Achal Patel, Mercer University College of Pharmacy
It is reported that migraines are the third most prevalent illness in the world, prominently affecting women.  Symptoms include visual disturbances, extreme sensitivity to sound, light, touch, and smell, and tingling or numbness in the extremities and face.  Migraines can be classified as either episodic (< 15 headache days/month) or chronic (≤ 15 headache days/month). 
Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor that is involved in migraine pathophysiology through nociceptive mechanisms in the trigeminovascular system.  In a prior phase two trial, erenumab has shown a reduction in the number of episodic migraines at monthly doses of 70 mg and 140 mg. 
|A controlled trial of erenumab for episodic migraine|
|Design||Multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 trial; N= 955|
|Objective||To test erenumab for the prevention of episodic migraine|
|Study Groups||Erenumab 70 mg (n= 317), Erenumab 140 mg (n= 319), and Placebo (n= 319)|
|Methods||Patients were randomly assigned in a 1:1:1 ratio to receive monthly subcutaneous injections of 70 mg of erenumab, 140 mg of erenumab, or placebo at day 1 and weeks 4, 8, 12, 16, and 20
During baseline and double-blind treatment phases, patients completed an electronic diary daily with information about their migraine and non-migraine headaches, including the date and time of onset and resolution, pain severity and features, associated symptoms, and the use of migraine-specific abortive therapies and analgesic medications. Patients also completed the Migraine Physical Function Impact Diary (MPFID), a 13-item self-administered tool that measures physical functioning in the past 24 hours, on migraine and non-migraine days using the electronic diary.
– Adults 18 to 65 years of age
– History of migraine with or without aura for at least 12 months before screening
– Patients had to have at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the 3-month period before screening
– During a 4-week baseline phase that was assessed with the use of a handheld electronic diary (ERT) completed daily by the patient and had to demonstrate at least 80% adherence to reporting with the electronic diary during the baseline phase
– Patients were excluded if they had no therapeutic response in migraine prevention after an adequate therapeutic trial of >2 of the following medication categories:
o Category 1: Divalproex sodium, sodium valproate
o Category 2: Topiramate
o Category 3: Beta blockers
o Category 4: Tricyclic antidepressants
o Category 5: Serotonin-norepinephrine reuptake inhibitors
o Category 6: Flunarizine, verapamil
o Category 7: Lisinopril, candesartan
– The following medications, devices, or procedures were excluded:
o Botulinum toxin
o Ergotamine derivatives, steroids, and triptans
o Devices and procedures used for migraine prophylaxis
o Investigational medications and devices
o Patients also must not have used investigational medications or devices for at least 90 days prior to screening
|Duration||July 2015 – September 2016|
|Primary Outcome Measure||Change from baseline to four months through six in the mean number of migraine days per month|
|Study Author Conclusions||Erenumab significantly reduced migraine frequency, effects of migraine on daily activities, and the use of acute migraine-specific medication over a six-month period.|
Although erenumab demonstrated efficacy in the study, baseline suggests patients had mild migraine and >50% of patients have never used preventative medications. Moreover, it shows a small number of patients failed previous treatment due to lack of efficacy. Together, it is reasonable to question whether these patients may have also responded to other currently recommended first-line treatments (i.e. beta-blockers, triptans, and antiepileptic drugs). In addition, despite being monthly injection, it is expected that the cost of erenumab may be high similar to other drugs in the same class (monoclonal antibodies). Considering these limitations, even if the drug is approved, its use may be limited to mild migraines, and without other significant benefits (e.g. improved quality of life), it may be considered a second-line therapy.
 Migraine facts. Migraine research foundation. http://migraineresearchfoundation.org/about-migraine/migraine-facts/. Accessed January 25, 2018.
 Headache classification committee of the international headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33:629-808
 Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123-2132.
 Silberstein SD, Holland S, Freitag F. et. al. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults. American Headache Society.