Emerging Therapies for Migraine - Making Sense of the Hype

Podcast Transcript

Alex Rae-Grant: Neuro Pathways, a Cleveland Clinic podcast for medical professionals exploring the latest research discoveries and clinical advances in the fields of neurology and neurosurgery. Welcome to another episode of Neuro pathways. I'm your host, Alex Rae-Grant, neurologist in Cleveland Clinic's Neurological Institute. In an effort to explore the latest advances in neurological practices, today we're going to talk about emerging therapies in the treatment of migraine headache. I'm very pleased to have Dr. Zubair Ahmed here with us. Dr. Ahmed is a staff neurologist and Director of Research in the section of headache and facial pain in Cleveland Clinic's Neurological Institute Center for Neurological Restoration. Zubair, welcome to Neuropathways.

Zubair Ahmed: Thank you for having me.

Alex Rae-Grant: I'd love for our listeners to get to know you a little better. Tell us just a bit about yourself - where are you from, where did you train and when did you begin your career at Cleveland Clinic?

Zubair Ahmed:  Well, I'm a Midwesterner through and through. I was born and raised in Chicago. I went to medical school in Milwaukee and did my training at the Cleveland Clinic starting in 2011.

Alex Rae-Grant: Let's dig into migraine headaches. Let's talk a bit about migraine in general. What is migraine and how common a problem is it? Does migraine interfere with how people function in life and work?

Zubair Ahmed:  Migraine is extremely common. As you know, it's one of the most common neurological disorders, seen not only by neurologists but primary care physicians, in the emergency department. I would say, according to current estimates, about 40 million Americans have migraine. It is considered the number one cause of disability in adult patients under the age of 50.

Alex Rae-Grant: Tell us a bit about the historical way that we've treated migraine, what have we done and how we approach that. Are there any limitations to that treatment? Why do we need better medicines, anyway, to treat migraine?

Zubair Ahmed:  That's a great question. Historically, for a long time, didn't know what was causing migraine. And so, we see accounts of people using trephination, you know, putting holes in patients' heads in order to treat migraine. More recently, we've used treatments like blood pressure medications, beta blockers in particular. We used anti-seizure medications as well as antidepressants to treat migraine. That's largely because we haven't had a specific preventative treatment just for migraine, so we've had to dip into other treatment modalities to try to determine if those also help with migraine.

Alex Rae-Grant: Wasn't that just good enough? Weren't we doing perfectly fine with migraine treatment before?

Zubair Ahmed:  You're right. Those medications all do help migraine. They all have class A or B evidence for the treatment of migraine. The reason why it's challenging is because many patients develop side effects to those treatments. That's evidenced by the fact that about 80% of patients within one year will discontinue their preventative for migraine. It really left us wanting a treatment that was not only effective but something that patients could also tolerate.

Alex Rae-Grant: Okay, so tell us about some of the newer medicines for migraine. What medicines are there and how do they work?

Zubair Ahmed:  The newer class of medications are referred to as CGRP monoclonal antibodies. These are antibodies to a molecule called CGRP, a neuropeptide. This neuropeptide is thought to be intimately related to migraine pathophysiology. And so these monoclonal antibodies, they go, they prevent this molecule from working in some situations. In other cases, they bind to the receptor where this ligand goes and exerts its effects. Patients in clinical trials had noted significant benefit. But more importantly, what we've seen is that patients have relatively few side effects with these treatments.

Alex Rae-Grant: Zubair, define for us non-migraine specialists what CGRP stands for?

Zubair Ahmed:  CGRP stands for calcitonin gene-related peptide.

Alex Rae-Grant: Do you think this is a game changer, this new class of medication? I mean, what do they provide over and above the older therapies? You mentioned side effects, but anything else that they provide?

Zubair Ahmed:  Yes and no. The clinical trials showed that not only did patients mention a reduction in headache frequency, but they also reported improvement in quality of life. Which is great, because at the end of the day, we're treating patients. We want to know that a treatment is not only reducing their number of headache days, but that patients are able to get back to work, they're not missing as much school. So all these other things are important as well. As you alluded to, we also noted that patients had fewer side effects while on this treatment. The most common side effect that they mentioned was either an injection site reaction. Some patients noted constipation in one of the trials. But many patients noted that they didn't have some of the other side effects, like cognitive problems or increased fatigue, compared to some of the other treatments that we currently use.

Alex Rae-Grant: Can we go a little more into detail about the specific CGRP inhibitor medications that are out there now?

Zubair Ahmed: There are three of these CGRP monoclonal antibodies — erenumab, fremanezumab, and galcanezumab. They're a mouthful. They've all been found to be effective, statistically significant to placebo in clinical trials. The clinical trials were done in patients who had both episodic migraine and chronic migraine.

Alex Rae-Grant: So you can use them in both classes of headache problem?

Zubair Ahmed:  Absolutely. In fact, the FDA indication does not specify whether they're limited to episodic or chronic. It just lists that these are preventatives for migraine.

Alex Rae-Grant: Are there any guidelines to how to use these medications or how to put them into practice?

