Migraines
John Rothrock, MD discusses the difference between a headache and a migraine, as well as treatment options.
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Learn more about John Rothrock, MD
John Rothrock, MD
John Rothrock, MD is the Vice-Chair of the Department of Neurology and professor of neurology at The George Washington University School of Medicine & Health Sciences and is affiliated with The George Washington University Hospital. Dr. Rothrock received his medical degree from the University of Virginia and completed his internship and residency training in Neurology at the University of Arizona.Learn more about John Rothrock, MD
Transcription:
Dr. Mike Smith (Host): Welcome to The GW HealthCast. I'm Dr. Mike Smith, and today's topic is migraines. My guest is Dr. John Rothrock, he is the Vice-Chair of the Department of Neurology and is affiliated with The George Washington University Hospital. Dr. Rothrock, welcome to the show.
Dr. John Rothrock, MD (Guest): Thank you very much.
Dr. Smith: Awesome, so we're going to talk about migraines. I know this is a significant issue for a lot of people. I know some friends of mine that when they get an episode, some of them could be devastated by this, they can't even go to work, it actually interferes with their everyday life. So this is something that's I think an important topic, and I'm glad that you're on here. Why don't we do this first? Let's just first define what a migraine is.
Dr. Rothrock: I should start by saying first a migraine is a paradox. It's kind of the Rodney Dangerfield of medicine, it doesn't get much respect, and yet at the same time it arguably imposes more of a burden on the public health than any other neurologic disorder, and yet very few people - healthcare providers included - even know how to define it.
So it's very simple. The clinical definition of migraine is a 'yes' answer to the following question. Have you in your lifetime had five or more attacks of unprovoked headache, not the Cinco de Mayo death of tequila headache, but unprovoked headache that lasted four to seventy-two hours with severe enough to significantly inhibit your activities or even prohibit your routine activities and was accompanied by either nausea or light and sound sensitivity or some combination thereof? If the answer is 'yes,' you are one of the 12% of the American population that has active migraines.
Dr. Smith: Wow, 12%. That's a lot higher than I would have expected. Why do you think it is the- what did you call it? The Rodney Dangerfield of diagnoses in medicine? Why is that? How come we're not recognizing it?
Dr. Rothrock: The answer to that is very complex and probably multi-faceted and too complex to go into with a short answer, but suffice it to say that for reasons that are not entirely clear to me. Much less common disorders - say multiple sclerosis, myasthenia gravis, Duchenne's muscular dystrophy - receive far more attention than a disorder that is everywhere. You can't go to a cocktail party, you can't go to a ballgame without somebody wanting to tell you about their migraine. And if word leaks out that you as a healthcare provider have any interest whatsoever in headache, then you spend the rest of your life trying to hold back the deluge of headache patients and folks wanting to tell you about their headache, or their migraine in particular.
Dr. Smith: Yeah, so does this go for research as well? So you know, migraines don't receive the research funding that the other neurological disorders do?
Dr. Rothrock: That's been the case for a long time. It is changing, but it is true that still the vast majority of the money that goes into research in migraine and headache generally comes from the pharmaceutical industry. So there's relatively little government money or non-industry money devoted to migraine research. Much more now than there was before, but not as much. Things are changing. This week, within the next few days, the next great revolution in migraine will occur in migraine therapeutics. The first revolution was back in the late-eighties with the release of injectable Sumatriptan (Imitrex), the first designer drug for migraine- acute migraine treatment, FDA approved and released in 1991.
And in a few more days, either the seventeenth or eighteenth of May, the first of these CGRP antagonist class will be released - Amgen's product Aimovig - for use in preventing migraine, the designer drug for preventing migraines. So I've had the good luck to be serendipitously around with the first revolution, to assist with that, and now with the second as well.
Dr. Smith: Yeah, now for the prevention part of it, that's pretty good. I definitely want to come back to that, let's talk a little bit more about migraines themselves though. You gave a definition, right? And if you answered 'yes' to that- or you gave a question, and if you answer 'yes' to that question, you're part of that 12%. But how much variability is there within the migraine world of headaches? Meaning are there different types? Is there something that tends to be more common with people with migraines versus things that aren't so common?
