降钙素基因相关肽和 P 物质作为肉毒毒素 A 治疗慢性偏头痛疗效的预测因子：一项观察性研究。

CGRP and PTX3 as Predictors of Efficacy of Onabotulinumtoxin Type A in Chronic Migraine: An Observational Study.

机构信息

Department of Neurology, Hospital Clínico Universitario, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.

Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.

出版信息

Headache. 2018 Jan;58(1):78-87. doi: 10.1111/head.13211. Epub 2017 Nov 13.

DOI:10.1111/head.13211

PMID:29131327

Abstract

OBJECTIVE

The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA).

BACKGROUND

OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome.

METHODS

We measured serum levels of biomarkers of inflammation (IL-6, IL-10, TNF-α, and hs-CRP), endothelial dysfunction (PTX3 and sTWEAK), blood-brain barrier disruption (cFN), brain damage (S100b, NSE), and trigemino-vascular activation (CGRP) by ELISA in a group of CM patients treated with OnabotA and healthy controls. After 24 weeks, patients were classified in two groups according to their outcome considering variations in headache frequency: nonresponders (nonimprovement or improvement <50%) and responders (improvement >50%). We compared baseline levels of biomarkers between these groups.

RESULTS

Sixty-two patients diagnosed with CM (IHS 2013 criteria) who fulfilled criteria for treatment with OnabotA and 24 healthy controls were included. Fifteen patients did not respond to treatment (24.2%) and 47 were responders (75.8%). Pentraxin 3 (PTX3) serum levels (1455.4 ± 487.5 pg/mL versus 720.3 ± 334.1 pg/mL, P < .0001) and calcitonin gene-related peptide (CGRP) serum levels (133.1 ± 86.6 ng/mL versus 58.2 ± 91.7 ng/mL, P = .004) were significantly higher in responders than nonresponders. Serum basal levels of PTX3 >1000 pg/mL (AUC 0.908; 95% CI: 0.827-0.990) and CGRP >50 ng/mL (AUC 0.800; 95% CI: 0.652-0.947) were associated with good response to OnabotA treatment.

CONCLUSIONS

These results show that molecular markers of trigeminovascular activation (CGRP) and endothelial dysfunction (PTX3) are associated with response to OnabotA and may act as new biomarkers for the selection of treatment in chronic migraineurs.

摘要

目的

本研究旨在探讨外周血中几种生物标志物与接受肉毒毒素 A 治疗后的结局之间的关系。

背景

肉毒毒素 A 是慢性偏头痛（CM）的有效治疗方法。不同的研究试图通过临床特征、神经影像学特征或分子生物标志物来寻找治疗反应的预测因子；然而，仍然无法预测个体的结局。

方法

我们通过 ELISA 测量了一组接受肉毒毒素 A 治疗的 CM 患者和健康对照组的炎症（IL-6、IL-10、TNF-α 和 hs-CRP）、内皮功能障碍（PTX3 和 sTWEAK）、血脑屏障破坏（cFN）、脑损伤（S100b、NSE）和三叉神经血管激活（CGRP）的血清生物标志物水平。24 周后，根据头痛频率的变化将患者分为两组：无反应者（无改善或改善<50%）和反应者（改善>50%）。我们比较了这些组之间的生物标志物基线水平。

结果

共纳入 62 例符合肉毒毒素 A 治疗标准的 CM 患者（IHS 2013 标准）和 24 名健康对照组。15 例患者对治疗无反应（24.2%），47 例为反应者（75.8%）。反应者的血清 pentraxin 3（PTX3）水平（1455.4±487.5 pg/mL 与 720.3±334.1 pg/mL，P<0.0001）和降钙素基因相关肽（CGRP）水平（133.1±86.6 ng/mL 与 58.2±91.7 ng/mL，P=0.004）明显高于无反应者。PTX3 血清基础水平>1000 pg/mL（AUC 0.908；95%CI：0.827-0.990）和 CGRP>50 ng/mL（AUC 0.800；95%CI：0.652-0.947）与对肉毒毒素 A 治疗的良好反应相关。