Migraine Therapies for Both Acute and Preventive Treatment

Stephanie J. Nahas, MD, MSEd; Anna Pace, MD


October 04, 2021

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This transcript has been edited for clarity.

Stephanie J. Nahas, MD, MSEd: Hi. My name is Dr Stephanie J. Nahas. I'm an associate professor in the Department of Neurology at Thomas Jefferson University, where I also direct the Headache Medicine Fellowship Program at the Jefferson Headache Center.

I am pleased to be here with you today, along with my esteemed colleague, Dr Anna Pace, to talk to you about the dual roles of some treatment in migraine, which can serve as both acute and preventive treatments. Dr Pace, would you like to introduce yourself?

Anna Pace, MD: Sure. My name is Dr Anna Pace. I'm an assistant professor of neurology and a headache medicine specialist at the Icahn School of Medicine at Mount Sinai in New York.

Nahas: Dr Pace, this isn't really that new of an idea, is it — having some treatment that can work both acutely during a migraine attack and to prevent headaches from coming back? For decades, if not centuries, people commonly have taken analgesics to treat an attack and then to prevent it from coming back. Sometimes they wind up taking something every day and they might get into rebound headache, but for some people, this actually works. Would you agree with that ascertainment?

Pace: Yes, absolutely. I think it's especially relevant for our patients who have menstrually related migraines where they may be using nonsteroidal anti-inflammatory medications (NSAIDs) or even the triptans preventively or as, essentially, a mini-prophylaxis during their menstrual cycle, where they may be taking NSAIDs twice a day for 3-5 days, starting before their period and then throughout the period.

The same goes for triptans like naratriptan and frovatriptan, where they may also be taking it twice a day. Separately from the headaches around their menstrual cycle, they may be taking those triptans acutely for other headaches in the setting of weather changes or lack of sleep and so on.

Nahas: Indeed, as we've kind of come into more of the modern era of headache medicine, these kinds of things have actually been studied not only with menstrually related migraine but with other anticipated triggers, such as fasting or alcohol. Using NSAIDs on a daily basis for some people has some scientific basis, although we don't do it often, do we?

Pace: Not particularly. I think there's always a concern about medication overuse or rebound headaches when patients are utilizing the NSAIDs too frequently. That may play into adjusting the treatment regimen to focus on preventive therapies while still allowing the patients to use the NSAIDs for acute therapy.

I do find that, especially with patients who have very specific triggers and we anticipate the triggers happening — some of my patients who are teachers who may be going back to school and know that those first couple of days are particularly difficult — we may do a mini-prophylaxis ahead of time and use those acute therapies preventively.

Nahas: As we've gone through the passage of time and as we come into more of the current era of the treatment landscape, there's a particular class of treatments that's really been at the forefront of this dual nature of treatment, something you can use during an attack on the spot and every day for prevention over time. What comes to mind first are the neurostimulators.

Pace: Yeah, there are so many neuromodulation devices that have been cleared by the US Food and Drug Administration (FDA) for the acute treatment and preventive treatment of migraine, as well as one, in particular, for the prevention of cluster headache.

One of the more common ones that I see being used is the external trigeminal nerve stimulator (Cefaly Dual; Cefaly Technology), a supraorbital transcutaneous neurostimulator. It has an acute mode and a preventive mode. Patients can use the device (placed over the forehead) in acute mode during an actual migraine attack and it runs for a longer period of time (60 minutes) than in the preventive mode, which they would be using every single day (for 20 minutes) in an effort to prevent the headaches from coming.

Most of my patients clinically find these devices to be very useful, and I think it also is a great option for patients who are hesitant to take prescription medications or they have other contraindications to certain medications. This includes special populations, such as patients who are elderly or who have many other medical comorbidities, for whom certain other acute therapies or preventive therapies may be difficult to use given other medications they may be taking.

These devices, I think, really have paved the way for many treatment options for these patients and they also play a dual role. It's nice to have one option that could be used for two things. Patients really enjoy having the ability to have one thing that can be used acutely and preventively.

Nahas: Now, you mentioned specifically this supraorbital transcutaneous neurostimulator, but there are two others used in migraine that you touched on. One is the noninvasive handheld vagus nerve stimulator (gammaCore; electroCore, Inc.) and one that's a little bit different, a single-pulse transcranial magnetic stimulator (sTMS mini; eNeura, Inc.). Could you tell us a little bit about each of those?

