CGRP Inhibitors for Preventing Migraines

Calcitonin gene-related peptide (CGRP) inhibitors are a relatively new type of medication approved by the Food and Drug Administration (FDA) to treat and prevent migraines with or without aura. They also can reduce the number of days per month a person gets migraine headaches.

Currently, Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), and Vyepti (eptinezumab) are taken as monthly injections for prevention, while Nurtec (rimegepant) and Qulipta (atogepant) are pills taken for prevention. Nurtec and Ubrelvy (ubrogepant) are approved to treat migraine headaches in the moment.

They're proving to have distinct advantages over more classic prophylactic migraine drugs—oral migraine preventive medications (OMPMs) such as beta blockers, anti-seizure medications, and antidepressants.

Notably, CGRP inhibitors don't cause the same types of unpleasant side effects that often make OMPMs difficult or even impossible for some people to take. In fact, in clinical trials, CGRP inhibitors have been found to have very minimal side effects altogether.

If you have chronic or episodic migraines and have found that OMPMs don't work well for you or cause side effects that you can't tolerate, you may want to consider trying a CGRP inhibitor.

CGRP and Migraine Symptoms

CGRP is a protein present in the trigeminal nerve, a cranial nerve that is responsible for facial sensation. It has been found to play a role in migraines by causing dilation of cranial blood vessels. CGRP may also mediate the transmission of pain from the dilated vessels to the brain and promote neurogenic inflammation.

As a migraine attack progresses, the brainstem becomes sensitized, leading to a vicious cycle of head pain and an increased sensitivity to the environment. This is why people often find light, noise, or odors to be unbearable during a migraine attack.

Preventive migraine medications that target this protein work by blocking the docking site of the CGRP receptor (Aimovig and Vyepti) or the CGRP protein itself (Ajovy and Emgality). They are in a class of biologic drugs called monoclonal antibodies.

Aimovig, Ajovy, Vyepti, and Emgality

These four CGRP inhibitors that have been approved by the FDA for preventing migraine headaches share several similarities:

Route of Administration

Aimovig, Ajovy, and Emgality are taken via subcutaneous injection. This means they're injected via a shot with a thin needle into fatty tissue (rather than deep into muscle). Most people give themselves these injections into the thigh or belly after being taught how by a medical practitioner. These CGRP inhibitors can also be injected into the upper arm by someone else.

Vyepti works a little differently in that a healthcare provider administers it intravenously (by IV). The infusion is administered slowly over the course of 30 minutes.

Timing

None of the injectable CGRP inhibitors are taken every day. Aimovig and Emgality are taken once a month as one or two successive shots, depending on the dose. Ajovy is taken once a month (one injection) or once every three months (three injections, one after the other). Vyepti is administered once every three months.

Side Effects

For Aimovig, Emgality, and Ajovy, the main side effects are redness, pain, or swelling at the injection site—all common and temporary occurrences after an injection of any type. Aimovig also has been associated with constipation.

For Vyepti, the most common side effects are stuffy nose, sore throat, and allergic reactions.According to reports, most allergic reactions occurred during the patient's infusion and were not serious.

Although less common, taking a CGRP inhibitor can cause serious allergic reactions. You should seek medical attention right away if you start to have symptoms of an allergic reaction, such as a rash, hives, itching, difficulty breathing, and swelling of the face, tongue, or throat.

Effectiveness

For a report published in July 2018, the Institute for Clinical and Economic Review (ICER) reviewed 11 clinical trials of CGRP inhibitors for preventing chronic migraine and eight trials of CGRP inhibitors for preventing episodic migraines.

The ICER found that, overall, migraine patients who took CGRP inhibitors had greater reductions in headache days per month versus taking other preventive medications. What's more, there were "higher odds of 50% response, and greater reductions in days using acute medication per month for all of the interventions versus placebo."

Additionally, a study of adult patients with chronic migraine found that Vyepti reduced migraine frequency by at least 75% in 40% of the participants. One treatment of Vyepti was shown to significantly reduce migraine frequency and improve quality of life for up to three months at a time.

In short, all four FDA-approved CGRP inhibitors have earned an important spot in the arsenal of medications that prevent migraines.

Nurtec, Qulipta, and Ubrelvy

The FDA approved Nurtec to prevent migraine headaches and treat them after they start. Ubrelvy was also approved to treat migraines after they start, while Qulipta was approved to prevent them. These three FDA-approved CGRP inhibitors are taken orally.

A Word From Verywell

There's no question managing migraine headaches can be tricky. How people experience them and the way they respond to treatments can vary widely. Since many patients find OMPMs intolerable, the development of drugs with fewer side effects is a welcomed advancement in migraine prevention. If you've been unable to find a medication that keeps your headaches from occurring, it may make sense to talk to your healthcare provider about trying a CGRP.