Shawn Yee, Mercer University College of Pharmacy
Migraine is a common neurological disorder that is ranked top 10 in terms of global disease burden.  The term migraine can be categorized into either episodic (< 15 migraine or headache days per month) or chronic (≥ 15 headache days per month, with ≥ eight days of migraine days).  Patients with debilitating or frequent migraines are eligible for preventative treatment; however, none of these options target the pathophysiologic pathways involved in migraines. 
Erenumab is a fully human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor, which is involved in migraine pathophysiology of the trigeminovascular system.  There are other monoclonal antibodies targeting CGRP, such as fremanezumb that have shown safety and efficacy in migraine prevention. Erenumab in particular, has also demonstrated efficacy in reducing the number of migraine days per month at doses ranging from 70 mg to 140 mg per month in a prior phase II trial. [3,4] Below is the summary of a phase III trial. 
|A controlled trial of erenumab for episodic migraine|
|Design||Multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase III trial; N= 955|
|Objective||Analyze if erenumab is effective for the prevention of episodic migraines|
|Methods||The trial had a screening phase (≤ three weeks), a baseline phase (four weeks), a double-blind treatment phase (24 weeks), an active-treatment phase with 70 mg or 140 mg of erenumab (28 weeks), and follow-up phase for safety (12 weeks). A total of 955 patients were randomized to receive subcutaneous injections of erenumab 70 mg/month, erenumab 140 mg/month, or placebo during the double-blind treatment phase. A Migraine Physical Function Impact Diary (MPFID) was used to assess the overall effect and burden of migraine, which scores up to 100, and higher scores indicate increased patient burden on functioning.
|Duration||July 2015 to September 2016|
|Primary Outcome Measure||Change in the average number of migraine days per month from baseline during months four through six|
|Adverse Events||Common Adverse Events: Not disclosed|
|Percentage that Discontinued due to Adverse Events: Less than 3% discontinued erenumab|
|Study Author Conclusions||Monthly doses of erenumab 70 mg SQ or 140 mg SQ significantly reduced migraine frequency, reduced the use of acute migraine medications, and improved quality of daily activities for patients.|
This study affirms the findings of erenumab’s efficacy from the previous phase II trial, which also tested the same dosage regimens of 70 mg or 140 mg subcutaneously every month. The results of this phase III trial indicate that both doses of erenumab may be effective in reducing migraine frequency, reducing acute migraine medications, and improving overall quality of life for patients. In the future, studies comparing the different doses directly may provide more insight into the dose effects of erenumab. The safety data for this study is also promising, with fewer than 3% of patients discontinuing erenumab and similar number of serious adverse events in comparison to placebo. However, long-term safety and efficacy still needs to be evaluated.
Based on the results, erenumab may be a treatment option to consider in patients with severe migraine attacks or patients who are refractory to other preventative treatments. To note, this study only included patients diagnosed with episodic migraines (< 15 migraine or headache days per month), and erenumab efficacy in chronic migraine patients remains to be seen. With erenumab monthly injection formulation, patient preference and adherence will have to be addressed as well as the cost associated with erenumab treatment.
 Hershey, AD. CGRP-the next frontier for migraine. N Engl J Med 2017; 377:2190-2191.
 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;377:2123-2132.
 Sun H, Dodick DW, Silberstein S, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15:382-390.