Dual Migraine Treatment Is Supported As Safe and Promising
A recent study published in Headache: The Journal of Head and Face Pain, Safety and tolerability of ubrogepant for the acute treatment of migraine in participants taking atogepant for the preventive treatment of episodic migraine: Results from the TANDEM study, provides information on the safety and tolerability of combining ubrogepant (acute treatment) with atogepant (preventive treatment) for patients with episodic migraine.
As Dr. Jessica Ailani, the study's lead author, noted in a recent interview: "The first thing that was really interesting that we didn't think through was, once you put a patient on prevention (in our mind, this was still early days of anti-CGRP)... you still need an acute treatment because you're going to have migraine attacks. Well, actually, a big portion of patients, once they started atogepant, had a pretty big drop in migraine frequency."
Watch the whole discussion with Dr. Ailani:
Headache publishes original articles covering all aspects of head and face pain, including clinical and basic research, diagnostic and treatment, epidemiology, genetics, and the pathophysiology of both primary and secondary headaches, cranial neuralgias, and referred pain in the head and face.
Migraine is "a complex neurological disease, and personalized management may require the use of both acute and preventive treatments." This study represents an essential step in advancing migraine care by evaluating the safety of using atogepant and ubrogepant together. As the first clinical trial to explore this combination, it provides valuable insights for clinicians seeking to improve treatment strategies. While the results support that the dual approach is generally well tolerated, further research is needed to understand its long-term effects and refine best practices in headache medicine.
The TANDEM study represents a significant advancement in understanding combination therapy for migraine, offering valuable reassurance to clinicians navigating treatment decisions. Confirming the safety of atogepant and ubrogepant addresses a critical gap in migraine management and provides a foundation for more personalized, effective care. This study also reflects a more significant shift in the field, where treatment strategies are increasingly tailored to individual patient needs.
As migraine treatment continues to evolve, research like this plays an important role in refining best practices, guiding clinical decision-making, and ensuring that emerging therapies meet the highest safety and efficacy standards. While these findings mark essential progress, they also highlight the need for continued investigation into long-term outcomes, particularly for patients who use acute treatments frequently. Understanding how combination therapy fits into the broader migraine treatment paradigm will be key to optimizing care for the millions affected by this complex neurological disease.
Patients generally tolerated the combination therapy well, with no increase in adverse effects. Common side effects included COVID-19 (8.4%), fatigue (6.5%), nausea (6.1%), decreased appetite (5.7%), and constipation (5.3%), but no new safety concerns emerged. Despite some side effects, the study shows that only 9.9% of participants discontinued treatment, and no serious safety signals were identified.
This study provides strong evidence that atogepant and ubrogepant can be safely used together for episodic migraine management, when ubrogepant use is limited to 10 days per month or less.
"It is safe to use a combination," Dr. Ailani said. "This is the one combination we've studied, atogepant 60 mg and ubrogepant 100 mg, and patients could take a repeat dose if needed…There were no added increased safety risks or concerns."
Read the Interview Transcript
Dr. Rashmi Hawker Singh
I'm Dr. Rashmi Hawker Singh. I'm the deputy editor of Headache. I'm joined today by Dr. Jessica Ailani.
She's the first author of a recent publication entitled Safety and Tolerability of Ubrogepant for the acute treatment of migraine and participants taking atogepant for for the preventive treatment of episodic migraine results from the tandem study. Welcome, Dr. Ailani. I'm so happy to talk to you about this important work.
Dr. Jessica Ailani
Thank you so much. And thank you so much for highlighting this study.
Dr. Rashmi Hawker Singh
So first of all, tell me about what you did, why you did the study. Actually, this is something that we talk about quite a bit, I think, in clinical practice. But I want to know what prompted you to actually study this from a trial perspective.
Dr. Jessica Ailani
Yeah. So I just want to really put a shout out to AbbVie, the company that sponsored this trial. This was a thought process when the drugs first came out. It's looking at Etogepant and Ubrogepant and they were going to just do a PK study, which is actually already published, looking at do these two drugs affect the pk? So let's just put it very, very simply for all of our clinicians out there, which I really am just a clinician, this is how I think of myself. So when I think of pk, I'm like, what?
That's like biochem. I don't know what the, what does that really mean? And it's like, oh, does one drug influence how much of the other drug is around? And I look at that and say, how do I know that actually has any value to clinical practice? And is that really going to happen to my patient in practice?
And does that make these two drugs any safer to take together? So I had been talking to the company and really asking and begging and pleading with them, please, you have both these products, can you actually do a phase four trial, open label, have patients take both these drugs together and show us that there's some safety, understanding this won't be a one year long study. That's really the kind of safety we want to know about. But something just show us that when patients take both these drugs together, and I will quote what I said, that they don't blow up from constipation, because that was my largest concern, that people would get so constipated, so backed up they wouldn't poop for months, and this is the kind of thing that I was really concerned about for my clinical practice, for my patients, they're on all these medications that are anticholinergic and slow them down and they have the migraine gut and they're not going to the bathroom. And, I didn't want anyone to end up getting admitted because I decided to put them on these two drugs together based on a PK study.