Pace: Sure. The noninvasive vagus nerve stimulator was originally FDA-cleared for the acute treatment of migraine and the preventive treatment of cluster headache, and then later on, with further trials, was FDA-cleared for the preventive treatment of migraine. The way that one works is, essentially, by modulating the function of the vagus nerve and modulating the perception of pain. (When placed over the vagus nerve in the neck, the device stimulates the nerve, resulting in reduced activity in neural pathways linked to migraine.) The nice thing about this is that it's noninvasive, so it does not require surgery. In the past, other studies have shown that surgical interventions may have similar results.

The single-pulse transcranial magnetic stimulator was originally cleared by the FDA for the treatment of acute migraine with aura, and many of my patients with aura have found this device to be very helpful. Later on, it was used for patients with and without aura, as well as for the preventive indication for migraine with and without aura.

It's a device that, after pressing the power button, creates the stimulus used to try to stop an aura and a migraine attack from happening (when the device is positioned so it cradles the back of the skull). And using it preventively helps reduce the frequency of attacks.

Nahas: It's really interesting how these devices with different mechanisms are trying to talk to the brain and to calm it down through peripheral inputs in the case of the external trigeminal stimulator and the vagus nerve stimulator.

This single-pulse transcranial magnetic stimulator is cool, too. I like to think of it as something that is taking this gelatinous brain and solidifying it a little bit more so it's not quite so bouncy. I don't know if you like to think of these sorts of analogies for how these devices might work, but that's how I describe them to my patients. How do you describe them?

Pace: I really like that analogy. I've never heard that one before, but I do like it. The way I describe these devices… I'm the kind of person who likes to keep a number of different tabs open on my computer. Sometimes when you open that last one, you get the spinning wheel on your computer and it doesn't work as well.

The way I describe migraine to patients sometimes is that it's as if there's a constant feedback of so many tabs open at the same time. One of the ways in which you can help reset your computer or your system is by using some of these neuromodulation devices, whereby any of the electrical stimulations they produce are essentially resetting the system and disrupting the feedback loop so it's not constantly spinning and, therefore, not actually functioning the way it should be.

Nahas: Well, that's a really cool one that is near and dear to my heart because I am notorious for having way too many tabs open at all times. With your permission, I'm going to steal that one and add it to my bank of analogies.

Pace: Absolutely.

Nahas: Let's get into what I think everybody came to hear about, which is the most recently approved pharmacologic treatment for both the acute treatment of attacks and prevention of migraine, reducing it over time. That, of course, is rimegepant.

Pace: Yes. Rimegepant is one of the CGRP receptor antagonists. It's an oral medication, so it is different from the CGRP monoclonal antibodies, which have gotten a lot of press over the past 3-4 years or so. Rimegepant was originally approved for the acute treatment of migraine when taken as needed. The studies essentially found with rimegepant that a number of patients achieved pain freedom (21% vs 11% on placebo) as well as freedom from most bothersome symptoms at 2 hours (35% vs 27% on placebo). These patients also continued to have relief 48 hours later. This was a great, acute therapy that was available for patients.

I find that it's particularly useful for patients who have a higher likelihood of recurrence or where their headaches and their nausea or photophobia start and continue to linger despite having a little bit of improvement in their headaches or other pain with a triptan, for example.

Later on, rimegepant was approved for the prevention of migraine when dosed every other day. One multicenter, phase 2/3, placebo-controlled study looked at 348 patients taking rimegepant vs 347 patients allocated placebo every other day for 12 weeks. The primary efficacy endpoint was the change from baseline in the mean number of migraine days per month. They found that the patients on rimegepant had significant improvement in their headache frequency (-4.3 days vs -3.5 days with placebo), with very minimal side effects compared with some of the traditional preventive therapies that we currently use. I don't know if you would agree with some of the study findings clinically in your practice and how you've been using rimegepant.

Nahas: Indeed. We've seen, like anything, mixed results with these treatments, but I think that they've exceeded expectations in some circumstances. I've had some patients who didn't respond very well to anything, and yet they find the gepants, and particularly rimegepant, to be useful acutely. It's also useful for those patients who don't have chronic migraine but who have episodic migraine and they run into trouble.

