Perhaps the most significant breakthrough in migraine treatment of the last two decades, anti-CGRP (calcitonin gene-related peptide) therapy has provided considerable relief to some people with migraine, helping to prevent migraine and make migraine less severe when it does occur.
In 2018, anti-CGRP therapy became the first treatment approved by the Food and Drug Administration specifically to prevent chronic and episodic migraine. This treatment can be both a preventative or abortive therapy depending on the specific drug prescribed. Anti-CGRP therapy is also referred to as CGRP inhibitor or CGRP antagonist treatment.
Although scientists still don't understand the exact mechanisms of migraine, one discovery started to shed some light on it: calcitonin gene-related peptide. This protein causes inflammation and pain in the nervous system when a person experiences a migraine. In addition, CGRP is thought to play a role in arthritis pain and itching associated with skin disease, according to research published in the journal Physiological Reviews.
CGRP is believed to be involved in both chronic and episodic migraine. Chronic migraine is defined as having 15 or more headache days per month, and episodic is fewer than 15 days per month. A study published in Neurology found that women with chronic migraine had higher levels of CGRP in their blood than women who experienced migraine less frequently.
After discovering CGRP, researchers investigated how to apply this knowledge to create better migraine treatments. "The most important thing that CGRP has done is to offer a specific target for the treatment of migraine," says Peter Goadsby, MD, PhD, DSc, professor of neurology at the David Geffen School of Medicine at UCLA in Los Angeles, on the Medical Board at Mable, and one of the researchers who first identified the protein. Dr. Goadsby has been researching CGRP since 1985. "Prior to the advent of this, preventive treatment of migraine was done using medicines designed for other purposes," he says.
These other preventive treatments included blood pressure medicines like beta-blockers, propranolol; antidepressants; and anti-epilepsy drugs. "The problem they brought was twofold: One, it left an impression that migraine therapy was rather ragtag or happenstance because there was no specific preventive treatment. And two, it brought side effects," says Goadsby. Depending on the medication, these could include dizziness, dry mouth, and trouble focusing.
In contrast, CGRP is specifically involved in migraine. "If you block CGRP, it reduces the amount of migraine without bringing any other baggage – particular side effects," Goadsby says.
Currently, there are seven types of anti-CGRP migraine treatments available: rimegepant (Nurtec), ubrogepant (Ubrelvy), erenumab (Aimovig), epitinezumab (Vyepti), fremanezumab (Ajovy), galcanezumab (Emgality), and atogepant (Qulipta). These treatments are either taken orally every day or self-injected, usually once a month.
These therapies can work differently, depending on their underlying mechanism. Some block the sites around and in the brain where GCRP attaches (known as the gepants). Others bind to the CGRP molecule (known as the monoclonal antibodies), preventing it from working.
Technically, anyone who has migraine can be a candidate for anti-CGRP therapy; however, it isn't used as a first-line treatment. You first need to try – and fail – at least two other preventive migraine medicines before a health insurance company will cover them. "Failing" at a drug simply means that it doesn't help lessen your migraine frequency and/or severity enough to improve your quality of life after three months of continual use at the optimal dose for you.
There isn't a surefire way to know who may benefit most from anti-CGRP therapies because there isn't a way to understand how well any migraine treatment will work for an individual. "One of the limitations we have at the moment in therapy is we can't tell who, when they walk in the door, will respond to one therapy or another," Goadsby says. "So if someone comes in and they've got migraine, anti-CGRP therapies would likely work in many of them – but I can't tell who they are."
However, researchers are working to change that. Mable's proprietary DNA test can help determine which migraine medicines are most likely to help you while causing the fewest number of side effects, based on your genetic makeup. To find the most customized treatment for your migraine, start filling out Mable's online questionnaire.
Since anti-CGRP therapies are newer medications, the long-term risks aren't yet known, if there are any.