Dr. Rothrock: Well I can tell you as myself, and having listened to the stories of tens of thousands of migraine patients, migraine is the Baskin Robbins of headache. I mean it ranges- the headache of migraine ranges all the way from no headache, you can have a migraine episode with aura only, let's say visual aura, to a commode hugging head-splitting incapacitating headache, and everything in between, including headaches that are indistinguishable from so-called tension type headache.
So the clinical phenotype of migraine, even on a given individual, ranges over a very wide range, and certainly does so from individual to individual.
Dr. Smith: Yeah, so in the 1980's a medication came out that allowed us to treat the acute migraine, and as you said that was revolutionary. But now we're entering into a different phase now, a different revolution if you will, which sounds like the world of prevention, which is always the key, right? Preventing disease is a much cheaper, easier way than actually treating something. So tell us about, as you said, what's coming up in maybe a couple days to prevent headache or migraine headache.
Dr. Rothrock: Well quite frankly, the patients are always interesting, but the stories that you hear are pretty much the same. Migraine diagnosis, you don't have to be a rocket scientist to be a migraine diagnostician or headache diagnostician. It's not very compelling or interesting to me, quite frankly, except the individual patients themselves. You know, neurology itself is fascinating. It's detective story one after another. But the migraine's not a particularly bewildering, or difficult, or complex diagnostic entity.
So what's cool about migraine is the research, and figuring out- part of the research is figuring out the circuitry that runs migraine, and we've done a good job of that in the last three decades, and now we have a very good idea of what biologically causes migraine, and now we're beginning to develop therapies to fit that circuit diagram, if you will. And the CGRP antagonists are highly selective, highly specific monoclonal antibodies that are directed against either a protein or a receptor to that protein that's integral to completing the migraine circuitry, and by targeting that one specific spot of the migraine circuitry, you can rheostat down the circuit and get a significant improvement in the migraine headache patient's burden.
That's what's really- that's what floats my boat. You know, you go to a headache clinic and you see ten or fifteen or twenty patients, and you may help those people hopefully, but you hope to develop a drug like Aimovig, a CGRP antagonist, and you help millions of people.
Dr. Smith: Yeah, so let's talk a little bit about the monoclonal antibody therapy, just so my audience really understands what's going on here. So there's a drug now that is an antibody that is able to bind to either a protein or a protein receptor that's important for that cascade that eventually ends up as a migraine headache. So far in the research, has this antibody which blocks that circuitry as you say, has this proven to be very effective in preventing migraines? What has the outcome been so far in the research?
Dr. Rothrock: Well I can only speak from my own seven years of experience with this particular antagonist, and some of the others as well as this antibody, but more important in my experience is what the FDA thinks. And the clinical trials data has shown this particular antibody, the Amgen product Aimovig to be very safe, very well-tolerated by patients, and very effective including effective in patients who have the most severe form of migraine which is chronic migraine, who have failed everything else including the best therapy we have for it. The only FDA treatment currently approved for treatment of chronic migraine specifically, and that's Botox. So we're suddenly now going to add a new therapy that wipes- Botox takes about 40% to 50% of the chronic migraine population and makes them headache-free or nearly so. Now we're going to add another hopefully 20% or 30% to that number and make further great inroads into the chronic migraine population.
So the general idea is you take a protein that you know is key to the circuitry of migraine, calcitonin gene-related peptide or protein, CGRP, and you find the receptor that likes to hit in the brain, or in the covering of the brain, the meninges, and you develop a mouse antibody to that receptor, and then you 'humanize' that antibody to make it less likely to trigger off the human's immune response - the patient’s immune response - and then you give it.
In the case of the Amgen product, you give it subcutaneously once a month. As the months go by, and the other company's products come to market, we'll also have an oral flavor that you take every day, a pill you take every day. From Allergan, we'll have a couple more subcutaneous products, and then one from Alder will have an intravenous product which you give every three months for migraine prevention. So it's really going to change the game and untether the patient from the provide, if you will, and empower the patients much in the same way that injectable Sumatriptan empowers the patient for treatment of acute headache.
