Preventive Treatments for Migraines - Episode 5
Peter Salgo, MD: What about migraine-specific medication treatment days? That’s a mouthful. Somebody define this for me. We’re going to be hearing this more as we go forward.
Shoshana Lipson: Sure. My understanding of that is—and it’s definitely a mouthful; I’m [on] a steep learning curve with these long terms that someone came up with. But my understanding is it’s the number of days you take 1 of 2 classes of medicine. That would be DHE [dihydroergotamine] or triptans which are acute treatments.
Stephen Silberstein, MD: Right.
Peter Salgo, MD: How’d she do?
Stephen Silberstein, MD: She’s perfect.
Shoshana Lipson: Thank you.
Peter Salgo, MD: Let’s talk about some studies. We’ve got the CHRONIC study, the fremanezumab study from AHS [American Headache Society] in 2018. What is the trial design? What are the results and the implications for this? And specifically the reduction in migraine-specific medication treatment days.
Stephen Silberstein, MD: I think there [are] 2 ways of looking at a clinical trial. Point 1 would be to get a trial that the FDA likes that makes your end point positive. So for example, in many trials, look at how many days a month you have migraine before and after treatment in the active drug and the placebo, and statisticians tell me that’s the most sensitive measure of showing a difference. But from the point of view of clinicians, it’s a bunch of baloney. I don’t really care…. Let’s say, for the sake of argument, you had patients who wound up with no headaches and patients with no change, the average would be halfway in between. What to me is more important is the individual response. What percentage of patients had a greater than 50% improvement? And in most of the studies of all the drugs, it’s round 50%.
Peter Salgo, MD: But 50% is huge.
Stephen Silberstein, MD: Correct.
Peter Salgo, MD: I mean, it’s a big number. We’ve seen drugs approved on 3% effectiveness—not necessarily in the migraine area but in lots of areas—3%, 4%, 5%, some of the oncolytics. So [at] 50%, these are good drugs and big results.
Stephen Silberstein, MD: That is correct.
Wayne N. Burton, MD: And we know that perhaps 25% of patients will have a more significant...
Stephen Silberstein, MD: Of the 50% responders, half of them have a 75% response.
Peter Salgo, MD: Even bigger.
Stephen Silberstein, MD: Yes.
Peter Salgo, MD: This is great news. The impact on the number of days of use. I think this is sort of bundled into this.
Stephen Silberstein, MD: [Fewer] headaches, less medication.
Peter Salgo, MD: [Fewer] headaches. Tell me about. This is almost too easy. I’m going to set this one up. It’s a softball coming right at you. The decrease in medication overuse headaches.
Stephen Silberstein, MD: Here’s what’s very important about that statement. Many years ago, 1 of the gospels in the headache world is [that] if you do not eliminate medication overuse, the patients won’t get better. But we’ve now shown with...topiramate and with the antibodies [that] it makes no difference. The patients do just as well whether or not they’re overusing medicines. And after they take a [preventive], medication overuse decreases.
Peter Salgo, MD: OK, I’m not following that precisely. In other words, if you can get a headache from medication overuse of the wrong drug, shouldn’t giving the patient a better drug or the right drug decrease that overuse headache? Did I miss this?
Stephen Silberstein, MD: It used to be. Let’s talk. What they’re overusing is an acute medicine.
Peter Salgo, MD: OK.
Stephen Silberstein, MD: What we do to stop it is to give them a [preventive] medicine. And for a long time in the field, there was a debate whether giving a [preventive] medicine would work if you still overuse it. And a lot of people would say stop it first and treat later. We now have clear evidence with many drugs that if you put them on a [preventive] medicine, most people will stop overusing because they don’t need it.
Peter Salgo, MD: The reason I got confused is that sounded so ridiculously obvious that I was surprised nobody thought of that.
Stephen Silberstein, MD: Well, it’s been a major debate between the Europeans and the Americans, and I’ve debated them. And the Americans believe treat first, stop later. The Europeans often believe detox first, medicate later. It’s philosophically different.
