Calcitonin gene-related peptide (CGRP) inhibitors are a relatively new type of medication for preventing chronic and episodic migraine headaches (with or without aura). They’re proving to have distinct advantages over more classic prophylactic migraine drugs—the so-called 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 clinical trials, CGRP inhibitors have been found to be remarkably free of major side effects.
They also can be highly effective at warding off migraines and significantly reducing the number of days per month a migraine sufferer has headaches. Currently, three CGRP inhibitors have been approved by the U.S. Food and Drug Administration (FDA): Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).
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. This overview should provide enough information for you to make an informed decision with the guidance of your doctor.
CGRP and Migraine Symptoms
CGRP is a protein in the brain and nervous system that plays a part in the transmission of pain and, studies show, the progression of migraine headaches. During a migraine attack, it’s believed blood vessels are triggered to dilate, which in turn leads to the release of CGRP from the trigeminal nerve—a cranial nerve that supplies sensation, including pain, to areas of the face.
CGRP may then lead to further dilatation of the cranial blood vessels, as well as 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. They are in a class of biologic drugs called monoclonal antibodies, which means that rather than being synthesized from chemicals they are produced by altering the DNA inside of living cells.
Comparing CGRP Inhibitors
The three CGRP inhibitors that have been approved by the FDA for preventing migraine headaches—Aimovig, Ajovy, and Emgality—share several similar advantages:
Administered by subcutaneous injection. This means they’re “taken” 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. CGRP inhibitors also can be injected into the upper arm by someone else.
Timing. None of the CGRP inhibitors are taken every day. Aimovig and Emgality are taken once a month a s one or two shots right after the other, depending on the dose. Ajovy is taken once a month (one injection) or once every three months (three injections, once after the other).
Mild side effects. The main ones 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, cramps, and muscle spasms.
Less often, someone may experience an allergic reaction after a CGRP inhibitor shot, particularly with Ajovy. Symptoms such as a rash, hives, itching, swelling of face, tongue, or throat, or difficulty breathing. If you take an CGRP inhibitor and experience any of these, you should get immediate medical attention. Note that these more serious side effects can occur days or even up to a month after taking the medication.
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 percent response, and greater reductions in days using acute medication per month for all of the interventions versus placebo.”
In short, all three FDA-approved CGRP inhibitors, as well as another, eptinezumab which is still being studied, have earned an important spot in the arsenal of medications that prevent migraines.