And it didn't really take too much work to convince them to do this trial. It took a little bit more work to figure out how to order their drugs. So here you had a toga pant for prevention of migraine. You're still not getting over my poop comment, huh? But I really put it that way.
I was convinced no one would poop and that was such a fear. So how do you order it? Do you have them take the acute medication, you bruise your pant first for a while, see that they're doing okay, then add on a preventive or do you start them on the preventive first, make sure they're stable, and then add on the acute treatment in the tandem trial, which is actually not the brightest. So it took me a little while to figure out tandem, like tandem bites. They put the two drugs together, they had them on the preventive atogepant first, had patients on this for about a month, made sure they tolerate it.
And it turns out for most patients they tolerated it pretty well because biggest side effect was constipation, which really mimicked the same rates of constipation in the primary clinical trials. And then they added on Ubrogepant to take as needed when they had migraine attacks. So I don't want to take away any of your shine if you want to ask me questions about.
Dr. Rashmi Hawker Singh
No, I mean, this is the kind of conversation that comes up in clinical practice all the time is this combination okay to take? And what do we know?
And, we like to practice evidence based medicine. So having this data available has really been helpful. So what did you find? What did you and your co ops authors find from this work that you all did?
Dr. Jessica Ailani
The first thing that was really interesting that we didn't think through was once you put a patient on prevention, in our mind this was still early days of anti cgrp.
So we're like, of course you still need an acute treatment because you're going to have migraine attacks. Well, actually a big portion of patients, once they started on a toja pant had a pretty big drop in migraine frequency. They had an average of 5, 7 migraine attacks per month. And very fast. We saw this Drop in frequency.
Not as many needed to use Ubrogepant as we thought we would. We thought we'd have this great collection of seven to eight days a month of patients, on average, taking Ubrogepant during the second part of the trial. So first piece of data was, oh, look at that. Atogepant worked as good in this trial as it did in its original trial. So frequency definitely came down.
Second thing we saw was that ubrojepant on top of atogepant was well tolerated. While patients had constipation that first month, there wasn't increased rates of constipation once they started on Ubrogepant. So unlike my big fear, nobody blew up.
Dr. Rashmi Hawker Singh
And one clarifying question. You had 60 milligrams of atogepant and 100 milligrams of ubrogepant, right?
Dr. Jessica Ailani
Yes, thank you. Very good clarifying question. Yes. We used the max dose to really make sure that patients were exposed to the most. So at 100 milligrams of ubrogepant, it added to the 60 milligrams of etogepam.
There was no increased rates of constipation seen and no other rates of adverse events. There were no changes in LFTs that were seen. There were no increased rates of sedation or any other types of adverse events reported. Again, this is a short trial. It was only about 3 months long total.
But in this time period, we didn't really see any new adverse events occur when patients were adding in Ubrogepant as needed. As I mentioned, it's really important to go back to this concept that frequency dropped. We did have patients who had high frequency and chronic migraine in the study. We did study some patients who were using frequent Ubrogepant in The trial, like 10, 12 days or more a month. It was a very small portion of patients.
The average patient in the study was using it 2, 5 days per month. When I take this in clinical practice, there are a couple of key points here. Yes, it is safe to use a combination. This is the one combination we've studied. Atto 60 Ubro 100 and patients could take a repeat dose if needed.
That was a huge point takeaway. Two, no added increased safety risks or concerns. We don't need to check labs, we don't need to tell our patients there's an increased risk of constipation. Three, we actually don't know for the bulk of people, if they take 10 to 16 times a month of Ubrogepant while on a togepant, what would really happen in the long term? So what I advise my patients is, if you have episodic migraine and you start at TO and you take Ubrogepant as needed, the chance you're going to use a lot of ubrogepant is low.
But if you have chronic migraine and we start you on etogepant, I'm going to watch your frequency of ubrogepant use. And if it's really in the higher numbers, 10, 12 days a month, we may want to consider just watching you long term. Are you starting to develop constipation? Do we need to check your labs? Most of my patients are getting annual labs with their primary.
Do we just want to watch your LFTs over time? Again, we have absolutely nothing to indicate that there's going to be a problem. But this patient type wasn't really the one that was mainly focused on in this study.
Dr. Rashmi Hawker Singh
I think that's really important to know, to mention just because, you know, we had no data up until now and we have some data, but we still have lots of questions that are still left to be answered.
Dr. Jessica Ailani
Yeah.
Dr. Rashmi Hawker Singh
Well, thank you so much for taking the time to speak with me about this work. It's really important to ask her clinical care patients.
Dr. Jessica Ailani
Thank you so much for having me and I hope all of our watchers have learned a little bit of something about this.