The study author, director of MedStar Georgetown Headache Center, and associate professor of neurology at MedStar Georgetown University Hospital discussed the findings of a pooled analysis of the ACHIEVE I and II studies of ubrogepant.
Jessica Ailani, MD
At the now-canceled American Academy of Neurology (AAN) 2020 Annual Meeting
, a number of analyses of pooled data on ubrogepant (Ubrelvy; Allergan) were scheduled to be presented. One of those presentations on the recently approved agent for the acute treatment of migraine with or without aura in adults centered around its effectiveness and safety in patients who took an optional second dose.
The findings on that optional second dose of the anti-calcitonin gene-related peptide (CGRP) medicine revealed that ubrogepant is the first and only treatment to demonstrate statistically higher rates of pain freedom at a second dose compared to placebo, without additional safety concerns identified. The analysis was conducted by Jessica Ailani, MD, FAHS, director, MedStar Georgetown Headache Center, and associate professor of neurology, MedStar Georgetown University Hospital, and colleagues.
To find out more about these data and what they mean for the clinical care of acute migraine, NeurologyLive
reached out to Ailani. She shared her and her colleagues’ reasoning for conducting the analysis, and her perspective on what these data mean for migraine specialists.
NeurologyLive: What prompted this analysis with ubrogepant?
Jessica Ailani, MD:
When we look at patients who have migraine attacks and are using acute treatment, we know clinically that often patients will take a second dose of medication, especially if they felt that they're starting to feel better but they don't quite have the effect that they're hoping for—they tend to re-dose. We really wanted to know if you took a second dose of the drug, was it effective, was it safe, was it well-tolerated, and if it was effective what were the time points we’re looking at? Was there 2-hour pain freedom, or are we just feeling a little bit better?
We were hoping that this would really help lead to an answer to these questions so we can make clinical recommendations when we're seeing patients in practice. That yes, if you take a second dose, you're going to feel better or, don't bother taking a second dose because it doesn't really do very much. The important thing that we have here now is proving that a second dose is effective, and proving that not only is it effective, but if you take it and you already had some pain relief, you have a better chance of reaching pain freedom. I think, clinically, that's really important to patients.
The second part of that is that patients tolerated the second dose really well, with the side-effect and adverse event profiles being similar to taking just a single dose. I think for patients, that's probably 1 of the more important features—”If I go ahead and take another dose, I'm going to be fine. I'm going to feel fine. I'm going to feel the same,” and, in fact, clinically this is what we've been hearing with patients who are using ubrogepant. They don't even realize they took anything, they're having minimal side effects, and for our patients that took the second dose, they're saying the same thing. They don't feel drugged or over-sedated, or even that they've taken any medicine—they just start to notice they're feeling better. I think that's really important for us to have that safety information and then back that up by what we're seeing clinically.
Were the findings surprising or unexpected in any way?
I do think it was surprising we saw an effect. We're very used to thinking that if a single dose of a medication doesn't work, you have to move to a different class. That's what we see with the triptans, and when we look at the other medications that are new in this category—lasmiditan as a ditan and rimegepant as a gepant—neither of them had second dose options, neither of them showed the second dose as effective. So, this was actually very surprising for ubrogepant.
Another surprising and really amazing bit of information is that side effect profile. Again, we think as you get higher on a dose, you're going to experience more side effects and so that might limit the all-at-once, higher amount dosing, but we didn't see that here. So again, 2 really important pieces of information that I don't think we were expecting to see.
Do these results suggest that perhaps there might be a population of patients who would benefit from a single higher dose of ubrogepant?
This abstract in particular did a pooled analysis of both ACHIEVE I and ACHIEVE II, so it looked at various doses. We have the most patients for the 50-mg dose, based on the fact that 50 mg was studied in ACHIEVE I and ACHIEVE II, and so, in this particular abstract the 50-mg dose is what showed statistical significance for the second dose. But I think what you're asking is a fantastic question and is often what we're thinking about in clinic. If I give my patient a starting dose of 50 mg and repeat the dose in 2 hours and they feel better, what do I do clinically? Often, these are the patients to who, I will say, “Hey, you know what, why don't we bump you up to 100 mg and see if that makes a difference?” and then, “How often do you need to take a second 100 mg dose?” I do think that would be wonderful if we had more data to study that. Unfortunately, since 100 mg was only studied in ACHIEVE I, there's not enough pooled data to really say if a second dose of 100 mg is statistically significant.
I think we're going to end up with—without even doing a clinical trial—is a lot more information in the next year about this. If you switch them to the 100-mg tablet, are they repeating as often, do they need to repeat as often, or is this a good indicator that the split dosing works better than just taking the lumped dose of a 100-mg all at once?
What are the main takeaways for the clinical community?
The takeaway, I would say, from this data is that a second dose of ubrogepant is effective for patients, especially looking at the 50-mg dose; that there's a higher chance of achieving pain freedom with the second dose than a single dose alone, especially if your patient was already having pain relief; and that the second dose is well tolerated. So consider this in your patients that tend to want to repeat dosing.
This is something that I bring up with my patients when we're trying to make a choice on acute medication—how do I choose between these 3 great new options for patients? Well, I tell them 2 of them are single-dose options and 1 is a repeat-dose option, and it is amazing to see how often patients have a preference. Do they want a 1-dose and they're finished or do they want the option of a second dose? I would say it's a lot more popular for patients to want to be able to take a second dose if they need to. If they think the effect isn't enough or not fast enough or they feel like, “Yeah, well sometimes I feel better, but it still comes back in the same day based on my experience in the past, I really like that safety option for myself.” I think that's really important in how we present this to our patients. I think that's a great takeaway message.
Transcript edited for clarity. For more AAN coverage, click here.
Ailani J, Blumenfeld A, Klein B, et al. An Optional Second Dose of Ubrogepant is Effective in Achieving 2-Hour Pain Freedom in the Acute Treatment of Migraine. Neurology. 2020;94(15 Suppl): 166.