What Are CGRP Antagonists?

As doctors and researchers continue to improve their understanding of migraines, newer and more effective treatments are emerging. In 2018, migraine treatment saw one of its biggest advancements as the FDA approved a new class of medications, known as CGRP antagonists, for the treatment of migraines.

This was monumental for a couple of reasons. For one, these CGRP antagonists were the first drugs specifically designed to manage the frequency, duration, and intensity of migraines. The other treatments doctors have been prescribing over the years were originally designed for other uses, such as the treatment of seizures and depression. Also, CGRP antagonists seem to be long-lasting and easy to manage.

If you’re a migraine sufferer, however, you probably have a few more questions before you’re ready to say “sign me up.” Keep reading; we’ll dig deeper into these new CGRP antagonists, how they work, and how to determine if they’re right for you.

There are three FDA-approved medications in this class: Aimovig, Ajovy, and Emgality. The three were released within months of each other in 2018, and they have very similar mechanisms of action, although there are some differences. All three medications are injectable. And no, you do not need to see your doctor every time you need an injection. You can self-administer the medication at home.

How Do CGRP Antagonists Work?

To understand how these medications work, you first need to understand a little about CGRP and how it works in the body. CGPR stands for “calcitonin gene-relate peptide.” This is a small protein that binds to receptors on the cells of various tissues. When it does bind to such a receptor, it passes on a specific message. That message varies depending on the tissue, but when CGRP binds to a receptors on certain nerves and blood vessels, it carries a message of pain and can lead to migraine attacks.

The word “antagonist” means “works against,” so CGRP antagonists are medications that work against the action of CGRP. They can do so either by binding to the CGRP receptors so that CGRP is unable to bind, or by binding to the CGRP molecules themselves, making those molecules unable to bind to the receptors.

All three of the FDA-approved CGRP antagonists are monoclonal antibodies, which just means they are antibodies designed to bind to just one, single protein in the body — either the CGRP protein itself or a protein at the CGRP receptor site.

When a CGRP antagonist prevents CGRP from binding to certain receptors, the messages that would otherwise lead to migraine symptoms are not passed on, which leads to a reduction in migraine frequency and severity.

How Do the Three Medications Differ?

Although Ajovy, Aimvog, and Emgality are very similar, there are a few key differences to note.

Ajovy and Emgality work by binding to CGRP itself. The third medicaton, Aimvog, works by binding to and blocking the CGRP receptor.

Aimvog and Emgality need to be administered monthly. Ajovy can sometimes be administered less frequently — some patients only need injections every three months.

The cost of all three medications is comparable, and they are all easy to administer at home, using a pre-filled syringe, auto-injector, or pen.

How Are the Medications Administered?

Your doctor can show you how to administer the medication so that you feel confident. It’s a subcutaneous injection, meaning that you administer it under the skin — not in the muscle or blood vessel like some other injections. When you pick up your medication, it will already be pre-measured in a syringe or auto-injector, so you do not have to worry about getting the proper dose.

All three drugs can be administered into the thigh, upper arm, or belly. Emgality can also be administered in the buttocks.

How Effective Are CGRP Antagonists?

The clinical trail results have been very positive. In one 3-month study, patients who previously had 15 or more headache days per month experienced 6 – 7 fewer migraine days when taking Aimovig. About 40% of people cut their migraine days in half over that 3-month period. Similar results were seen in clinical trials featuring Ajovy and Emgality. Many patients who have failed to find relief with other common migraine treatments, such as Botox and topiramate, experience relief from CGRP antagonists.

Are There Any Serious Side Effects to Worry About?

So far, most of the side effects experienced by patients taking CGRP antagonists are minor. Some patients experience itching and irritation of the injection site or muscle cramps after their injections. Constipation is also pretty common, but it’s easily managed with lifestyle changes like consuming more fiber-rich foods and drinking more water. If one of the CGRP antagonists causes constipation, switching to a different one may alleviate this problem.

Since these drugs are relatively new to the market, not much is known about the effects of long-term use. Since CGRP is a molecule that is active in various body systems — not just in the nerves and blood vessels — it is possible that long-term use could have some unwanted side effects that have not yet been revealed. For example, since the intestinal lining contains a lot of CGRP receptors, there is some concern that long-term use of CGRP antagonists could lead to IBS and other bowel disorders. These effects have not been confirmed in clinical trials, but they are something to be aware of and to discuss with your doctor when considering the use of CGRP antagonists.

What Advantages Do GRRP Antagonists Have Over Other Migraine Treatments?

The fact that you only have to administer these medications once a month is definitely nice! You do not have to remember to take a pill daily or even visit your doctor’s office regularly, as you do for Botox injections.

CGRP antagonists tend to have fewer side effects than other common migraine medications, so if you’ve suffered side effects like dizziness, weight chances, or low blood pressure with other migraine drugs, trying CGRP antagonists may be a smart choice.

These medications are also approved for the treatment of both chronic and episodic migraine. So even if you have fewer than 15 migraines per month — which would be diagnosed as episodic migraines — this is a viable treatment option. Botox injections, on the other hand, are only FDA-approved for the treatment of chronic migraine.

Are There Any Downsides of CGRP Antagonists?

As discussed above, the biggest concern with these medications is that they are relatively new, and long-term side effects are not well known. This is just something to be aware of and to monitor if you and your doctor decide to try these drugs.

It’s also worth noting that the clinical trials for these drugs did not include a lot of older adults, so if you are retirement age or older, you may want to proceed with a little more caution. At least start off at the lowest possible dose, and go from there.

Are you a migraine patient who would like to learn more about CGRP antagonists and perhaps give them a try? Contact me, Dr. Risa Ravitz, for a consultation. My online practice makes migraine management convenient, affordable, and easy to customize.

What Are CGRP Antagonists?