Why are CGRP monoclonal antibodies not yet the first line treatment in migraine prevention?

ABSTRACT Migraine is a prevalent disorder and a cause of high disability, influenced by modifiable and non-modifiable risk factors. Comorbid and psychiatric illnesses are prevalent in migraine patients and should be considered when choosing preventive drugs. There have been unforeseen problems with the use of preventive treatment of migraine with oral drugs, mainly due to side-effects that cannot be tolerated and lack of efficacy, leading to high discontinuation rates. Anti-CGRP monoclonal antibodies (mAbs) have shown better tolerance profiles, based on the low dropout rates in clinical trials due to adverse events. First-line therapy is a term most expressed in some medical specialties that adopt standardized protocol treatments and may not be suitable for treating migraine. Regarding efficacy, mAbs don’t seem to perform much better than the current prophylactic oral drugs in reduction of monthly migraine days compared to placebo. Monoclonal antibodies against CGRP pathway have been prescribed recently, which raises some concern about their safety in the long term. Only side effects observation will confirm whether CGRP blockade causes susceptibility to severe side-effects, at least to specific subpopulations. CGRP may play a role in regulating uteroplacental blood flow and myometrial and uterine relaxation, as well as blood pressure control, raising the suspicion that its blockade could cause complications during pregnancy. Recent guidelines retain the recommendation of starting preventive treatment of migraine with oral drugs. Both the fact that it is new and costs are the reason why guidelines recommend the prescription of mAbs only after failure of at least two oral drugs.

摘要：偏头痛是一种常见疾患，亦是导致高致残性的病因之一，其发病受可改变及不可改变的危险因素影响。偏头痛患者常合并共病与精神疾患，在选择预防性药物时需将此类情况纳入考量。偏头痛预防性口服药物治疗曾出现未预料到的问题，主要源于无法耐受的不良反应与疗效不足，进而导致较高的停药率。降钙素基因相关肽（CGRP）单克隆抗体（mAbs）展现出更优的耐受性特征，临床试验中因不良事件导致的脱落率较低。一线治疗是部分采用标准化诊疗方案的医学专科中常用的术语，但其或并不适用于偏头痛的治疗。就疗效而言，与安慰剂相比，此类单克隆抗体在减少每月偏头痛天数方面的表现并未显著优于当前主流的预防性口服药物。靶向CGRP通路的单克隆抗体近年来已投入临床使用，这引发了人们对其长期安全性的担忧。唯有通过不良反应监测，才能证实CGRP阻断是否会使特定亚群人群出现严重不良反应的易感性升高。CGRP或可参与调控子宫胎盘血流量、子宫肌层与子宫舒张功能以及血压稳态，据此有推测认为，阻断CGRP可能会引发妊娠期间的并发症。近期发布的指南仍保留了偏头痛预防性口服药物治疗的推荐意见。指南之所以仅推荐在至少两种口服药物治疗失败后使用此类单克隆抗体，其原因既包括其上市时间较短，也涉及治疗成本因素。