CGRP Inhibitors for Migraine


Jessica Ailani, MD, of MedStar Health, describes the mechanisms of action and indications for use of currently available CGRP inhibitors for migraine.

Philippa Cheetham, MD: Let’s drill down for a minute and examine this category of medication. When were these drugs first approved? Obviously, now there are a number of brothers and sisters in the same family. Have the new kids on the block meant that the initial CGRP [calcitonin gene-related peptide] inhibitors are not the best choice? What is the difference between these? How long have you been using them regularly in clinical practice?

Jessica Ailani, MD: There are 4 CGRP monoclonal antibodies available in clinical practice. The first that came to market, in 2018, was erenumab, and it is sold commercially as Aimovig. The other 3 that have come to market are a little different than erenumab. CGRP is this protein that can cause lots of havoc in the brain. It can irritate, cause pain, activate pain structures, and is known to be a part of what is happening in migraine. It has been shown that, if we can block its activity, we can reduce migraine frequency, and also we can treat a migraine attack when it is occurring.

If we think of CGRP as a car, and a car has to park in a garage. If you stand in front of the garage and you do not let the car park, then it is impossible for the car to go to where it needs to go—that is erenumab. It is blocking where CGRP has to go, it blocks the receptor. If you’re a 15-ton weight that sits on top of the car, crushing it, or if you sit on the car in very heavily, then that is other 3. They stick to the CGRP and do not let it move where it needs to go. Either way, you are blocking CGRP activity, so you are blocking its ability to cause a migraine or do other activities in the body.

The other 3 medications on the market are only newer than erenumab by a little bit. Two of them, fremanezumab and galcanezumab, were FDA approved just months after erenumab, so those 3 have been around since 2018. The newest on the market is eptinezumab, which was approved in 2020 during the midst of the pandemic. It is the only one that is an intravenous infusion. That makes it a little different.

Philippa Cheetham, MD: Correct me if I’m wrong, but this is a drug that has efficacy over a number of months, is that correct?

Jessica Ailani, MD: Yes. Eptinezumab is quarterly. It is dosed every 3 months, and you get 1 injection over 30 minutes. Then for 3 months you have migraine protection. It does not get rid of the migraine, but all of these medications have shown to significantly reduce migraine attacks for patients compared with not taking a medication or taking a placebo. It reduces attack frequency, if you’re someone who has episodes of migraine, by about 4 days per month. If you are someone who has chronic migraine, it can cause you to experience somewhere in the ballpark of about 8 fewer days of migraines per month. It is a pretty significant reduction in the number of days of migraine.

Philippa Cheetham, MD: Thank you for watching NeurologyLive® Cure Connections®. If you enjoyed the program, please subscribe to our e-newsletter to receive upcoming programs and other great content right in your inbox. Thank you so much.

Transcript Edited for Clarity

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