偏头痛“神药”真有那么神么？-CGRP拮抗剂介绍

<p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">(本文发布于2021年，目前数据有所更新)</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">一、什么是CGRP？</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">（正式英文名：calcitonin gene-related peptide），中文名称：降钙素基因相关肽，它是一种在大脑神经系统周围释放的蛋白质，CGRP 广泛分布于中枢、外周和其他系统中。CGRP 的作用是参与神经系统中疼痛传递的过程，它会引起大脑脑膜的强烈炎症。科学家们发现在偏头痛发作期间科CGRP的水平会升高，如果你给偏头痛患者注射 CGRP，即么在 4 小时内，大部分患者都会出现偏头痛。CGRP拮抗剂的作用就是通过阻断 CGRP传递的方式来阻止偏头痛， 这就是所有CGRP拮抗剂的理论基础。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: center;"><span style="font-size: 18px;"><img src="/uploads/ueditor/20230505/b421e3364c29b1486b5757a61af8da33.jpg" title="b421e3364c29b1486b5757a61af8da33.jpg" alt="b421e3364c29b1486b5757a61af8da33.jpg"/></span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">二、CGRP拮抗剂的类型</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">目前共有两种类型的CGRP 拮抗剂 - 单克隆抗体和CGRP受体拮抗剂（名为Gepants）。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">（一）单克隆抗体。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">单克隆抗体的靶向点是CGRP或CGRP受体，主要用于偏头痛的预防。通俗讲，单克隆抗体是专门攻击特定蛋白质的一种人工合成的蛋白质的集合。为避免被胃液降解，它们通过皮下注射的方式用药，所以对肝脏或肾脏损伤可能性较小。单克隆抗体是大分子，所以在大脑里起效较慢。目前有四种获批：</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">1、Aimovig （erenumab-aooe）2018年5月17日批准</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">2、Ajovy（fremanezumab）2018年9月14日批准</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">3、Emgality （galcanezumab-gnlm）2018年9月27日批准</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">4、Vyepti（eptinezumab-jjmr）2020年2月21日批准。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">（二）CGRP受体拮抗剂（Gepants）</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">Gepants是阻断CGRP与CGRP受体结合的小分子药物，可以缓解偏头痛和预防偏头痛。与单克隆抗体不同，gepants能够迅速进入大脑，起效非常快。但经由肝脏代谢，引起肝损伤潜在风险较高。目前有三种获批：</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">1、Ubrelvy （ubrogepant）2019年12月23日批准</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">2、Nurtec ODT (rimegepant sulfate)2020年2月27日批准。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">3、Qulipta（atogepant）2021年9月28日批准</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">4、vazagepant(BHV-3500，Biohaven)三期临床中，2022年1月出结论</span></p><p style="margin-top: 0px; margin-bottom: 2px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;"><strong>三、目前备受瞩目的偏头痛“神药”CGRP拮抗剂，大部分已经完成了三期临床试验，这款被全球10亿患者寄以厚望的新药到底怎么样呢？</strong></span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">从结果看，CGRP抑制剂交上的这份答卷并没有达到预期中的“神药”级效果，但是综合评价其治疗、预防效果及其副作用，100分的话可以打70分吧。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">篇幅所限，这次介绍这款新药相比市面上其他偏头痛药物的优势与不足。</span></p><p style="margin-top: 0px; margin-bottom: 2px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;"><strong>（一）CGRP的优势</strong></span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">1、相比目前治疗偏头痛的主力曲坦类药物，CGRP拮抗剂对心血管疾病患者相对安全。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;"><strong>2、</strong>CGRP单抗具有分子量大，半衰期长（药效持续时间长）的特点，而小分子CGRP抑制剂则起效快，可用于偏头痛的急性救治。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;"><strong>3、</strong>有的偏头痛药物使用一段时间就会失去效果，而目前CGRP抑制剂还未发现失去治疗效果的现象。（时间太短，数据尚不完善）</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">4、用药方式多。皮下注射、静脉滴注、口服片剂、鼻喷雾剂。总有一款适合你。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;"><strong>5、&nbsp;</strong>服用频次每月只需服用一次到两次。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">6、副作用较小。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">常风副作用：恶心、便秘、消化不良、口干、鼻塞、疲倦、过敏反应、^{注射部位的发红，疼痛或肿胀}等。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">少见副作用：口干、嗜睡、荨麻疹、皮疹、皮肤发红、鼻子内部肿胀等。比起其他药物来，算是非常友好了。</span></p><p style="margin-top: 0px; margin-bottom: 2px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;"><strong>（二）CGRP的缺点</strong></span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">1、依然属于治标的范围，还不能根治偏头痛，也许是之前的期望太高，也许在将来第三代、或更新一代药物才能达到目的。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;Helvetica Neue&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;">2、根据临床试验，CGRP仍对一部分受试者无效（约40%左右）。依然不能算是一款偏头痛患者百试百爽的特效药。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;PingFang SC&quot;; white-space: normal; text-align: left;"><span style="font-size: 18px;"><span style="font-size: 18px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; line-height: normal; font-family: &quot;Helvetica Neue&quot;;">1</span>、太贵！<span style="font-size: 18px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; line-height: normal; font-family: &quot;Helvetica Neue&quot;;">CGRP</span>靶向药物治疗偏头痛的费用每年约为<span style="font-size: 18px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; line-height: normal; font-family: &quot;Helvetica Neue&quot;;">6000-7000</span>美元，即每月大约在<span style="font-size: 18px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; line-height: normal; font-family: &quot;Helvetica Neue&quot;;">500-600</span>美元之间。</span></p><p style="margin-top: 0px; margin-bottom: 0px; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-kerning: auto; font-optical-sizing: auto; font-feature-settings: normal; font-variation-settings: normal; font-stretch: normal; font-size: 13px; line-height: normal; font-family: &quot;PingFang SC&quot;; white-space: normal; text-align: center;"><span style="font-size: 18px;"><img src="/uploads/ueditor/20230505/8a062b61c1231d99a5f9e3b1c9fce8b1.jpg" title="8a062b61c1231d99a5f9e3b1c9fce8b1.jpg" alt="8a062b61c1231d99a5f9e3b1c9fce8b1.jpg"/></span></p><p style="text-align: center;"><br style="text-align: left;"/></p>