I'm thinking of a particular patient I saw yesterday who had been doing very well with about one migraine attack per month. I gave her rimegepant last year to try as a new acute agent and she loved it.

I spoke to her yesterday. She's running into trouble at work. There are a lot of changes with staffing, sites are closing, her workload is skyrocketing, and her schedule is becoming crazy. She might only have 12 hours in between shifts and she's already starting to see her attacks dial up. She was really excited to hear that she could potentially have more rimegepant available to her on a monthly basis and she can take it every other day for as long as she's in this situation, when her migraine is being stirred up, when work is poking the hornet's nest, as it were.

Before she really gets into trouble — this just started a few weeks ago and she's got a history of chronic migraine and medication overuse or rebound headache, and she's really worried about what could happen — I'm really hoping that in a few months she's going to say, "This was a perfect strategy to get me through this phase. I took it every other day. I still had one or two left over if I needed it, and now I feel like I'm in a better place and I might not need to take it every other day anymore and I can go back to once-in-a-while use."

It may be a niche product and a lot of us had a little bit of difficulty envisioning where and when it would fit in, and how somebody's going to remember to take it every other day. I guarantee you that you should keep your ears out and your antennae up for patients like this. This is just one example.

Dr Pace, I'm sure you can think of some other examples where you found a particular scenario where alternate-day dosing of an acute medication that works for the patient can be a long-term solution.

Pace: Yes. Actually, although this isn't necessarily on the label, I have found that rimegepant is very useful for patients who have menstrually related migraine or they're more prone to status migrainosus, where the headaches continue to linger around that time. Separately from their menstrual cycle, they're still having a good number of migraine attacks prior to or afterwards.

Being able to utilize rimegepant every other day, especially during that time, also has been allowing them to use fewer triptans, NSAIDs, and other acute therapies, and actually giving them more sustained relief so they don't feel like they're constantly out of commission for a week at a time each month.

I've also found rimegepant to be really useful for my patients who have higher-frequency migraine with aura, whether or not entirely chronic, but they're right at the cusp where certain other preventive therapies may not necessarily be available to them at the time. I do think that taking rimegepant every other day is a little bit cumbersome. For most of my patients, I do try to tell them to set an alarm on their phone to remind them to take it. For the most part, once they find that it's working really well, it's very easy for them to remember to take it. If they don't, then occasionally headaches may recur.

Nahas: Exactly. If their phone doesn't remind them, probably their migraine will remind them to take it.

Pace: For sure. Absolutely. I think it really has been filling a gap, especially for patients who have tried triptans and have not been able to get sustained relief, with headaches recurring, or they're having side effects from the triptans. Rimegepant was a really nice and welcome second option in the acute therapy realm, and now adding an extra bonus to having a preventive indication has been really useful for a number of patients. I'm looking forward to seeing how this pans out and whether there are other subpopulations of patients that we find later on that could also benefit.

Nahas: Indeed, it's been a really exciting time to practice headache medicine for a number of years. It seems like for the past 10 or 12 years, there's something new every year to look forward to. It's a great time to be alive and to practice headache medicine, and it's become more and more fun. I hope you would agree with that assessment.

Pace: Absolutely. Also, it's been nice to be able to give some patients more hope. I think over time, many patients have felt, "Well, I've tried so many different medications and there aren't any left." Now, as each year passes, newer, more targeted therapies have been available for patients. We now have the opportunity to say, "Actually, there are still more medications that you have not tried," with a higher likelihood of these patients actually having success and relief with these drugs because they are targeted to the migraine pathophysiology, when in the past we didn't have those available.

Nahas: Exactly. I think that because much study and inquiry has been going into pathophysiologic-specific treatments, that's why we're starting to see that some of these treatments can serve both purposes. This line between acute and preventive is becoming blurrier and blurrier where we're in this whole new world. It's like the globe is spinning. Which are we doing? Is it prevention? Is it acute? You know what? It's just migraine treatment.

Pace: Yes, exactly. Agreed.

Nahas: I think that's about all the time we have for today. Thank you all for joining us. Once again, I'm Dr Stephanie J. Nahas, associate professor in the Department of Neurology at Thomas Jefferson University in Philadelphia, Pennsylvania. I've been joined by…

Pace: Dr Anna Pace, an assistant professor of neurology and a headache medicine specialist at the Icahn School of Medicine at Mount Sinai in New York City.

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