Around thirty-nine million people struggle with migraines, and these headaches result in 1.2 million ER visits. The article explains the role of CGRP inhibitors in the management of migraine pain and also compares the older CGRP antagonists with the new ones.

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More than 90% of patients with migraine can’t function at their jobs. Fortunately, in recent years, new treatments have revolutionised migraine therapy, including calcitonin gene-related peptide (CGRP) antagonists.

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CGRP inhibitors

CGRP is a neuropeptide located in the peripheral and central nervous system that plays a role in pain.

Studies have shown that CGRP is released during migraines, and exogenous administration may induce migraine symptoms, therefore inhibiting CGRP and possibly preventing migraines.

This new class of migraine medications is the first targeted therapy to prevent migraines. It treats either episodic or chronic migraine and acts by inhibiting the CGRP pathway.

There are two isoforms of CGRP: α and β, and they work to dilate the cerebral arteries, as well as to degranulate mast cells. These processes mostly occur in the trigeminal vascular network and could lead to pain.

CGRP antagonists can be taken orally or injected as monoclonal antibodies (biologics). The injected form does not cross the blood-brain barrier and is not metabolised in the liver, making it safe to take with acetaminophen, or for individuals with liver disease.

The biologics eptinezumab, galcanezumab, and fremanezumab target the CGRP molecule as erenumab takes aim at the CGRP receptor.

In various clinical trials, these agents have decreased migraine frequency, alternative medication use, and headache days. CGRP inhibitors lessen headache symptoms in various types of migraines including those with or without aura—as well as chronic, episodic, and medication-overuse headaches.

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Comparison with older CGRP antagonists

Gepants are earlier-generation CGRP antagonists, which are smaller in molecular size and are taken orally.

Several factors lead to their discontinuation in patients including hepatotoxicity and transaminitis, as well as headache, paresthesia, and visual disturbances.

On the other hand, newer CGRP inhibitors, which primarily come as monoclonal antibodies, with the exception of one new oral agent, are safer and better-tolerated, according to the literature.

In the official prescribing information for erenumab, the only adverse effects listed are constipation and injection-site reaction, which occurred in at least 3% of patients in clinical trials. No contraindications were listed.

“The long-term role of nonselective CGRP blockade effects such as pituitary gland dysfunction, ischemic events, hypertension, gastrointestinal disturbances are currently being researched,” wrote the authors of an article published in Innovations in Clinical Neuroscience.

“Prescribing the CGRP inhibitor drugs might improve the quality of life for patients with migraine headaches. Hopefully, they will be a positive influence in the lives of migraine-afflicted people and could prove to be an excellent, safe anti-migraine pharmacotherapy."

— Mohanty, et al.

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Migraine prevention

CGRP inhibitor monoclonal antibodies may be more effective than other drugs in preventing migraines.

“Although being a relatively new class of migraine preventive drugs, monoclonal antibodies blocking the CGRP pathway have an efficacy which is at least comparable if not higher than those of the currently used preventive drugs,” wrote the authors of a study published in The Journal of Headache and Pain.

“Moreover, the robustness of this efficacy signal is substantiated by several randomised clinical trials each including large numbers of patients,” they continued. “In addition, because of their excellent tolerability and with long-term safety data emerging, they seem to have an unprecedented efficacy over adverse effect profile, clearly resulting in an added value for migraine prevention.”

On a related note, the FDA approved atogepant, an oral CGRP antagonist, in September 2021 for the preventive treatment of migraine. This is the first CGRP agent designed specifically for the prevention of migraines.

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What this means for you

Most physicians encounter patients with migraines. It’s important to know that CGRP inhibitors are a promising new treatment with few adverse events. They may provide the best prevention against this incapacitating illness. A recently approved oral CGRP antagonist, atogepant, may provide further relief in the prevention of migraines.

This article was originally published on 1 October 2022.

Disclaimer: This story is contributed by Naveed Saleh and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.