Patient Selection of Novel Therapies for Migraine Treatment
EP: 1.Unmet Needs in the Management of Migraine
EP: 2.Acute Treatment of Migraine: Traditional Therapies
EP: 3.Evolution of Acute Treatment of Migraine
EP: 4.Acute Treatment of Migraine: Progress With Novel Medications
EP: 5.Use of 5-HT1F Agonists in Acute Treatment of Migraine
EP: 6.Safety of CGRP Receptor Antagonists vs 5-HT1F Agonists
EP: 7.Intranasal DHE in Acute Treatment of Migraine
EP: 8.Patient Selection of Novel Therapies for Migraine Treatment
EP: 9.Role of Neuromodulation for Acute Treatment of Migraine
EP: 10.Patient Selection for Neuromodulation Devices
EP: 11.Behavioral and Lifestyle Strategies for Migraine Management
The role of novel therapies in transforming the acute treatment of patients with migraine.
Peter J. Goadsby, MD, PhD: When we think about these novel things that we’ve discussed—the ditans, the gepants, and the new formulations of DHE—are there particular patients who you think might benefit from 1 or the other, Wade? Are there people who walk in and you think, “I’ve got news for you”?
Wade M. Cooper, DO: It changes the conversation. Now I can confidently ask about their triptan experience and respond to what they’re telling me. If someone says, “It doesn’t work all the time, and I just feel like it’s helpful,” most of the time, they won’t want to give up their triptan therapy, but they’re hungry for something that’s effective and not going to give them adverse effects. They want some faith that if they have an acute headache, they’re not going to lose the day.
What is most problematic to our patients are these gaps in their lives that are robbed by the demon of migraine. Generally, if someone comes in and you ask about their triptan or their other acute therapy, and they say, “I don’t like taking it. It makes me feel sick or funny,” I’m thinking gepants in that type of situation. Someone comes in and says, “I use it, and it seems like it helps, but it just doesn’t have the power I’m looking for. I lose time from my family and from my life.” They’re still remarkably ill.
Even if the triptan is effective 50% of the time, that’s still half the time that it’s not effective. That’s where I tend to go to the lasmiditan. Fair or not, I have pigeonholed it that way. Lasmiditan, based on clinical trials, showed efficacy that rivaled sumatriptan, and perhaps bested it in a few spots. Compare that with the gepants, whose adverse-effect profile was their heralding call. That’s where I am with those medications.
Peter J. Goadsby, MD, PhD: There’s a mechanistic basis for people to think about DHE, because you get all the serotonin receptors, plus you pick up some adrenergic receptors that are probably important in process. It’s the price you pay, isn’t it? The more specific something is, the fewer mechanisms it interferes with, the fewer adverse effects you’ll get, and the smaller the group that responds.
The messier a drug is, the more people who will respond, you’ll find more adverse effects, and the more who might want to use it. I think of amitriptyline like that—noradrenergic, serotonergic, dopamine reuptake. It’s a messy drug, but it has some utility. Topiramate is like brain Drano. It affects practically every pathway you can think of. Patients respond, but they can barely remember what the response was because of the broad adverse effect.
It’s inevitably what we do. We home in on specific targets. Tolerability is great, but the range of people who respond to this is interesting. It’s an interesting balancing that we do. Jelena, do you have people who stand out for you? Are there those who, when they walk in, you say, “I’ve got some news for you”?
Jelena Pavlovic, MD, PhD: I have 1 general response to your comments, which I completely agree with. That’s precision medicine, right? Precision medicine often requires a lot of precision, and a cost comes with that. It takes a lot of time and these evolving stories from our patients. We may give them 1 medication. They may have a response.
What I try to teach our fellows is that the response to medication is also informative. You get a sense of, is this GABAergic tone, glutaminergic tone, or CGRP?
I fully agree with everything that Wade said. I would add that because of the ODT [orally disintegrating tablet] formulation we spoke about earlier of rimegepant, I consider it for those who have very quick onset of headache. The headache increases in severity quickly, and if they treat 30 to 45 minutes later, it’s hard to pull back and get relief. That is my first choice in those headache cases.
Paul G. Mathew, MD: Peter, I’d like to share 2 things that I found very surprising. When these new classes of medications came out, we all envisioned our patients who complain about adverse effects or people who find them inconsistently effective. What I didn’t think we would see in clinical practice, and I see it all the time, is that when you probe these patients who have told you it works and they don’t have any adverse effects, these are the people who are taking a second dose frequently or having adverse effects that they don’t talk about.
I’ll be bold and say that in a few years, we’re going to see a shift, in which 60% to 70% of our patients are on ditans or gepants and only 20% to 30% are truly happy with their triptans, in terms of not having adverse effects and finding them effective. The other thing that surprised me, and you certainly can comment if you had similar experiences, is how many people have taken a CGRP antibody and found it ineffective after taking it for 3 or 4 months. Then you put them on abortive therapy and they surprisingly work well.
I don’t have a good explanation for it, but that’s been a big surprise for me in clinical practice since the advent of the gepants.
Peter J. Goadsby, MD, PhD: It’s beyond irritating, isn’t it? The book would suggest that if a monoclonal antibody didn’t work, targeting the receptor ought to not work either, but the problem is that we haven’t written the right chapters in the book yet.
Paul G. Mathew, MD: The only thing I can think of is, if you have an antibody that suppresses the overall level of CGRP, does the system or the body have some kind of compensatory mechanism? If you’re suppressing episodically with a gepant, does that compensatory response not happen? That’s 1 thing I can think of, but that’s only speculation.
Peter J. Goadsby, MD, PhD: I haven’t given up on the central nervous system as a possibility. The gepant access to the central nervous system is better than monoclonal antibody access. The idea that everyone has the same problem with migraine and that it’s all centered on 1 structure doesn’t make any sense if you look at the complexity of the network disorder.
The problem we have is not that we have wonderful tools. We have wonderful tools, but it’s always been and continues to be a question of how you pick the patient to put the tool in. We do this alchemy business, but I much prefer to ultimately be able to say to a patient, “This will fit for you because of X.” That’s going to be 1 of our great challenges going forward.
Paul G. Mathew, MD: That really punctuates the point that migraine is actually a massive umbrella term that contains so many subtypes. Some people are successful with the beta-blockers. Some people are more CGRP based. As you said, the Holy Grail, which we all look forward to, is that someone comes in with a diagnosis of migraine, we do a blood test, and we’ll be able to genetically subtype them and then refer them to the appropriate therapy. But that’s many moons away.
Peter J. Goadsby, MD, PhD: In the meantime, we have headache medicine doctors to struggle with the details. Thank you for that.