Zubair Ahmed:  The American Headache Society at their recent meeting, as well as in a position paper that was published earlier this year, mentioned that for patients who are doing well on a current therapy, even if it's not a CGRP monoclonal antibody, it's okay to continue them on that therapy as long as they're tolerating it well. They haven't noticed any major side effects. For patients who have failed two or more preventatives, traditionally used preventatives, then the CGRP monoclonal antibodies may be a good option for those patients.

Alex Rae-Grant: What kinds of things should providers know about these new medicines? You know, how to prescribe them, how to monitor them, side effects to tell their patient population about. What kind of things should they know?

Zubair Ahmed: The first thing I think that's very important is that migraine treatment revolves around more than just medications. It involves improving patients' sleep, improving their diet, avoiding triggers when possible, as well as medications. It's very similar to the way we treat other chronic medical conditions like high blood pressure or hypertension. If we just give patients a medication but don't limit their salt intake, for example, or change the way that their lifestyle is in terms of from a sedentary lifestyle to a more active lifestyle, then it often becomes challenging to treat high blood pressure. Migraine is very similar in that way, where we want patients to become more active. We want to improve their sleep. Again, we want to limit their triggers, knowing that those things can certainly trigger headaches and be involved in the frequency of headaches, especially migraine. And so the medications are an aid to a multidisciplinary approach, which includes diet and sleep and hydration and these other things.

Alex Rae-Grant: Is there any component to emotional health that you guys think about in the headache center?

Zubair Ahmed:  Absolutely. In some patients, because migraine tends to be a genetic condition — it has a genetic predisposition — as well as environmental triggers, we think that emotional health is really, really important. There are some things that we just can't account for, right? Life is filled with stressors and it's often challenging to deal with those stressors. The headache disorder itself, migraine in particular, can be extremely stressful on an individual, because they may not be able to predict exactly when their next headache is going to occur. Knowing those types of strategies and what to do, especially because the migraine is so unexpected, can be really important in managing the migraine effectively.

Alex Rae-Grant: Let's come back to the newer medicines for a moment. What about the cost of medicine? What can you say about that?

Zubair Ahmed:  Well, these medications are expensive. There's no two ways about it. They cost about $575 per month, which can be very challenging for most patients to afford. What we've seen in our clinical practice, though, thus far is that most insurers are approving the treatment if the patient is a good candidate. Right? If a patient has failed two or more other preventatives, if a patient has failed onabotulinumtoxin, for example, the insurers are covering the cost of most of these medications. The co-pays are reasonable, and most patients are able to pay the co-pay.

Alex Rae-Grant: Have you in your practice seen anybody who has had a bit of a life-changing experience with newer medication? Has it had a major impact on anybody you can think of specifically?

Zubair Ahmed:  Absolutely. Several patients come to mind. In particular, there was a young woman who was a medical student, who had gone through a very traumatic life experience. I would have to say that she had tried at least six or seven different preventatives at adequate doses and had not noticed an improvement. She was anxious, because she was starting residency which, again, is associated with significant stressors. We placed her on a CGRP monoclonal antibody, and she's done remarkably well. I previously had checked in with her about once a month, either through a message or through a clinic appointment in person. But since she's started it, she's mentioned that she's able to exercise. It's really turned her life around. Now, I think there are patients on both ends of the spectrum. There are some patients that will respond extremely well. The clinical trials show that, that there were some patients who "were super responders," that did really well with the treatment. Then, there are those patients that we certainly see, also, who don't have any improvement with their headaches. Everybody else kind of lies in the middle. These treatments can be effective in the right patient.

Alex Rae-Grant: Zubair, any other headache management techniques that your group is using at the Cleveland Clinic?

Zubair Ahmed:  Yes. We have an online headache education program, formally referred to as V-MATCH, or the virtual method for the assessment and treatment of chronic migraine. It's an eight-week program in which patients, through an online platform, learn more about migraine. They learn about what causes the disorder. They learn about common medications that are used. In addition, they have a visit every week for eight weeks. That allows them to get a better understanding of what migraine is and how they can treat it.

Alex Rae-Grant:Just to finish up, is there anything else that you'd want to tell a general neurological audience about treating migraine, something you've learned in your practice that would really help them caring for their patients?

Zubair Ahmed:  Many of our patients, they have chronic migraine, defined as more than 15 headache days per month, of which eight are at least migraine. These patients, they are really looking for a treatment that can be both beneficial for them and that's not associated with side effects. A lot of patients have failed several other preventatives, so they're really looking, oftentimes, for a cure for migraine. I just want to emphasize that although these treatments are one step in the right direction, we don't quite have a cure yet. Some patients can come with the unrealistic expectation that these medications are going to solve all their problems. While that may be true in a small subset of patients, again, migraine is a very complicated disorder that requires treatment in multiple different modalities, of which medication is one.

Alex Rae-Grant: Okay. Well, thank you, Zubair. Thanks so much for joining us. I really appreciated your time and insights.

Zubair Ahmed:  Thank you. It was a pleasure being here.

Alex Rae-Grant: This concludes this episode of our Neuro Pathways podcast. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast. Subscribe to the Neuro Pathways podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you get your podcasts. Don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website, consultqd.clevelandclinic.org/neuro, or follow us on Twitter at CleClinicMD. All one word. That's at C-L-E Clinic M-D on Twitter. Thank you for listening. Please join us again soon.