Jelena Pavlovic, MD, PhD, on Ubrogepant in the Acute Treatment of Perimenstrual Migraine

In this podcast, Jelena Pavlovic, MD, PhD, discusses the implications of her team's research presented in the session "Ubrogepant Was Safe and Well Tolerated in the Acute Treatment of Perimenstrual Migraine" at the American Academy of Neurology's 2021 Virtual Annual Meeting. 

Additional Resource:


Jelena M. Pavlovic, MD, PhD, is an associate professor of neurology at the Albert Einstein College of Medicine and an attending neurologist at Montefiore headache center in the Bronx, New York.



TRANSCRIPTION:

Jessica Bard: Hello, everyone. Welcome to another installment of "Podcasts360," your go‑to resource for medical news and clinical updates. I'm your moderator, Jessica Bard, with Consultant360 Specialty Network.

Migraine attacks are common among women during monthly menstruation with more than 50 percent of women reporting this symptom. Dr Jelena Pavlovic is here to speak with us about that today. Dr Pavlovic is an associate professor of neurology at the Albert Einstein College of Medicine and an attending neurologist at Montefiore Headache Center in the Bronx, New York.

Thank you for joining us today, Dr Pavlovic. You're presenting your research, Ubrogepant, was safe and well‑tolerated in the acute treatment of perimenstrual migraine at AAN 2021. Can you please give us an overview of your research and its findings?

Dr Jelena Pavlovic: Sure. Thank you for inviting me and for your interest in this topic.

The goal of the study of my colleagues and myself was to determine the efficacy and safety of Ubrogepant, which is a new oral calcitonin gene‑related peptide receptor antagonist, which has been approved for the treatment of acute migraine attacks with and without aura, and used for treatment of perimenstrual migraine attacks.

We know that perimenstrual migraine attacks are the particularly burdensome attacks in women with migraine. The safety and efficacy of Ubrogepant in the treatment of particularly specific perimenstrual attacks had not been previously studied or for that matter of any other gepants.

We conducted a post hoc analysis in which we included menstruating women who treated at least one migraine attack with Ubrogepant. The study consisted of participants of the prior leading trials of ACHIEVE I and II.

This was phase III multicenter, 52‑week open labor, long‑term safety extension, where the participants of ACHIEVE I and II were re‑randomized one to one to one, to usual care Ubrogepant 50 milligrams or Ubrogepant 100 milligrams, the two formulations that are available on the market.

The participants could treat up to eight migraine attacks of any pain severity with Ubrogepant every four weeks at home. Headache diaries were kept.

Perimenstrual migraine attacks were defined, according to the International Classification of Headache Disorders, as attacks that occurred between two days prior to the onset to bleeding and three days after the start of the menstrual bleeding, which was defined as endometrial shedding.

Non‑perimenstrual migraine attacks were defined as attacks outside of minus two to plus three five‑day window. Outcomes of interests were pain freedom and pain relief at two hours, absence of the most bothersome symptom, photophobia, phonophobia, nausea two hours and return to normal function in two hours.

Overall, there were 278 women who were identified to have at least one perimenstrual migraine attack that they treated with Ubrogepant, an attack occurring within those five days of interest in relation to the menstrual bleeding.

Among those women, there were overall within the 52 weeks of observation. 1,329 perimenstrual migraine attacks that were collected, and 16,145 non‑perimenstrual attacks were treated.

Clearly, a very high number of attacks that we had to deal with. There were 137 women in the Ubrogepant 50‑milligram treatment group, and 141 women, so comparable number in the Ubrogepant 100‑milligram treatment group.

Their baseline characteristics in migraine history of the two subgroups were quite comparable. Overall, in terms of results, we saw similar effects of pain freedom and pain relief at two hour were achieved in a similar percentage of perimenstrual migraine attacks and non‑perimenstrual migraine attacks for both of these Ubrogepant treatment groups.

Similar, as well, for absence of photophobia, phonophobia, and nausea were achieved in a similar percentage of whether the attacks are perimenstrual or non‑perimenstrual for both treatment groups. There was no difference between the two percentages in the two subgroups, and two dosages of treatment and return to function in two hours.

Overall adverse events profile for the two subgroups was similar to that observed in the overall population. No significant signal was identified. Overall, we saw across all outcome measures that Ubrogepant was equally efficacious for the treatment of both perimenstrual and non‑perimenstrual attacks.

That is truly important finding, because we know that these perimenstrual attacks are challenging to treat. The fact that it was equally efficacious is very promising. It also supports a notion of having a regimen for women with migraine who experience both types of attacks.

Jessica: You mentioned briefly there why it's so important to study this, but why was it important to study Ubrogepant in this population and for this indication?