Dr. Smith: I want to thank you for coming on the show today. You're listening to the GW Healthcast. Please visit GWDocs.com to get connected with Dr. Rothrock or another provider, or call 1-888-4GW-DOCS to schedule an in-person or virtual appointment.I'm Dr. Mike Smith, thanks for listening.
Dr. Mike Smith (Host): Welcome to The GW HealthCast. I'm Dr. Mike Smith, and today's topic is migraines. My guest is Dr. John Rothrock, he is the Vice-Chair of the Department of Neurology and is affiliated with The George Washington University Hospital. Dr. Rothrock, welcome to the show.
Dr. John Rothrock, MD (Guest): Thank you very much.
Dr. Smith: Awesome, so we're going to talk about migraines. I know this is a significant issue for a lot of people. I know some friends of mine that when they get an episode, some of them could be devastated by this, they can't even go to work, it actually interferes with their everyday life. So this is something that's I think an important topic, and I'm glad that you're on here. Why don't we do this first? Let's just first define what a migraine is.
Dr. Rothrock: I should start by saying first a migraine is a paradox. It's kind of the Rodney Dangerfield of medicine, it doesn't get much respect, and yet at the same time it arguably imposes more of a burden on the public health than any other neurologic disorder, and yet very few people - healthcare providers included - even know how to define it.
So it's very simple. The clinical definition of migraine is a 'yes' answer to the following question. Have you in your lifetime had five or more attacks of unprovoked headache, not the Cinco de Mayo death of tequila headache, but unprovoked headache that lasted four to seventy-two hours with severe enough to significantly inhibit your activities or even prohibit your routine activities and was accompanied by either nausea or light and sound sensitivity or some combination thereof? If the answer is 'yes,' you are one of the 12% of the American population that has active migraines.
Dr. Smith: Wow, 12%. That's a lot higher than I would have expected. Why do you think it is the- what did you call it? The Rodney Dangerfield of diagnoses in medicine? Why is that? How come we're not recognizing it?
Dr. Rothrock: The answer to that is very complex and probably multi-faceted and too complex to go into with a short answer, but suffice it to say that for reasons that are not entirely clear to me. Much less common disorders - say multiple sclerosis, myasthenia gravis, Duchenne's muscular dystrophy - receive far more attention than a disorder that is everywhere. You can't go to a cocktail party, you can't go to a ballgame without somebody wanting to tell you about their migraine. And if word leaks out that you as a healthcare provider have any interest whatsoever in headache, then you spend the rest of your life trying to hold back the deluge of headache patients and folks wanting to tell you about their headache, or their migraine in particular.
Dr. Smith: Yeah, so does this go for research as well? So you know, migraines don't receive the research funding that the other neurological disorders do?
Dr. Rothrock: That's been the case for a long time. It is changing, but it is true that still the vast majority of the money that goes into research in migraine and headache generally comes from the pharmaceutical industry. So there's relatively little government money or non-industry money devoted to migraine research. Much more now than there was before, but not as much. Things are changing. This week, within the next few days, the next great revolution in migraine will occur in migraine therapeutics. The first revolution was back in the late-eighties with the release of injectable Sumatriptan (Imitrex), the first designer drug for migraine- acute migraine treatment, FDA approved and released in 1991.
And in a few more days, either the seventeenth or eighteenth of May, the first of these CGRP antagonist class will be released - Amgen's product Aimovig - for use in preventing migraine, the designer drug for preventing migraines. So I've had the good luck to be serendipitously around with the first revolution, to assist with that, and now with the second as well.
Dr. Smith: Yeah, now for the prevention part of it, that's pretty good. I definitely want to come back to that, let's talk a little bit more about migraines themselves though. You gave a definition, right? And if you answered 'yes' to that- or you gave a question, and if you answer 'yes' to that question, you're part of that 12%. But how much variability is there within the migraine world of headaches? Meaning are there different types? Is there something that tends to be more common with people with migraines versus things that aren't so common?
Dr. Rothrock: Well I can tell you as myself, and having listened to the stories of tens of thousands of migraine patients, migraine is the Baskin Robbins of headache. I mean it ranges- the headache of migraine ranges all the way from no headache, you can have a migraine episode with aura only, let's say visual aura, to a commode hugging head-splitting incapacitating headache, and everything in between, including headaches that are indistinguishable from so-called tension type headache.
