The Role of Erenumab (Aimovig) in Treating Episodic, Chronic Migraines

The activation of sensory nerves in the trigeminovascular system leads to the release of neuropeptides, such as calcitonin gene-related peptide (CGRP), neurokinin A, and substance P. These neuropeptides stimulate vasodilation and plasma extravasation, causing neurogenic inflammation. Neurogenic inflammation is the underlying reason for the unilateral, pulsating, throbbing pain felt in migraine headaches.¹

Depending on headache severity and degree of disability, patients who suffer more than 2 severe headaches a month or 3-5 headaches a month with lower severity should be considered for prophylactic therapy.² Clinicians also ought to consider patients who have medication overuse headaches, which are headaches that occur 15 or more times per month in a patient who takes medications for 10 or more days per month consistently for more than 3 months.²

Prior to the discovery of anti-CGRP agents, prophylactic medications against migraines were drugs not specifically developed to prevent migraines but found to be efficacious after use for other indications. The American Headache Society (AHS) recommends topiramate, valproate, metoprolol, propranolol, or timolol for prophylaxis against migraines. Anti-CGRP agents are medications designed with the intention to treat migraines.²

Erenumab (Aimovig) was the first anti-CGRP agent approved by the FDA in May 2018. Erenumab is a monthly subcutaneous injection indicated for migraine prophylaxis. It is a human monoclonal antibody that binds to the CGRP receptor and antagonizes its action.

Its approval was based on trials where it demonstrated significant reduction in migraine days per month and use of acute migraine medications. It also decreased the degree of disability suffered by patients compared with placebo while increasing everyday activities in episodic migraines.^3-6 Furthermore, erenumab reduced monthly migraine days in patients with chronic migraines.^7,8

The impact was sustained at 52 weeks and 5 years, as well.^10,11

Post-hoc analyses of the studies illustrate onset of migraine prevention 1 week after administration of the first erenumab injection and improved patient-reported outcomes.^8,16 The 3 main trials studying erenumab were the STRIVE, ARISE, and LIBERTY trials.^3,4,18

The STRIVE trial showed that erenumab decreased monthly migraine occurrence by 3.7 days vs 1.8 for placebo (p<0.001). Fifty percent of the patients in the erenumab group had their migraine frequency decrease by half compared with only 27% in the placebo group (p<0.001).

Physical impairment score increased 4.8 points in erenumab group vs 2.4 in placebo group (p<0.001).³ The safety profile for erenumab is benign with constipation, nasopharyngitis, injection site pain, and possible hypertension as the main observed adverse effects (AEs).^3,4,18

The ARISE study demonstrated that erenumab lessened monthly migraines by 2.9 days vs 1.8 for the placebo group (p<0.001). Forty percent of patients in the erenumab group had their migraine frequency decrease to half vs 30% in the placebo group (p=0.01). The patients in the erenumab group had 1.2 less monthly migraine medication days vs 0.6 in the placebo group (p=0.002).⁴

The LIBERTY trial only enrolled patients who failed or could not tolerate 2 or more migraine prophylactic agents. It showed that 30% of patients in the erenumab group had migraine frequency decrease to half compared with 14% in the placebo group (p=0.002).¹⁸

Erenumab has also showed efficacy in reducing frequency of migraines in women with menstrual migraines with the odds of having 50% reduction in migraines 2.8 times more with erenumab than placebo.⁹ Moreover, erenumab showed a decrease of persistent post-traumatic headaches from 16 days to 3 days per month after initiation of the drug.¹³

It also reverts patients from chronic migraines to episodic migraines, which improves quality of life.¹⁵ The agent has a higher benefit risk profile than other prophylactic agents, which supports its specific use for migraines alongside its more benign AE profile.¹⁹

Adherence to oral migraine prophylactic agents can be as low as 17%.²⁰ A monthly injection, such as erenumab, offers an advantage of paramount importance to ensure patients are properly treated.

Due to difference in cost, the AHS recommends a trial of 2 agents (topiramate, valproate, metoprolol, propranolol, or timolol) for 8 weeks each before using erenumab. If a patient has an inadequate response or cannot tolerate those agents, it is reasonable to use erenumab.

In conclusion, erenumab is a monoclonal antibody that acts as a CGRP receptor antagonist. It is effective in reducing episodic and chronic migraines and can be used if other agents are ineffective or intolerable. Its monthly schedule and safety profile are extremely advantageous in treating patients, especially in chronic migraines. Clinicians should consider it for treatment when other options are ineffective.

References

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2. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039.
3. 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.
4. Dodick DW, Ashina M, Brandes JL, et al. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38(6):1026-1037.
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8. Schwedt T, Reuter U, Tepper S, et al. Early onset of efficacy with erenumab in patients with episodic and chronic migraine. J Headache Pain. 2018;19(1):92. Published 2018 Oct 1.
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11. Tepper SJ, Ashina M, Reuter U, et al. Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study. Cephalalgia. 2020;40(6):543-553.
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13. Ashina H, Iljazi A, Al-Khazali HM, et al. Efficacy, tolerability, and safety of erenumab for the preventive treatment of persistent post-traumatic headache attributed to mild traumatic brain injury: an open-label study. J Headache Pain. 2020;21(1):62. Published 2020 Jun 3.
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15. Lipton RB, Tepper SJ, Silberstein SD, et al. Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension. Cephalalgia. 2021;41(1):6-16.
16. Lipton RB, Tepper SJ, Reuter U, et al. Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study. Neurology. 2019;92(19):e2250-e2260.
17. Buse DC, Lipton RB, Hallström Y, et al. Migraine-related disability, impact, and health-related quality of life among patients with episodic migraine receiving preventive treatment with erenumab. Cephalalgia. 2018;38(10):1622-1631.
18. Reuter U, Goadsby PJ, Lanteri-Minet M, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280-2287.
19. Vo P, Wen S, Martel MJ, Mitsikostas D, Reuter U, Klatt J. Benefit-risk assessment of erenumab and current migraine prophylactic treatments using the likelihood of being helped or harmed. Cephalalgia. 2019;39(5):608-616.
20. Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35(6):478-488.