Dr Pavlovic: First of all, migraine is a disorder of women of reproductive age. Migraine prevalence peaks in women aged 30 to 39. This is the time when women are supposed to be at their maximum productivity.

Life demands most of them when they're going through pregnancies, lactation, having raising children, having multiple jobs. Losing time due to migraine attacks is a significant loss of productivity and significant loss of work and social functioning.

This is why these perimenstrual attacks that occur in relation to menstruation, and as I mentioned earlier, are defined by International Classification of Headache Disorders, as the five‑day winter world that starts two days prior to the onset of menstruation and the first three days menstruation.

These are the attacks that are the most burdensome for women who have migraine. This is where migraine is at its worse. Experiencing migraine attacks is challenging enough. Then experiencing the perimenstrual attacks is an extra challenge, simply put.

These attacks tend to be, and this has been shown in a number of studies throughout the last two decades, these perimenstrual attacks in women who experienced them tend to be more severe than non‑perimenstrual attacks.

They tend to be associated with more symptoms of migraine, such as photo/phonophobia. They tend to be more burdensome. They tend to last longer. They tend to be refractory to treatment.

Typically, the usual treatment that women take will not work as well. It can often lead to status migrainosus. That is prolonged days of headache. Therefore, a particular need for more effective treatment of these attacks which tend to be where migraine is at it's worse.

What is of note is why we wanted to look into Ubrogepant in this study is because Ubrogepant is, as you know, a relatively new treatment in migraine, a promising new mechanism targeting the CGRP pathway.

Also, what is relevant is that there are currently no FDA‑approved treatments specifically for menstrual‑related migraine or for the perimenstrual attacks. This is an area where there is further need for understanding treatment and for improved treatment specifically in this area of women's health.

Jessica: Overall, you and your colleagues found that nearly significantly more participants taking Ubrogepant 50 milligram had achieved pain freedom at two hours compared with participants undergoing usual care. How will this result impact clinical practice and how perimenstrual migraine is managed?

Dr Pavlovic:  Our results were quite encouraging, given what I have just mentioned, how burdensome perimenstrual attacks tend to be, and how they're typically refractory to treatment, and often require additional treatment and doubling up of the acute treatment of traditional acute treatments.

For example, women who treat with naproxen, they're typical migraine or attacks or with triptans may during the perimenstrual interval need to double up and to use both triptans and N‑sets in combination.

The fact that we were able to observe very comparable similar percentages for both periods of response at two hours of pain freedom and pain relief for both perimenstrual and non‑perimenstrual, Ubrogepant‑treated attacks is very encouraging.

As you point, we've seen almost significant, approaching significance effect for Ubrogepant 50 milligrams for the perimenstrual attacks. There was also a trend with donut reaching significance.

The trend in general was Ubrogepant, the perimenstrual attacks were by percentages purely more responsive to Ubrogepant. High percent of them responded to Ubrogepant 50 and 100 compared to the non‑perimenstrual attacks.

That is quite encouraging and also provoking. We know CGRP and estrogen, which is known to be the triggering factor in perimenstrual attacks, have a complex interaction. Exploring the CGRP pathways and mechanisms in this context of perimenstrual attacks is of great interest. This is just scratching the surface of what hopefully we will be able to study further.

Jessica: You mentioned scratching the surface. What's the next step in your research on this topic?

Dr Pavlovic: One of the obvious takeaway points from this is that having one treatment that is effective for both perimenstrual and non‑perimenstrual attacks is very advantageous and very appealing, prescribing a single drug that works for all attacks, obviously for both the patient and the provider.

What we would like to see further is exploring this window. We went with the very strict criteria for the definition of the perimenstrual migraine attacks, that is the five‑day interval.

We know from other population studies and also from clinical practice that women experience perimenstrual attacks with longer time intervals. Some women reliably start getting attacks, even five days prior to their bleeding, sometimes seven days prior to bleeding. It can last longer.

Exploring a broader window and seeing how those attacks compared to non‑perimenstrual tests, we may see even more of an effect. Here, those attacks were captured as non‑perimenstrual given the very strict ICHD criteria for the definition of perimenstrual migraine attacks. This may further inform the mechanisms that played the role in perimenstrual migraine.

Jessica: Is there anything else that you'd like to add today?

Dr Pavlovic: I'd like to emphasize the need for effective and tolerable treatment of perimenstrual attacks, which are the most burdensome. Very frequently occurring attacks did hold most of the challenges for women with migraine of reproductive age, which is when migraine is more common.

There are currently no FDA‑approved treatments specifically for perimenstrual attacks. The knowledge of the presentation of these attacks and their treatment is highly relevant for quality of life of women with migraine.

Jessica: Thank you so much for your time today. I enjoyed speaking with you.

Dr. Pavlovic: Thank you. Thank you for your interest and your attention.

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