The Patient’s Perspective (Carolyn Rivkees):

It’s a really exciting time for people with migraine. 

For the first time in decades, we now have treatment options whose primary use is actually for migraine – unlike the drugs commonly prescribed for migraine designed for other conditions, like blood pressure or epilepsy. These new drugs, the anti-CGRPs, are more targeted, have fewer side effects than many medications, and can be used by more people.

If, like me, you’ve “failed” traditional migraine treatments, have some hope that the anti-CGRPs might be the key to future relief. These new medications are a critical part of my preventative and acute treatment plans and I rely on them both to manage my chronic migraine.  

This new advance in migraine medicine has to do with the CGRP, or calcitonin gene-related peptide. CGRP is a protein in the brain involved in generating head pain associated with migraine. Researchers have developed therapies that work by targeting this specific protein, either by blocking the protein itself or blocking the receptor it attaches to.

For years, I lived with chronic migraine and didn’t get adequate relief from traditional migraine medications. I was especially excited about trying this new class of drugs and about their minimal side effect profile, which made me less nervous about trying a new treatment.

Out of the preventative anti-CGRP options, I’ve tried the following:

• Erenumab (brand name: Aimovig®)
• Galcanezumab (brand name: Emgality®)
• Eptinezumab (brand name: Vyepti®)

I decided to first try Aimovig and Emgality, which are self-administered via a monthly injection. I stayed on each drug for around 5 months before switching to another medication, as I wanted to give the drugs enough time to make an impact. While both treatments didn’t change the intensity or duration of my migraine attacks, I did not experience any side effects – something I considered a major victory. Even though the medications didn’t help me, they didn’t hurt! 

Vyepti is a little different from the other two: it’s administered via a 30-minute IV infusion, and I continue to receive it every three months. Without any drug-related side effects, Vyepti helps my attacks to become less severe, minimizing my pain and other unpleasant migraine symptoms.

I’ve also tried these oral anti-CGRPs, which you take on an acute basis:

• Rimegepant (brand name: Nurtec™ ODT)
• Ubrogepant (brand name: Ubrelvy®)

I experienced no relief when taking Ubrelvy, but it still gave me such peace of mind not to experience any negative side effects. On the other hand, Nurtec continues to be the best acute medication I’ve ever tried for migraine relief. While the medication may not entirely stop a migraine attack from unfolding, I can usually rely on the medication to provide substantial pain relief.

My experience also shows that if one anti-CGRP medication doesn’t work for you, it doesn’t mean that another won’t be able to help. So keep trying and have an open mind!

I’ve also been lucky – I didn’t have a problem getting my insurance to cover these treatments. Getting your insurance to cover an anti-CGRP treatment usually means having to prove that you’ve already unsuccessfully tried two or three more traditional preventive options. If like me, you’re a chronic migraine patient who has been searching for relief after trying several different therapies, then you’re probably a great candidate for an anti-CGRP. 

The Neurologist’s Perspective (Thomas Berk, MD):

“Traditional” Migraine Medications

For years, headache specialists have needed to choose medications for migraine that were far from perfect. Preventive medications for migraine were either anti-seizure medications, antidepressants, or blood pressure medications, and most acute medications were either anti-inflammatories or anti-nausea medications. When medications are less specific for migraine, the likelihood of side effects is greater and for benefit is lower. Even the patients who have improved on these “traditional” migraine preventive options experienced significant side effects, and many providers have had to have the difficult discussion of whether we should continue these medications in light of these side effects.  

History of Anti-CGRP Medications

Over the past 20 years, we have learned a tremendous amount about what happens in the brain during a migraine attack. We have recognized specific chemicals in the brain that propagate the activity of migraine and lead to some of the most common features of migraine such as sensitivities to lights, sounds, smells, and nausea. CGRP is not the only protein that leads to the development of these migraine symptoms, but since it was recognized, it has become a target for treatment.  

The first anti-CGRP medication was an oral medication developed by Merck that was initially met with optimism, but the initial trials were stopped early due to a high incidence of liver toxicity. Due to these concerns, alternative ways to target and block CGRP were developed - via antibodies. These medications are not metabolized by the body at all and have never been associated with these side effects. In 2018, the first three of these anti-CGRP medications were approved for the prevention of migraine - Aimovig, Ajovy, and then Emgality.  

Aimovig, Ajovy and Emgality

The differences between these medications are relatively minor. Aimovig blocks the receptors that CGRP binds to on the body’s cells, Ajovy and Emgality both block the protein CGRP itself. Aimovig is associated with more constipation and hypertension, likely because it binds to the receptors rather than blocking the proteins themselves. The most common side effect of all of these medications is an injection site reaction, a sore or itchy feeling lasting for a day or two at the injection site.  

Vyepti 

Vyepti is similar to the other three antibody medications since it also blocks the CGRP protein, but is given as a once-every-three-month IV infusion instead of a once-monthly injection. Ajovy does have the ability to give three injections on one day that will last all three months as well. Vyepti also has two doses: 100 and 300mg infusions. The side effect profile is similar to the injections, though upper respiratory symptoms are more common though with Vyepti. 

Nurtec and Ubrelvy

In 2020, two oral medications became approved for the acute treatment of migraine - Nurtec and Ubrelvy. Both of these target the receptors of CGRP and because they are small molecules rather than antibodies, they are metabolized by the liver. There have not been any indications that either of these medications is associated with liver toxicity issues, and the main side effects are sedation and nausea. They are slower in onset than the triptan class of medications but appear to be more effective at 24 and 48 hours, making it less likely that your migraine will lead to a multi-day affair, and that you will have to take more medications to treat that migraine attack. 

Nurtec was recently approved to be taken every other day as prevention for migraine, and a new oral preventive has been approved as well called Qulipta.  

Efficacy

The efficacy of the medications is variable but can be profound. A small percentage of people who use these medications are considered “super responders” - they can decrease from a high frequency of migraine to nearly none. The majority of people have a decrease of 4-8 migraine days per month, which can be a significant improvement, especially if you experience less than 10 or so days of migraine per month. If your headache frequency is higher than that, for instance, 15 or more days per month, that decrease may not be enough. 

There is a growing body of evidence that the use of anti-CGRP medications in addition to Botox or other preventive options can be synergistic and decrease migraine frequency more than each option would alone. Many specialists will consider this, even if you have already been on both of these medications separately. There may be push-back from your insurance, though, as they don’t like to cover multiple expensive medications. 

Because blocking CGRP, if anything, helps prevent migraine, there appears to be no association between the use of oral anti-CGRP medications and “rebound” or medication overuse headaches.  

There is a lot that is not known now about the use of anti-CGRP medications to both prevent and treat acute attacks at the same time, and you should ask your doctor what their policy regarding the use of multiple medications in the anti-CGRP class.  

Need to speak with a neurologist specializing in headache medicine? Join Neura Health, and schedule a same-day or next-day video appointment to talk through your questions about headache medications and treatment options that could be right for you.