.2] years; 65.1% female); median follow-up 8.3 years [6.0-10.3]. Participants with a high neurofilament light chain Z score (Z ≥ 1.2/88.5 percentile) were more likely to experience future relapses (HR: 1.80, 95% CI 1.27-2.54, p < 0.001) compared to those below this threshold while this dichotomy could not be demonstrated with absolute concentration cutoffs (≥ vs. < 10.8 pg/mL; HR: 0.94, 95% CI 0.64-1.38, p = 0.75). Furthermore, patients with upper quartile Z scores were associated with a higher incidence of new/enlarging T2w lesions compared with those below this threshold (OR: 1.88, 95% CI 1.31-2.70, p < 0.001); again, absolute concentration cutoffs failed to identify this risk (OR: 1.20, 95% CI 0.82-1.77, p = 0.34). These findings were confirmed when patients having started alternative oral treatments were also included (n = 713).</p><p><strong>Interpretation: </strong>Serum neurofilament light chain Z scores consistently outperformed absolute concentration cutoffs for prognostication of clinical/radiological disease activity and may facilitate individual prediction of treatment response.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Clinical and Translational Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/acn3.70149","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: Prognostication of disease course and prediction of treatment response in multiple sclerosis is an unmet need. We compared the performance of serum neurofilament light chain Z scores (age- and BMI-adjusted) with absolute concentrations for the prediction of response to disease-modifying therapy.

Methods: Observational cohort study including the first serum sample of participants after the start of fingolimod therapy. We estimated hazard ratios for future relapses comparing participants with high (upper quartile) versus lower neurofilament light chain levels, based on either absolute concentration or Z score cutoffs. We compared the prognostic/predictive performance of these two measures for the occurrence of new/enlarging T2w lesions in longitudinal MRI.

Results: We included 447 participants (median [IQR] age, 41.3 [32.1-49.2] years; 65.1% female); median follow-up 8.3 years [6.0-10.3]. Participants with a high neurofilament light chain Z score (Z ≥ 1.2/88.5 percentile) were more likely to experience future relapses (HR: 1.80, 95% CI 1.27-2.54, p < 0.001) compared to those below this threshold while this dichotomy could not be demonstrated with absolute concentration cutoffs (≥ vs. < 10.8 pg/mL; HR: 0.94, 95% CI 0.64-1.38, p = 0.75). Furthermore, patients with upper quartile Z scores were associated with a higher incidence of new/enlarging T2w lesions compared with those below this threshold (OR: 1.88, 95% CI 1.31-2.70, p < 0.001); again, absolute concentration cutoffs failed to identify this risk (OR: 1.20, 95% CI 0.82-1.77, p = 0.34). These findings were confirmed when patients having started alternative oral treatments were also included (n = 713).

Interpretation: Serum neurofilament light chain Z scores consistently outperformed absolute concentration cutoffs for prognostication of clinical/radiological disease activity and may facilitate individual prediction of treatment response.

多发性硬化症血清神经丝轻链:年龄和bmi校正Z分数/百分位数在预测治疗反应的绝对临界值上的优势
目的:预测多发性硬化症的病程和治疗反应是一个尚未满足的需求。我们比较了血清神经丝轻链Z评分(年龄和bmi调整)与绝对浓度的表现,以预测对疾病改善治疗的反应。方法:观察性队列研究,包括参与者开始芬戈莫治疗后的第一次血清样本。我们根据绝对浓度或Z评分临界值,比较高(上四分位数)和低神经丝轻链水平的参与者,估计未来复发的风险比。我们比较了这两种方法在纵向MRI中对新发/扩大T2w病变的预后/预测性能。结果:我们纳入了447名参与者(中位[IQR]年龄为41.3[32.1-49.2]岁;65.1%女性);中位随访时间8.3年[6.0-10.3]。高神经丝轻链Z评分(Z≥1.2/88.5百分位)的参与者更有可能经历未来的复发(HR: 1.80, 95% CI 1.27-2.54, p)解释:血清神经丝轻链Z评分始终优于临床/放射学疾病活动性预测的绝对浓度临界值,并可能有助于个体预测治疗反应。
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
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
×
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:604180095
Book学术官方微信