CGRP plays a role in widening your blood vessels, which affects your blood pressure—as such, anti-CGRP therapies lower CGRP levels in your body, affecting your blood pressure and heart. However, a study published in the International Journal of Neurology and Neurotherapy found no cardiovascular severe side effects in people who used anti-CGRP therapies in clinical trials, including those who had previous cardiovascular risk. But suppose you have uncontrolled high blood pressure. In that case, Goadsby says it's essential to treat that first before starting an anti-CGRP therapy.
Overall, anti-CGRP therapies appear to be very safe for most people. When administering the drug, a small number of people report pain at the injection site. In addition, pregnant women or trying to become pregnant are advised not to take anti-CGRP therapies since the risks are unknown to the mother or baby.
As mentioned, anti-CGRP therapies are used in people who haven't found success with other migraine treatments. Anti-CGRP therapies can provide welcome relief for some, but not all, of those who try them. "There are many patients who don't respond the way I'd like them to; they don't get a response," says Goadsby. "I think that the anti-CGRP therapies tend to either work rather well – or not work at all."
Goadsby says the speed with which anti-CGRP therapies take effect can vary. "The earliest onset that I've seen is days, and I've also seen it take two or three months," he says. A study published in The Lancet found that one-third of participants who tried anti-CGRP therapies had a 50 percent or more significant reduction in the number of migraine days per month after three months. "People for whom anti-CGRP therapies don't work well are very disappointed because they're new drugs, and there's quite a bit of hype around them," he adds.
For those who do get relief from them, anti-CGRP therapies appear to remain effective over time, without any new side effects. "If you get the medicine right at the right dose, the person can tolerate it over a long period of time," Goadsby says. And this can mean a significant improvement in your quality of life. "That's the big deal – the ability to put patients back on track, to give them the things back that they want; the predictability, the control of their life, and feeling like a normal person," he says.
Health insurance companies are less willing to cover anti-CGRP therapies because they are expensive. Out of pocket, they generally cost about $600 a month. The cost will likely go down over time once the medications become generic.
Suppose you've been discouraged by other migraine treatments that haven't worked for you in the past. In that case, anti-CGRP therapies may be worth considering. "Consumers ought to know that yesterday is not tomorrow," Goadsby says. "There's a new therapy that has a reasonable chance of working and which you will be able to tolerate. It will not give you any days back, but this treatment may help you get back control of your life from migraine."
If you're interested in trying anti-CGRP therapy, talk to your doctor about whether or not you might be a candidate. Remember that you'll probably need to have tried at least two other migraine medications without success to get insurance coverage for them.
Before you commit to anti-CGRP therapy or another migraine treatment, it can be good to investigate which migraine medications are more likely to work for you. Mable's DNA test can help determine if anti-CGRP therapy or another treatment is more likely to help with your unique genetic makeup. Fill out the online migraine questionnaire to start the process.
1. American Migraine Foundation, “What to Know About the New Anti CGRP Migraine Treatment Options.” https://americanmigrainefoundation.org/resource-library/anti-cgrp-treatment-options/
2. Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94(4):1099-1142. doi:10.1152/physrev.00034.2013
3. Interview with Peter Goadsby, MD, PhD, DSc, professor of neurology at the David Geffen School of Medicine at UCLA in Los Angeles
4. Eva Cernuda-Morollón, Davinia Larrosa, César Ramón, Juan Vega, Pablo Martínez-Camblor, Julio Pascual. Neurology Oct 2013, 81 (14) 1191-1196; DOI: 10.1212/WNL.0b013e3182a6cb72
5. Healthline, "CGRP Migraine Treatment: Could It Be Right for You?" https://www.healthline.com/health/migraine/cgrp-migraine
6. Boldig K, Butala N (2020) Migraines and CGRP Monoclonal Antibodies: A Review of Cardiovascular Side Effects and Safety Profile. Int J Neurol Neurother 7:101. doi.org/10.23937/2378-3001/1410101
7. Uwe Reuter, Peter J Goadsby, Michel Lanteri-Minet, Shihua Wen, Peggy Hours-Zesiger, Michel D Ferrari, Jan Klatt,Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study, The Lancet,Volume 392, Issue 10161, 2018, Pages 2280-2287, ISSN 0140 -6736, https://doi.org/10.1016/S0140-6736(18)32534-0