Peter Salgo, MD: Speaking as an American, I like our way better.
Stephen Silberstein, MD: So do I.
Peter Salgo, MD: It sounds rational. Now, you’ve got a little accent here. You’re from the other side of the pond. What makes sense to you?
Shoshana Lipson: Well, having been through the detox process over 10 years ago, I could say that as a patient, it is not a pleasant experience. I know from my group and my page that patients are really scared of going through what we know as the detox process. And so the concept that we can actually just go on a preventive that is effective without having to detox first is huge. The ramifications are enormous.
Peter Salgo, MD: And do these studies, whether it’s chronic or fremanezumab data, do they support 1 side or the other? What do the studies show?
Stephen Silberstein, MD: They all show that fremanezumab and the other antibodies work just as well with [or] without medication overuse.
Peter Salgo, MD: All right. Now, what are the implications for patients with migraine-specific medication day reductions? What is the implication in terms of [the] changes [to] how a patient lives?
Shoshana Lipson: Right. Well obviously, if you take a patient who’s having let’s say 20 to 25 migraine days or headache days a month, then they really don’t have a life, to be quite honest. They’re in bed a lot, they are probably unable to work or they are not working effectively, they don’t have a social life, they can’t attend their children’s school events, it can affect their marriages, and so much more. And it can increase the severity of the comorbid conditions that they have. So the implications of this are huge. The challenges that we’re seeing as patients—and we may be getting to this a little bit later, so forgive me—are just actually taking what is in the clinical trials and putting those into real-world use. And in terms of migraine, that is actually very challenging.
Peter Salgo, MD: And from a payer’s perspective, what’s your view on all this? How does this affect the amount of money you shell out?
Wayne N. Burton, MD: Well, from an employer’s standpoint, someone who is a migraineur has to take some time off work or they get a migraine at work—and many workplaces have quiet rooms for them—or they have to take time off work under the Family Medical Leave Act. So it could be paid or in some cases unpaid time. So it can have significant economic impacts, in terms of productivity, to [the] employer but also to the patient, to the employee.
Peter Salgo, MD: What does it mean in terms of actual out-of-pocket expense to a healthcare plan?
Maria Lopes, MD, MS: Well, the great hope is that we’re going to lower cost of care, right?
Stephen Silberstein, MD: We’ve done that.
Maria Lopes, MD, MS: Lower the totals of cost of care.
Stephen Silberstein, MD: We have done, in the past, 2 studies, 1 a generic study in a database looking at the total cost of care before the introduction of any [preventive], and we clearly showed a 50% reduction in total cost, doctor visits, ED [emergency department] visits, imaging. And we did the same thing for topiramate a number of years later and showed the same thing. So clearly, if you look at the analysis of total cost of care before or after prevention, it goes down.
Peter Salgo, MD: Of course it doesn’t necessarily follow [that] the costs go down if the cost of prevention is very high. If I have, let’s take a ridiculous example, a medication that costs a billion dollars a dose but reduces overuse—it reduces headaches by 99%. You’re not going to approve that. But it’s a great drug.
Maria Lopes, MD, MS: Well, I think we’re looking at what is the overall value. Even as payers, we now have ICER [Institute for Clinical and Economic Review] frameworks to look at value from different stakeholder perspectives. But certainly, if there [are] compelling data that [are] showing that you’re reducing, we usually like to understand the buckets and how quickly should the outpatient, the pharmacy, the inpatient—how quickly does that change. So the more data—and I would also argue for real-world because the CGRPs [calcitonin gene-related peptides] are a fairly new class of drugs—but the more we [data] have around [whether] this is the right patient, this is the right approach and be able to measure the impact with both the polypharmacy side, [these are] the wrong drugs, being able to get off opioids, but also measure the impact on ER [emergency department] visits and hospitalizations because that’s a big portion of total cost of care.
Peter Salgo, MD: So there’s a real advantage for an appropriately priced…
Maria Lopes, MD, MS: Yes.
Peter Salgo, MD: Preventive drug. Fair enough.