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How CGRPs for Cluster Headache Differ from Migraine Disease

The first CGRP preventive injection medication (Aimovig®) was FDA-approved in 2018, with 2 other similar drugs following suit in the next year and a half: Emgality® and Ajovy®.

The beginning of CGRPs

I was lucky enough to know about these trials as they happened and saw firsthand how my friends with cluster headaches benefited along with patients with migraine disease. I’ll never forget the excitement when Emgality® was approved. This is the first-ever drug to earn FDA-approval specifically for episodic cluster headaches.

The migraine community was excited to have new options too, and it felt like we were embarking on a new age of treatments for headache disorders. But, there were a few issues those of us with cluster headaches faced. The biggest problem was the type of CGRP injectable medication.

The only preventive CGRP approved for cluster headache

Aimovig® and Ajovy® are FDA-approved to treat migraine disease, not cluster headaches. Yet, many of us were prescribed those injections before Emgality®, which is indicated for cluster headaches. That is common for treating our condition because nearly every medication used to abort or prevent attacks is a hand-me-down drug from another disorder, such as epilepsy, bipolar disorder, migraine disease, or high blood pressure. However, Emgality® was the only CGRP injection medication to meet the endpoints necessary to get approval for preventing cluster headaches.

The difference Emgality makes

“7 months on Emgality®, and there has been a definite improvement,” says Leslie Kingston, a cluster headache patient. “I tried Aimovig® for 4 months before Emgality®... Side effects, headaches blasted right through as if the Monster in my head was even more aggressive. My advice? Try Emgality® for 4 months. The longer you take it, the better it works.”

Dosage issues

Another barrier cluster headache patients face in getting Emgality® is that the dosage required is nearly three times that used for migraine disease. The dosage for migraine is 120mg in a pre-filled syringe taken once a month to give you more pain-free days. The dosage for episodic cluster headache is 300mg in three pre-filled syringes taken one after the other once a month to prevent an episodic cycle or end one that has already started. The research that gained FDA-approval for the drug showed that cluster headache attacks per week were cut in half in 71% of patients by week 3.3

What is “CGRP?”

CGRP stands for calcitonin gene-related peptide, which is a neuropeptide involved in the pathophysiology of both migraine disease and cluster headache. In migraine disease, it’s believed that the trigeminal nerve is activated and releases CGRP (among other peptides) to cause inflammation. More CGRPs are released during the migraine attack, which may last 72 hours.2 The trigeminal nerve (along with the hypothalamus and sphenopalatine ganglion, or SPG) also plays a role in cluster headache and releases CGRPs during an attack. Patients who are having active bouts of cluster headaches can be given CGRP to trigger an attack1.

What’s the difference between these medications?

Aimovig®, Ajovy®, and Emgality® work by either blocking the CGRP receptor in the brain or attaching to the calcitonin gene-related peptide to stop the activation of the CGRP receptors and make sure less of it arrives. Emgality® and Ajovy® bind to CGRP peptides, whereas Aimovig® blocks the receptor.

These CGRP medications have similarities and differences in how they work on the brain. The Migraine.com Editorial Team goes into detail about these medications in the above post. Aside from the 3 FDA-approved injection medications, there are CGRP tablets, Nurtec ODT and Ubrevly, and a CGRP IV infusion, Vyepti.

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This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The Migraine.com team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

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