So the clinical phenotype of migraine, even on a given individual, ranges over a very wide range, and certainly does so from individual to individual.
Dr. Smith: Yeah, so in the 1980's a medication came out that allowed us to treat the acute migraine, and as you said that was revolutionary. But now we're entering into a different phase now, a different revolution if you will, which sounds like the world of prevention, which is always the key, right? Preventing disease is a much cheaper, easier way than actually treating something. So tell us about, as you said, what's coming up in maybe a couple days to prevent headache or migraine headache.
Dr. Rothrock: Well quite frankly, the patients are always interesting, but the stories that you hear are pretty much the same. Migraine diagnosis, you don't have to be a rocket scientist to be a migraine diagnostician or headache diagnostician. It's not very compelling or interesting to me, quite frankly, except the individual patients themselves. You know, neurology itself is fascinating. It's detective story one after another. But the migraine's not a particularly bewildering, or difficult, or complex diagnostic entity.
So what's cool about migraine is the research, and figuring out- part of the research is figuring out the circuitry that runs migraine, and we've done a good job of that in the last three decades, and now we have a very good idea of what biologically causes migraine, and now we're beginning to develop therapies to fit that circuit diagram, if you will. And the CGRP antagonists are highly selective, highly specific monoclonal antibodies that are directed against either a protein or a receptor to that protein that's integral to completing the migraine circuitry, and by targeting that one specific spot of the migraine circuitry, you can rheostat down the circuit and get a significant improvement in the migraine headache patient's burden.
That's what's really- that's what floats my boat. You know, you go to a headache clinic and you see ten or fifteen or twenty patients, and you may help those people hopefully, but you hope to develop a drug like Aimovig, a CGRP antagonist, and you help millions of people.
Dr. Smith: Yeah, so let's talk a little bit about the monoclonal antibody therapy, just so my audience really understands what's going on here. So there's a drug now that is an antibody that is able to bind to either a protein or a protein receptor that's important for that cascade that eventually ends up as a migraine headache. So far in the research, has this antibody which blocks that circuitry as you say, has this proven to be very effective in preventing migraines? What has the outcome been so far in the research?
Dr. Rothrock: Well I can only speak from my own seven years of experience with this particular antagonist, and some of the others as well as this antibody, but more important in my experience is what the FDA thinks. And the clinical trials data has shown this particular antibody, the Amgen product Aimovig to be very safe, very well-tolerated by patients, and very effective including effective in patients who have the most severe form of migraine which is chronic migraine, who have failed everything else including the best therapy we have for it. The only FDA treatment currently approved for treatment of chronic migraine specifically, and that's Botox. So we're suddenly now going to add a new therapy that wipes- Botox takes about 40% to 50% of the chronic migraine population and makes them headache-free or nearly so. Now we're going to add another hopefully 20% or 30% to that number and make further great inroads into the chronic migraine population.
So the general idea is you take a protein that you know is key to the circuitry of migraine, calcitonin gene-related peptide or protein, CGRP, and you find the receptor that likes to hit in the brain, or in the covering of the brain, the meninges, and you develop a mouse antibody to that receptor, and then you 'humanize' that antibody to make it less likely to trigger off the human's immune response - the patient’s immune response - and then you give it.
In the case of the Amgen product, you give it subcutaneously once a month. As the months go by, and the other company's products come to market, we'll also have an oral flavor that you take every day, a pill you take every day. From Allergan, we'll have a couple more subcutaneous products, and then one from Alder will have an intravenous product which you give every three months for migraine prevention. So it's really going to change the game and untether the patient from the provide, if you will, and empower the patients much in the same way that injectable Sumatriptan empowers the patient for treatment of acute headache.
Dr. Smith: I want to thank you for coming on the show today. You're listening to the GW Healthcast. Please visit GWDocs.com to get connected with Dr. Rothrock or another provider, or call 1-888-4GW-DOCS to schedule an in-person or virtual appointment.I'm Dr. Mike Smith, thanks for listening.