CGRP Monoclonal Antibodies for Preventive Treatment of Migraine


Andrew C. Charles, MD; Bradley Torphy, MD; and Jessica Ailani, MD, review current FDA approved CGRP monoclonal antibodies available for the preventive treatment of migraine.

Jessica Ailani, MD: Speaking of CGRP [calcitonin gene-related peptide] monoclonal antibodies, Andy, I thought I’d bring it back to you. Could you give us a brief overview of the 4 CGRP monoclonal antibodies and their mechanism of action? We know that they’ve all been shown to be effective in preventing migraine across the spectrum of episodic or chronic, but where are they working and how are they given?

Andrew C. Charles, MD: Erenumab [Aimovig], which was the first 1 that we had available, is a monoclonal antibody targeting the CGRP receptor. Three others are targeting the CGRP peptide. The other 3 are fremanezumab [Ajovy], galcanezumab [Emgality], and eptinezumab [Vyepti]. The fremanezumab and galcanezumab are given by subcutaneous injection either monthly, or in the case of fremanezumab, also potentially every 3 months. And then there’s eptinezumab, which is given intravenously [IV] every 3 months. There’s a difference in terms of their receptor vs peptide targets. And they’re also fundamentally different molecules as well, based on the epitopes on CGRP that the antibodies find. Other components of the antibodies getting into the weeds there’s things like differences in this Fc [fragment crystallizable] region of the antibody that changes processing and half-life. Even though as a class they are all targeting CGRP signaling, they’re fundamentally different molecules. And in the case of erenumab, it has a different therapeutic target.

Jessica Ailani, MD:Going back, Brad, to the idea of choosing, how do we use consensus statements then to decide between using a more traditional preventive, like topiramate or propranolol to 1 of the CGRP monoclonal antibodies like erenumab or galcanezumab to atogepant [Qulipta], which I don’t think made it to the consensus statements as they were? It was so new. But how would one use a consensus statement in those ways? How does it help us in suggesting where to start in a patient who’s brand new? I should say, in a naive patient, not in someone who maybe comes to 1 of our clinics.

Bradley Torphy, MD: As we alluded to earlier, you specifically alluded to earlier, with the NHF [National Headache Foundation] guidelines, the National Headache Foundation stresses that the decision should be a collaboration between the provider and the patient. Not based on some step care model. And when we think about our traditional older treatments for migraine, and I used to say, and certainly would share with medical students and residents, if we can hit 2 birds with 1 stone, fantastic. If a patient’s overweight, then topiramate is a great choice. If the patient has some anxiety, then propranolol may be helpful. It becomes more challenging, I suppose, when we get to the newer treatments because there’s not so much collateral effect, collateral damage, or benefit to that end. If we look at it through the lens of, OK, well, these are well tolerated. However, there are some nuances with adverse effects. Certainly, with the SubQ [subcutaneous] injections, injection site reaction is the leading adverse reaction for any of the SubQ injections. But erenumab does have a potential for constipation. And there’s a label update that episodes of serious complication can occur. If the patient has a history of IBSC and that’s a significant problem for the patient, well, then maybe that would possibly steer the discussion with the patient toward maybe 1 of the other options. What I’ve found that I’ve been doing lately with the advent of the atogepant, because it’s an oral option, and of course, rimegepant [Nurtec] has had every other day oral option for several months now, is really let the patients be a part of that decision. Is the patient comfortable with a once a month or once every 3-month SubQ injection at home? Would she prefer to take a tablet, or would she be open to the idea of an IV? How wonderful it is that we have these options that we can have that discussion with the patient? I’m sure my colleagues would agree. If the patients are involved in the decision, they’re going to have a much better feel. They’re going to be much more likely to be adherent and going to have better outcomes. As we say, there’s never been a great time to have migraine, but certainly, there are more options for people living with migraine today than 5 years ago or even 3 years ago.

Jessica Ailani, MD:Yes. Thank you. These are vital points. When patients are part of the decision-making process, we have data in general, not necessarily in migraine, that suggests that they’re going to be more likely to adhere. But they’re also going to be more satisfied with the treatment they’re receiving because they’re a part of the choice and that their regret and their long-term regret is going to be less, which goes back to the goals of care. If they’re involved in their decision and they made the choice that they’re very much bound to, this is a decision I made, this is part of my goals, this is part of my expectation. It’s not a decision you made for them, in which case, then it is your problem when it doesn’t work. It’s this whole psyche of medicine that we play a role in sometimes without realizing it. I think it is nice that we have differences in how the consensus statements are because we can use that sometimes to benefit the patient. It is difficult though because insurance doesn’t always actually buy either consensus statement or guidelines for that matter. It’s important to realize that oftentimes we might start with generic options first. A lot of times in a naive patient who comes to my clinic, I will talk to them about all the options but will tell them outright that most of the time insurance will prefer that you try 2 oral generics first. And if they’re willing to do that, we go that way first only because it will help with long-term insurance issues. I always like them to know though the reason I’m suggesting it is partly for insurance. And partly because sometimes for young women, it’s also important that it’s a pill I can start and stop though that is the beauty of the oral gepants prevention that we can stop it very quickly as well.

Transcript Edited for Clarity

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