在发作性和慢性偏头痛患者中使用 fremanezumab 的安全性和耐受性：3 期研究的汇总分析。
Safety and tolerability of fremanezumab in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies.
机构信息
Institute for Medical Informatics, Biometry, and Epidemiology, Medical Faculty of the University Duisburg-Essen, Essen, Germany.
New England Institute for Neurology and Headache, Stamford, CT, USA.
出版信息
Cephalalgia. 2022 Jul;42(8):769-780. doi: 10.1177/03331024221076485. Epub 2022 Mar 25.
BACKGROUND
Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, has demonstrated efficacy for preventive treatment of episodic and chronic migraine. Since calcitonin gene-related peptide is expressed within the cardio- and cerebrovascular system and may have cardioprotective effects, it is critical to understand the cardio- and cerebrovascular safety of fremanezumab.
METHODS
This was a pooled analysis of three randomized, double-blind, placebo-controlled, phase 3, 12-week trials in which patients with episodic migraine or chronic migraine received quarterly fremanezumab, monthly fremanezumab, or placebo. Incidences of overall and serious adverse events were analyzed. Cardio- and cerebrovascular adverse events (CVAEs) were analyzed in subgroups stratified by cardio- and cerebrovascular medical history, cardiovascular risk factors (CVRFs), and use of cardio- and cerebrovascular medications or triptans.
RESULTS
Two thousand, eight hundred and forty-two patients were included in the study. Overall (58-65%) and serious adverse events (<1-2%) occurred in similar proportions across fremanezumab and placebo groups. CVAEs were infrequent, regardless of cardio- and cerebrovascular medical history (2-6%). CVAEs occurred in low, similar proportions of patients with CVRFs and those using cardio- and cerebrovascular medications or triptans. No cardio- and cerebrovascular signals were identified.
CONCLUSION
Fremanezumab demonstrated a favorable overall and cardio- and cerebrovascular safety profile in more than 2800 patients with episodic migraine or chronic migraine, regardless of cardio- and cerebrovascular medical history, CVRFs, or medication use. NCT02629861 (HALO EM, https://clinicaltrials.gov/ct2/show/NCT02629861), NCT02621931 (HALO CM, https://clinicaltrials.gov/ct2/show/NCT02621931), NCT03308968 (FOCUS, https://clinicaltrials.gov/ct2/ show/NCT03308968).
背景
降钙素基因相关肽是一种选择性靶向降钙素基因相关肽的全人源化单克隆抗体，已被证明对发作性和慢性偏头痛的预防性治疗有效。由于降钙素基因相关肽在心血管系统中表达，并可能具有心脏保护作用，因此了解降钙素基因相关肽对心血管系统的安全性至关重要。
方法
这是一项对三项随机、双盲、安慰剂对照、3 期、12 周试验的汇总分析，其中患有发作性偏头痛或慢性偏头痛的患者接受了每季度一次的降钙素基因相关肽、每月一次的降钙素基因相关肽或安慰剂治疗。分析了总不良事件和严重不良事件的发生率。根据心血管病史、心血管危险因素（CVRFs）、以及心血管和/或脑血管药物或曲坦类药物的使用情况，对心血管不良事件（CVAEs）进行了亚组分析。
结果
共有 2842 名患者纳入研究。降钙素基因相关肽组和安慰剂组的总不良事件（58-65%）和严重不良事件（<1-2%）发生率相似。无论是否有心血管病史（2-6%），CVAEs 均不常见。在有 CVRFs 和使用心血管和/或脑血管药物或曲坦类药物的患者中，CVAEs 的发生率较低且相似。未发现心血管信号。
结论
在 2800 多名患有发作性偏头痛或慢性偏头痛的患者中，降钙素基因相关肽显示出良好的总体和心血管安全性特征，无论其是否有心血管病史、CVRFs 或用药情况如何。NCT02629861（HALO EM，https://clinicaltrials.gov/ct2/show/NCT02629861），NCT02621931（HALO CM，https://clinicaltrials.gov/ct2/show/NCT02621931），NCT03308968（FOCUS，https://clinicaltrials.gov/ct2/show/NCT03308968）。
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