Video

The Role of Developing Agents in Acute Migraine Paradigm

Experts in the management of acute migraine consider how the various emerging agents are being used in clinical practice and discuss upcoming studies that are defining the future of treatment.

Wade M. Cooper, DO: When I take a step back and look at what these new tools have offered us, we know that patients with migraine have an unmet need. We know some of them don’t have the right diagnosis; we know those people with migraine who do have the right diagnosis don’t always have reliable treatments available to them. In the last year, we’ve seen 3 different medicines FDA approved for acute therapy.

That includes 2 as-needed medications that work on CGRP [calcitonin gene-related peptide] blockade, it includes 1 brand new class of medicine called lasmiditan, as well as the promise for certain prevention therapies for once a day dosing for the CGRP medications. What’s fantastic about this is our patients who didn’t have a lot of good options for their acute migraine, even just 8 or 9 months ago, now have multiple options that could be really effective for them. And at our practice we’ve used all 3 of these agents extensively; we’ve seen nothing but good results. We know that the CGRP small molecules are well-tolerated, quite effective for some, including those who don’t respond to triptans. We know lasmiditan has some adverse effect issues attached to it, remember, it has an 8-hour no driving restriction after you’ve used the medication, but it has some really impressive efficacy that has saved the day for a lot of our patients with migraine. Hopefully, after watching our presentation, you are going to be able to apply these to your clinical practice and change the lives of people with migraine.

When we talk about what the future holds, there are lots of things to be excited about. We’re starting to understand this inflammatory cascade better, and there are a few exciting inflammatory peptides that could be further targets for us. We also know there’s a hormonal component in regulating the autonomics of migraine, meaning blood vessel dilation and constriction, eyeball watering, or nasal stuffiness, so targeting the hormone control of this central activating pathway might yield really good results. I’m excited to see what we can come up with, with acute therapies and prevention therapies that target these avenues.

On top of that, one of the things we’re missing right now is long-term safety studies on these CGRP medications. Our experience so far with monoclonal antibodies, the once a month or once every 3 month dosing to prevent migraine, has been phenomenal from an efficacy standpoint. It has also shown some adverse effects that weren’t available and weren’t known about in the initial clinical trials.

We know that erenumab had to add on constipation and add on increased blood pressure shortly after starting the medication. And we don’t know what else it’s going to show in 5, 10, 15 years down the road, so those are the things I’m looking to see. So far, I don’t expect anything major coming out of those, but those are the things that will give me confidence when I prescribe those medications to young people who might need them for many years to come.

Amaal J. Starling, MD: It’s such an exciting time for migraine management. We really have an explosion of therapeutics, and it seems like every 6 months there are new treatment options clinically available for our patients. Our toolbox continues to expand, and that is great. That is great for patients, and that is great for health care providers so that we can continue to explore every single treatment option until we find the right one for our patients. For the acute treatment of migraine, at this point, without having a way of individualized, personalized treatment, I dream about being able to take the blood or saliva sample from my patient and it will tell me which migraine treatment option is going to work, which one is not, and which one is going to give them adverse effects. 

Without that, right now, I have a bunch of clinical trials, and I have guidelines from the American Headache Society and the American Academy of Neurology. Based on what I have available now, the patient who comes to me with migraine, based on their medical comorbidities and if they don’t have contraindications, I will start with triptan medications. If they have nausea and vomiting, I will likely explore different formulations like nasal formulations or injection therapies.

If they have contraindications, or if triptans are ineffective or cause adverse effects, I will likely try other options like lasmiditan because it is a 5-HT1F agonist and it does not have any effect on blood vessels, which is a very attractive option for anyone who has cerebrovascular disease, cardiovascular disease, or has a good response to triptans from a pain relief perspective but has adverse effects from triptans that they don’t tolerate. Those are individuals for whom lasmiditan might be a great option, or we have gepants, like rimegepant or ubrogepant, which might be great options. Then we also have devices such as a supraorbital neurostimulation device. We have an arm stimulation device. A lot of these devices could also be acute treatment options for our patients.

There are also many trials ongoing that are exciting in the space of migraine. Some of these are in the device realm. Some of these are still in the CGRP small molecule agonist realm. One of them is looking at the medication rimegepant to see if it might be effective for prevention. The reason I think that is a very interesting trial, and how it can impact the acute treatment of migraine, is this might end up being a medication that we can prescribe for patients as needed. But if they need to use it too frequently, it ends up working as a preventive agent. Then when they’re not having to use it as frequently, it works as an as-needed medication. I feel like that is something patients probably have been seeking for many years, and it may be something that we’ll be able to provide patients in the future. I’m looking forward to seeing those data and that FDA approval in the future for prevention, if possible, and definitely looking forward to other gepant small molecule, CGRP antagonists to become approved for acute therapies.

Wade M. Cooper, DO: When we talk to general neurology colleagues, we know that many times, there’s not an interest to help people with migraine. People with migraine previously had a lot of needs, and a lot of unmet needs. Before now, we just didn’t have the tools to help people, but now we’ve got good prevention therapy, studies for migraine prevention that look really effective with minimal adverse effects, and easy to use prevention therapies that can change people’s lives. On top of that, we’ve got really good, brand new acute therapies, some with minimal adverse effects, some with phenomenal efficacy, and we’ve got to use these tools to help patients in need. So for those who are watching this, make sure you appreciate the new tools out there and start changing the world for people with migraine.


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