Therapies for Migraine Prophylaxis

June 8, 2018

Mode of delivery, mechanism of action, and efficacy of a novel treatment are discussed in this research update.

RESEARCH UPDATE

A number of medications are already used off label for migraine prophylaxis. These include anticonvulsants, antidepressants, and NSAIDs. But Aimovig (erenumab) is the first medication to be formally granted the indication of migraine prevention by the FDA.

Mode of delivery

Unlike other migraine medications that are typically daily oral pills, Aimovig is taken as a monthly injection. It is self-administered using Amgen’s device, an autoinjector that delivers a one-time 70 mg. dose. It is recommended to be taken once a month for migraine prophylaxis.

Mechanism of action

Aimovig is very different from other medications prescribed for either migraine prophylaxis or for treatment of acute migraine attacks. It is a monoclonal antibody, which is a type of molecule that is more often used for cancer treatment.

The mechanism of action of this particular monoclonal antibody is to block the calcitonin gene-related peptide (CGRP) receptor. Several medications with a similar mechanism of action are in the pipeline. Eptinezumab, fremanezumab, and galcanezumab are monoclonal antibodies that act against CGRP, while erenumab targets the CGRP receptor.

The amount of CGRP may increase in the circulation during migraine attacks. CGRP is a peptide that works as a vasodilator and well as a pain-signaling molecule. So the medication would be expected to induce vasoconstriction or prevent vasodilation, and to play a role in modulating pain.

Adverse effects

Pain, redness, or swelling at the injection site and constipation have been reported. Authors of a recent article in Neurotherapeutics point out that “the potential risk of vascular adverse events and the role of anti-drug antibodies,” of this class of medication should be considered.1

Efficacy

A 2017 article in the New England Journal of Medicine reported the results of a study of 955 patients with migraine.2 Of the study group, 317 participants received 70mg of erenumab administered subcutaneously; 319 received 140 mg of erenumab administered subcutaneously; and 319 received placebo.

The authors report that both the 70 mg and the 140 mg erenumab groups experienced significantly reduced migraine frequency, fewer effects of their migraines on their daily activities, and used less acute migraine-specific medication over a period of 6 months.A number of other randomized placebo controlled trials showed similarly positive results.

How will CGRP blockers change migraine prevention?

At this point, it may be too soon to know how much Aimovig will change the lives of patients who suffer from recurrent migraine headaches. Some patients who are happy with their current medication will not switch, and those who have infrequent migraines might not opt for prophylaxis at all. But there is a significant portion of migraine sufferers who experience too many migraines despite other prophylaxis or who do not get adequate migraine control from treatments that are currently available for acute migraines.

In the coming years, patients’ experiences in terms of migraine frequency and severity, as well as adverse effects, will be interesting for neurologists as we learn more about the practical aspects of Aimovig and other anti-CGRP medications.

Watch the video: New Hope for Migraine Patients

References:

1. Raffaelli B, Reuter U. The Biology of Monoclonal Antibodies: Focus on Calcitonin Gene-Related Peptide for Prophylactic Migraine Therapy. Neurotherapeutics. 2018;15:324-335.

2. Goadsby PJ, Reuter U, Hallström Y, et al. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017;377:2123-2132.