NeuroVoices: Jessica Ailani, MD, on Implications of DELIVER Analysis With Eptinezumab for Migraine Prevention

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The director of the MedStar Georgetown Headache Center talked about results from an analysis on the DELIVER study assessing response rates of eptinezumab in patients with migraine over an 18-month period.

Jessica Ailani, MD  (Credit: MedStar Georgetown Headache Center)

Jessica Ailani, MD

(Credit: MedStar Health)

Migraine is considered one of the most disabling neurological conditions worldwide, and patients may often experience a substantial amount of impairment to their daily activities and quality of life.1 Furthermore, there are a group of patients who have difficult-to-treat migraine that may often cycle through different preventive therapies. In a recent cross-sectional analysis published in The Journal of Headache and Pain, findings showed an increased burden, quality-of-life impairment, and functional impairment in patients with migraine who had at least 4 monthly headache days and more treatment failures, suggesting the need for effective preventive migraine treatments.2

DELIVER is a multi-site, randomized, parallel-group, double-blinded, placebo-controlled trial (NCT04418765) assessing eptinezumab (Vyepti; Lundbeck) as a preventive treatment for patients who have previously failed a few preventive migraine therapies. Previous results from DELIVER revealed that patients on eptinezumab had significant reductions in mean monthly migraine days, with greater achievement of at least a 50% migraine response compared with placebo over 18 months. A recent analysis of the trial showed that a clinical response to eptinezumab was maintained in most patients if they reported an at least a 50% migraine response following 1–2 doses of the treatment.3

Lead author Jessica Ailani, MD, director of the MedStar Georgetown Headache Center, presented these recent findings at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado. For those who had at least 50% migraine response after the first dose, 61% and 74% maintained an at least 50% response to eptinezumab 100 mg (n = 113) and eptinezumab 300 mg (n = 126), respectively, for 18 months. For those who achieved at least a 50% migraine response to the first 2 doses of eptinezumab, 69% of those on eptinezumab 100 mg (n = 128) and 82% of those on 300 mg (n = 131) maintained a 50% responder status over the remaining 4 doses.

In a new iteration of NeuroVoices, Ailani, who also serves as a clinical professor of neurology at MedStar's Georgetown University Hospital, recently sat down with NeurologyLive® in an interview to discuss how the efficacy of eptinezumab in the DELIVER trial analysis compared with other migraine treatments. She also spoke about the implications of these latest findings for long-term migraine management. In addition, Ailani talked about how clinicians use these results to support patients who have experienced previous treatment failures.

Top Clinical Takeaways

  • Patients with migraines who initially respond well to eptinezumab are likely to sustain a high response rate over 18 months.
  • Even if patients experience occasional setbacks, continuing eptinezumab treatment generally results in consistent long-term efficacy.
  • These findings offer hope and guidance for clinicians in managing patients with migraines, especially those with a history of treatment failures.

NeurologyLive: Could you provide an overview of the findings from the analysis?

Jessica Ailani, MD: The DELIVER study is a large multicenter, multinational, placebo controlled randomized trial that looked at patients who were placed on eptinezumab 100 mg or 300 mg versus placebo. These are patients who have tried 2 to 4 other traditional medications in the past and have not found them to be effective. These are traditional oral medications, patients who were on a botulinum toxin, not other CGRP monoclonal antibodies or gepants, they weren't available at the time of the study. These patients were initiated into the trial and given treatments over 18 months, the treatments are every 3 months. This is an intravenous treatment for prevention of episodic or chronic migraine in adults. The patients in this trial either had episodic or chronic migraine.

We wanted to analyze the data and say, ‘what if after the first infusion you had a greater than 50% response rate? How do you do through the rest of the time period in the trial?’ It’s a very clinically relevant question because if a patient comes in after their first infusion, and is doing really well, they're going to want to know, ‘well, is this it? Am I going to get better? Am I going to keep doing well? Or am I going to crash?’ There's always this fear, especially in a patient who's tried other treatments that say, ‘hey, this is a one time thing. It's a fluke. I did well, I'm not going to do well again, can I have faith that this is going to work?’ Then what about the patient who does well for 2 cycles? How does their progress look over the course of 18 months of treatment?

We did an analysis of both these types of groups, those that did well in the first treatment and then those that did well after 2 treatments. How did they do over the course of these 18 months when they had several treatments given? Just the skinny of the data, because it's a lot of information: If you did well greater than 50% response in that first treatment dose, the chances of you doing well for the full 18 months were very high. We're looking at above 60% of those given 100 milligrams. About 62% to 69% had a greater than 50% response for all doses given. Somewhere close to almost 70% at the 300 mg had a greater than 50% response for all the doses. If you did greater than 50% in the first 2 doses, your chance of doing well for the rest of the 18 months continued to be really high with those at 300 mg reaching almost a high 70% and similar in the high 60% for those at 100 milligrams.

Regardless of the dose, if you responded well in that first infusion, you responded well for the entire time. Now what's the flip of this? What if you responded well the first month of your first infusion in the trial? We know that migraine is a very complex disorder. In clinical practice, we can see that a patient is doing well on their treatment and hits that migraine bump which Richard B. Lipton, MD, has well described as the migraine roller coaster. This is where the disease process itself will have its ups and downs. I always love to bring that analogy back to my clinic because in clinical practice, we see this all the time. A patient is doing really well and then all of a sudden, they have a couple of bad months. There's that fear of I’m doing so great am I going to go back to where I was before, completely disabled, unable to do things? Do I need to change to preventive treatment?

