Some 'Novel' Surprises in Epilepsy Data

Andrew N. Wilner, MD; Joseph Sirven, MD


June 11, 2021

This transcript has been edited for clarity.

Andrew N. Wilner, MD: Welcome to Medscape. I'm Dr Andrew Wilner. My guest is Dr Joseph Sirven. Welcome, Joe.

Joseph Sirven, MD: It's a pleasure to be here talking with you today.

Wilner: I'd like to begin by hearing your thoughts on what was new and interesting in the world of epilepsy at this year's annual meeting of American Academy of Neurology (AAN).

Sirven: I'm amazed that with all we've been through this year — COVID-19, a sense of racial injustice leading to concerns about social determinants of health, a reinvigoration of the interest in population health — that AAN 2021 still provided novel ways to be surprised. This virtual meeting definitely kept up with the high level of expectations raised by previous years.

I think the first thing that struck me was the number of projects — including one I was involved with — looking at issues going on upstream to the management of patients with epilepsy, rather than focusing on what's happening in the exam room. That kind of took me by surprise, and happily so, because it's good to see research in that area.

The second thing that stood out to me was seeing some results that have recently emerged from previous ongoing studies. I'm specifically talking about things like the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, where they looked at what happens to children of mothers who are exposed to newer antiseizure medications.

These were the biggest take-home messages for me from the 2021 meeting: the focus on population health–based studies and the unique spectrum of pregnant women treated with antiseizure medications.

MONEAD's Findings on Antiseizure Medication Use During Pregnancy

Wilner: Let's talk about the second one for a moment. Of course, teratogenicity is a big concern and we know it can occur with the older antiseizure medicines. It was initially felt that the newer medications were safer in this respect, but that interpretation was based on limited data; it all looked good simply because we hadn't yet seen anything bad. Now that we have a lot more experience and data, is it still true that the newer medications are safer for women who are or plan to become pregnant?

Sirven: I believe it's starting to look like they do seem safer than what we knew in the past. It's all about what you judge it against. In the last iteration of these studies, the comparison was always with valproic acid, Depakote, and these first-generation agents that caused a lot of problems and concerns.

Results from these preliminary analyses show that this isn't so much of a problem with lamotrigine or levetiracetam. The verdict isn't completely in yet, because we still require substantially more data in lots of women. However, it is somewhat reassuring that they're not picking up these obvious or overt negative aspects.

That doesn't mean that can't happen on an individual level, so you can't let down your guard. When treating these patients, you still have to get a perinatologist involved, have them on folic acid, and things of that sort.

But the reality is it's not showing up to the same level of before where we might think, "Oh my goodness, we need to avoid this drug. This is a disaster." That didn't come out from these results.

Wilner: That's great to hear, because women with epilepsy need to keep it controlled one way or another while they're pregnant. We've learned that valproic acid is off the list because it causes developmental delay and neural tube defects, but we now have so many other choices that that really shouldn't be an issue. Is it still true, though, that dosing matters in these patients?

Sirven: To some degree there is an element of dosing. These medications were assessed at the levels they're used to prevent seizures, but they're also used for other purposes, such as for mood or pain management, where the dosing can be less. So, I'll say that the verdict isn't completely altogether in, but the results seem more optimistic than they were in previous iterations of this study.

Wilner: Allow me to put you on the spot. All other things being equal, if you have to choose a medication for a woman with epilepsy, do you have a number-one option in terms of safety?

Sirven: I still believe that the data favor levetiracetam. That's assuming that there's no contraindication from a psychological/psychiatric standpoint. But for me, levetiracetam is the preferred medication in these patients, and the MONEAD study did nothing to dissuade me from that decision.

Wilner: On a clinical note, I want to highlight for those choosing to use levetiracetam that there can be pretty wide fluctuations of drug levels during pregnancy. It's therefore important to monitor those levels continually during pregnancy, at least every trimester — although some will do so every month — to ensure that they stay within the therapeutic range. Would you agree with that?

Sirven: One hundred percent. Levetiracetam is very water soluble, so there's going to be a lot of volume changes, and its half-life can be somewhat shorter, particularly with the immediate-release versions. So you do have to check those levels, ensure that patients are being adherent to the medication, and be knowledgeable about the potential for a change in volume that occurs over pregnancy and having to adjust for that.

Factors Contributing to the Epilepsy Treatment Gap

Wilner: Earlier you mentioned research touching on social and epidemiologic issues. Can you comment further on that?

Sirven: There was a lot of wonderful research that occurred in regard to the social determinants of health. In one study that I was personally involved with, we examined Arizona Medicaid claims, which involved anyone who had epilepsy living in that state. By using claims data, we were able to obtain a clear definition of epilepsy to the degree that we can examine what happens in terms of management, including when they receive their diagnosis, how quickly they're managed, if they're even managed with a seizure medication as the first step of treatment. When you're a part of this Medicaid program, you have to fill out extensive evaluation information, such as whether they cover your prescription, whether it gets filled, where you live, your employment status, your salary. It's a treasure trove of demographic data. And it comes from what is considered to be one of the model insurance groups in the United States.

We looked at data from approximately 6500 patients in the state of Arizona from 2015 to 2019. We found that a significant percentage of the population, somewhere around the 45%-48% range, never received treatment at all, regardless of the diagnosis. Even among those who did get treated, the average delay until that began was somewhere between 3 and 6 months, with 6 months being the more common number.

We saw that certain demographic factors impacted whether you were delayed in treatment or received no treatment at all. Those included ethnic group eg, Native Americans), being unemployed, being homeless, and having been widowed or divorced (ie, living alone). Those all seemed to play into the mix.

Wilner: Although those results don't come as a surprise, it's nice to have it quantified. For example, I'm always aware of how many epilepsy patients who require frequent visits can't drive. So right away, they're behind the eight ball. Even though they have to come to the doctor, it's very difficult for them to do so.

It may be that telemedicine visits will help in this epilepsy population that's stuck at home, and that would certainly make for an interesting topic of study.

And, of course, many people with epilepsy have memory problems, which makes it difficult for them to take their medication regularly and is going to negatively impact adherence.

Sirven: That was what was sad about seeing these results. Even though we just look at patients living in Arizona, this is considered one of the model insurance groups in the country, which means this may be as good as it gets in these patients.

Whether that's what it looks like in commercial insurance and other groups, we don't know. But it does seem to be somewhat consistent with what's been published to date on the national scale. That kind of helps confirm that we have a problem.

Wilner: Joe, this has been a really great discussion. I want to thank you for sharing your insights and observations regarding advances in epilepsy presented at the 2021 AAN meeting.

Sirven: You're so welcome. It's a pleasure to talk to you and something I always look forward to.

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