Preventing Migraine with CGRP Monoclonal Antibodies


Expert neurologists discuss the use of CGRP monoclonal antibodies to prevent migraines.

Jessica Ailani, MD: Speaking of erenumab [Aimovig]. Stephanie, I’m going to turn to you first. Let’s do a quick overview of the 4 different CGRP [calcitonin gene-related peptide] monoclonal antibodies that are FDA [Food and Drug Administration] approved for the prevention of migraine. Just to remind our audience, these are erenumab, fremanezumab [Ajovy], galcanezumab [Emgality], and eptinezumab [Vyepti], which are FDA approved for preventive treatment in adults for both episodic and chronic migraines. We’re just going to quickly talk about comparing the outcomes for preventive treatment and side effects, and we’re going to go through the 4 [medications] very briefly. Stephanie and Rebecca, maybe you want to talk through them if you both want to have a little discussion about them.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: You already gave the overview of the names. There are some subtle differences between and among them all. Erenumab was approved first. It is a subcutaneous monthly injection available in 2 dosing regimens, either 70 milligrams or 140 milligrams monthly, which is best dosed every 28 days to try to get away from that wearing off effect. If you can sync up, just going back to the prior topic, if you can sync it up that way and also sync it so it’s not coinciding with their menstrual cycle for your women who have menstrual-related migraine, that’s another challenge that we face. Anyway, the mechanism for erenumab is to stick to the receptor for CGRP. All of the others stick to CGRP itself. The end result is the same. The lock can’t fit in the key, but the effects that an individual patient may experience could vary and we’re still trying to sort that out. We may get some clue from the adverse events, which have been reported, in clinical trials and post-marketing.

Across the board, the subcutaneous injectables, erenumab, fremanezumab, and galcanezumab, all came out the same year. Injection site reaction is the predominant adverse event and that’s just a localized reaction like a welt that can be itchy, red, swollen, painful, etc. We almost expect it. It seems to occur randomly and does not indicate that there is an allergy to that medication. Allergic reactions are reported. We call that hypersensitivity to the product but that’s a bit different.

Where erenumab is a little different in terms of the adverse events in the clinical trials, constipation was also reported. Now in post-marketing, since there have been so many exposures, we’re getting signals for hypertension, signals for alopecia, and constipation that can be severe enough to lead to bowel obstruction even requiring surgery. These have all made it into the label as updates for cautions with this drug.

For the other 3, as I said, they all antagonize or stick to the peptide themselves, and the dosing is monthly for both of the other subcutaneous injectables, galcanezumab, and fremanezumab. But fremanezumab also has the option of dosing it quarterly. Instead of taking a single dose every 4 weeks, you can do a triple dose every 12 weeks or every quarter. They call it monthly vs quarterly. Now, eptinezumab is also a blocker of the peptide itself but it’s intravenous and dosed in a quarterly fashion. There are 2 dosing options available, 100 milligrams and 300 milligrams.

The bottom line is that they all work in the clinical trials for both episodic migraine and chronic migraine when you look at primary end points of reducing migraine frequency. When you look at other secondary end points like 50%, 75%, 100% reduction, this is one of the reasons we’re now raising the bar for what we expect from preventive treatment. We used to be happy with 25% to 30% improvement, but that’s not success at all anymore. But measures of disability, function, and quality of life are also very, very important.

Jessica Ailani, MD: Thank you to our audience for watching this Neurology Live® Peer Exchange. I hope that you’ve enjoyed watching this program as much as we’ve enjoyed spending this time together. If you have enjoyed this content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.

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