The first calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) has received FDA approval and is now available for providers to prescribe. Why should primary care providers consider this novel category of preventive migraine medication for their patients? Which migraine patients are appropriate candidates for a CGRP mAb?
About 40% of migraine sufferers are candidates for prevention but only a small percentage are on a preventive.1 Lack of efficacy and intolerable side effects are among the top reasons for discontinuation of a preventive treatment.2 Even those medications that have an FDA indication for prevention of episodic or chronic migraine were not originally brought to market for migraine. These include topiramate, divalproex, propanolol, timolol, and onabotulinum toxin A.
CGRP, identified as a key player in the pathogenesis of migraine, is a neuropeptide that modulates nociceptive signaling. This signaling occurs through the trigeminal pathway. Activation of this pathway is associated with migraine pathophysiology.
Plasma levels of CGRP sampled from external jugular blood were reported to be higher in migraine patients actively experiencing a headache vs healthy control subjects.3 A follow-up study showed that elevated CGRP levels in external jugular blood returned to baseline following triptan administration.4 In addition, a study in which researchers infused CGRP or a placebo in migraine patients showed the development of headache in all patients receiving CGRP. Significantly, intravenous injections of CGRP did not trigger migraine-like attacks in healthy volunteers.5,6 The exact reason for this difference in susceptibility is unclear.
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1. Shapiro RE. Preventive treatment of migraine. Headache. 2012;52:65-69.
2. Blumenfeld AM, Bloudek LM, Becker WJ, et al. Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMS-II). Headache. 2013;53:644-655.
3. Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28:183-187.
4. Juhasz G, Zsombok T, Jakab B, et al. Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalalgia. 2005;25:179-183.
5. Lassen LH, Haderslev PA, Jacobsen VB, et al. CGRP may play a causative role in migraine. Cephalalgia. 2002;22:54-61.
6. Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010;30:1179-1186.
7. Aimovig [package insert]. Thousand Oaks, CA: Amgen Inc; 2018