Another insight we got from this trial is a patient can do really well that first or the 2 infusions, and generally will continue to do well even if they don't do well the whole consistent time. They can have a couple of infusions, they do well and might hit a couple of bumps in the road. I think that's another really important takeaway, though the top line data was extremely wonderful. Every time I look at the data, I get excited like wow these patients can do consistently well for a long time.

If you look down the data line that patients might not have an extremely great response every round, they generally will have a very good response for most of the rounds with patients having up to about 90% chance of greater than 50% response for the bulk of the treatment rounds. As a clinician, that tells me if a patient has a bad 3 months to keep going with treatment. Now if they have a bad 6 months, that's when I might reevaluate and say ‘hey, maybe it's time for us to think about other options and either add or take away or change.’ Again, extremely relevant to clinical practice and a very important take home message.

What was your reaction to the results in the analysis and did you find anything surprising?

It was an amazing data analysis that we were able to analyze. I think we expected it to have some good findings, but I don't think we expected it to be this amazing. Also, the relevance to clinical practice what we're going to be able to tell our patients with confidence after having this data analysis. That is extremely important to a patient who for the first time is having success in their treatment, especially in migraine, which is such a disabling disease for someone who might not have any other medical problems. Especially in someone who in the DELIVER population has tried other treatments and has felt the sense of failure.

Oftentimes these patients come to us feeling like, ‘are you sure this is migraine because everything is failing me? Are you sure there's not something else wrong with me?’ For the first time they might take a very specific treatment for migraine and have this, ‘Oh my gosh like is this the way I was supposed to feel the whole time,’ and really come out of it feeling amazing. If they have that bump, that fear comes back. To have results like this that really say the data shows us that there's a very like somewhere of a 90% chance that if we continue, you're going to go back to having that greater than 50% response if that's who you were after the first 2 rounds.

What advice do you have for clinicians who see patients with migraine and feel distraught from previous failure of treatments?

I do think it's very difficult for patients with migraine to go through the system. There's a lot of great data that's been presented at the AAN this year that goes through the patient journey, and how many times they might have gone through the healthcare system and felt that sense of disappointment. As a clinician, it's very hard for us because the anger sometimes comes out on us. I's very difficult for us to continue being positive and try to take that anger on and say like, ‘it's going to be okay.’ I think understanding where the person is coming from is first and foremost, even in our busy day when we're like 30 patients in and you're like ‘I don't have a time for this.’

Take that moment, take that deep breath and realize a lot of the anger comes from their frustration with the disease process and reflect that back to them. I hear you're upset. I know, this is a difficult journey because this disease is so terrible. I know you've taken a lot of treatments; I can see that I can see where you're coming from. There's still some new treatments out there and if those are failing you as well, there are new treatments that are in clinical trials right now.

I think it's important to reflect that back to them that even if they haven't found the right treatment at this moment, they're still treatments in trials that are different from what are currently out there. That there are still treatments out there for them. Hope is still existent. We haven't found all the right targets. It's not like CGRP is going to be the end game for everybody. We know that and just hang in there.

What do you think is important for clinicians to know going forward to empower their patients with migraine?

I think what's important for people to hear is there is still more and people aren't giving up.As the clinician, sometimes just having that person that is saying, there's more maybe I'm not the right person, but let's find you someone else that can help you, let me be that link for you. Let me try to find a trial for you. Let me be the one that hears your anger and try to help you understand that I understand that your anger is really about your disease, which is a terrible disease. It is definitely hard on us, 100%. I'm always there getting yelled at and get that sense of wow this is really tough. But I always remind myself the anger, the distrust, the everything going on is because of everything out there and what they're going through.

When you take that moment to deflect some of that and ease the situation, what comes out on the other end is trust. The realization that while they're so frustrated because I would also hate that if there was no treatment that was working for me and I was in a situation where I was scared, and I didn't feel like anyone could help me. If you just take that moment to have that, well, maybe there's something I can do and find the right place for them. Take that moment to reflect that it really does change the dynamic and even just doing that finding a person for them to see is a huge step in the right direction.

When we see the patient as a next step, I'll tell you how often they're grateful for their general neurologist, their primary care physician. We hear that positive, I always wish that they call them like, ‘did you tell your doctor that you love them?’ That's really important as well. I think just trying to keep that hope going and realizing there are trials in development, that trials ongoing for treatments that are not yet out there that are focused on different targets for those that have not yet found the treatment that's working for them.

Transcript edited for clarity.Click here to view more NeuroVoices.

REFERENCES
1. Pozo-Rosich P, Lucas C, Watson DPB, et al. Burden of Migraine in Patients With Preventive Treatment Failure Attending European Headache Specialist Centers: Real-World Evidence From the BECOME Study. Pain Ther. 2021;10(2):1691-1708. doi:10.1007/s40122-021-00331-3
2. Buse DC, Pozo-Rosich P, Dupont-Benjamin L, et al. Impact of headache frequency and preventive medication failure on quality of life, functioning, and costs among individuals with migraine across several European countries: need for effective preventive treatment. J Headache Pain. 2023;24(1):115. Published 2023 Aug 24. doi:10.1186/s10194-023-01655-5
3. Ailani J, Soni-Brahmbhatt S, Awad S, et al. Long-term Maintenance of ≥50% Migraine Response with Eptinezumab Treatment in Patients with 2–4 Prior Preventive Migraine Treatment Failures. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
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