降钙素基因相关肽（CGRP）和血管活性肠肽（VIP）水平作为A型肉毒毒素治疗慢性偏头痛疗效的预测指标

CGRP and VIP levels as predictors of efficacy of Onabotulinumtoxin type A in chronic migraine.

作者信息

Cernuda-Morollón Eva, Martínez-Camblor Pablo, Ramón César, Larrosa Davinia, Serrano-Pertierra Esther, Pascual Julio

机构信息

Neuroscience Area, Service of Neurology, University Hospital Central de Asturias and Ineuropa, Oviedo, Spain.

出版信息

Headache. 2014 Jun;54(6):987-95. doi: 10.1111/head.12372. Epub 2014 May 6.

DOI:10.1111/head.12372

PMID:24673487

Abstract

BACKGROUND

Onabotulinumtoxin type A (onabotA) has shown efficacy in chronic migraine (CM). Its precise mechanism of action, however, is unknown.

OBJECTIVE

To analyze a potential relationship between calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) levels and response to onabotA in CM.

METHODS

Adult patients with CM were recruited. Matched healthy subjects with no headache history served as controls. CGRP and VIP levels were determined in samples obtained from the right antecubital vein by ELISA outside of a migraine attack and having taken no symptomatic medication prior to treatment with onabotA. OnabotA was administered according to the PREEMPT protocol every 12 weeks for at least two treatment cycles. A patient was considered as a moderate responder when both: (1) moderate-severe headache episodes were reduced by between 33 and 66%; (2) subjective benefit in a visual scale of 0-100 was recorded by the patient of between 33-66%. Patients were considered as excellent responders when both items improved >66%. Those without improvement of at least one-third in the two items were considered as nonresponders.

RESULTS

We assessed plasma samples from 81 patients with CM and 33 healthy controls. CGRP and VIP levels were significantly increased in CM population vs controls. CGRP and, to a lesser degree, VIP levels were significantly increased in responders vs nonresponders. For CGRP, a threshold of 72 pg/mL positively correlated with 95% of nonresponders. The probability of being a responder to onabotA was 28 times higher in patients with a CGRP level above the threshold of 72 pg/mL. Even though the sensitivity for the calculated threshold for VIP was poor, the probability that CM patients with low CGRP levels will respond to onabotA was significantly higher in those patients with high VIP levels.

CONCLUSIONS

Interictal CGRP and, to a lesser degree, VIP levels measured in peripheral blood are of great help in predicting response to onabotA.

摘要

背景

A型肉毒毒素（onabotA）已显示出对慢性偏头痛（CM）有效。然而，其确切作用机制尚不清楚。

目的

分析降钙素基因相关肽（CGRP）和血管活性肠肽（VIP）水平与CM患者对onabotA反应之间的潜在关系。

方法

招募成年CM患者。匹配无头痛病史的健康受试者作为对照。在偏头痛发作之外且在接受onabotA治疗前未服用对症药物的情况下，通过酶联免疫吸附测定法（ELISA）从右肘前静脉采集的样本中测定CGRP和VIP水平。按照PREEMPT方案每12周给予onabotA，至少进行两个治疗周期。当以下两个条件同时满足时，患者被视为中度反应者：（1）中重度头痛发作减少33%至66%；（2）患者在0至100的视觉量表上记录的主观获益为33%至66%。当两项指标改善均>66%时，患者被视为优秀反应者。两项指标中至少有一项未改善至少三分之一的患者被视为无反应者。

结果

我们评估了81例CM患者和33例健康对照的血浆样本。与对照组相比，CM患者群体中CGRP和VIP水平显著升高。与无反应者相比，反应者的CGRP以及程度较轻的VIP水平显著升高。对于CGRP，72 pg/mL的阈值与95%的无反应者呈正相关。CGRP水平高于72 pg/mL阈值的患者对onabotA有反应的概率高出28倍。尽管计算出的VIP阈值敏感性较差，但低CGRP水平的CM患者中，高VIP水平患者对onabotA有反应的概率显著更高。