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Migraine is a disabling, chronic neurologic disorder that affects more than 1 billion people worldwide.1,2 The 2016 Global Burden of Disease report revealed that migraine is the second most disabling condition worldwide, exceeded only by low back pain.2 In the United States, the Centers for Disease Control and Prevention report that 20% of women and 9.7% of men aged ≥18 years have had a severe headache or migraine in the past 3 months.3 Chronic migraine (CM) and episodic migraine (EM) negatively affect the quality of life of approximately 1 in 6 individuals in the United States,4 and migraine ranks as the number one cause of years lived with disability within the 15- to 49-year-old age group.5  

The International Headache Society has established criteria for the classification of CM and EM.6 Diagnostic criteria for CM includes headache on ≥15 days per month for more than 3 months, which on at least 8 days per month, has the features of migraines:  

  1. Migraine without aura
  2. Migraine with aura
  3. Believed by the patient to be migraine at onset and relieved by a triptan or ergot derivative

EM is defined as headache occurring on <15 days per month.6

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Individuals with migraine headaches use opioids twice as often as those without migraines.7 Migraine headaches place a significant burden on already vulnerable populations such as the unemployed, uninsured or underinsured, lower income individuals and families, the elderly, and the disabled, suggesting a serious public health concern that requires improvement.4 Indirect and direct healthcare costs for patients with migraine are significantly higher — on average $8924 more annually — than those for migraine-free individuals.8

Traditional Preventive Therapies

Undertreatment of migraine represents a great challenge; an estimated 66% of candidates for prophylactic migraine intervention go untreated.9,10 Several preventive treatments for frequent CM or EM — including divalproex sodium, topiramate, gabapentin, propranolol, and similar agents with antihypertensive, antidepressant, or antiepileptic actions — have been used for decades.11-13 These agents, however, have not been found to be uniformly efficacious. In a study of 1165 patients living with migraine, only 13.9% of patients on antidepressants (n=205), 11.2% on antiepileptics (n=125), and 11.5% on beta-blockers (n=130) said they found satisfactory resolution of their migraines through pharmacologic intervention.14 Nearly 50% of the patients discontinued their migraine therapy due to lack of efficacy or the side effects associated with treatment.14

In 2010, the US Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox® ) for the prevention of migraines.15,16 This alternative treatment avoids the unpleasant adverse effects that traditionally deter patient adherence to standard pharmacologic treatments including nausea, vomiting, somnolence, dizziness, paresthesia, memory impairment, appetite loss, and taste abnormalities.15

New, rationally designed migraine prophylaxis has been pursued since the 1990s. The calcitonin gene-related peptide (CGRP) pathway plays a significant role in the pain and other symptoms associated with the development of migraine headache.17 Trigeminal nerve dysfunction and hypersensitive sensory pathways contribute to the development of migraine.17 Researchers have progressed toward further understanding of both CM and EM headaches as well as their relationship with the CGRP pathway.18 

Review of Anti-CGRP Therapies

Anti-CGRP monoclonal antibodies (anti-CGRP mAbs) are the first approved pharmacologic treatments developed explicitly for the prevention of migraine.18-20 Since 2018, the FDA has approved 4 new preventive therapies to treat migraine: erenumab (Aimovig®), fremanezumab (Ajovy®), galcanezumab (Emgality®), and eptinezumab (Vyepti™ ) (Table 1).21-24

The FDA approved these new agents globally for migraine, whether CM or EM, as significant benefit and safety were documented in both CM and EM treatment trials.  The adult migraine indication shows that the FDA supports a wide spectrum of anti-CGRP utility in these populations. One agent also achieved approval for cluster headache.23

Approval of these agents validates the improved understanding and awareness of the underlying causes of migraine and presents a new opportunity for further education and better management of migraine as a chronic neurologic condition.