Prior small retrospective studies reported on the benefit of off-label cenobamate (Xcopri; SK Life Science), an FDA-approved antiseizure medication (ASM), in pediatric patients with drug-resistant epilepsy. A new analysis using data from a national claims database showed that in comparison with previously used ASMs, cenobamate was associated with lower inpatient days and emergency room (ER) visits in pediatric patients with intractable focal epilepsy. In the analysis, investigators assessed pediatric patients with intractable focal seizures who had taken at least 2 prescription fills of cenobamate and had at least 180 days of medical and pharmacy enrollment before and after initiating the drug.1
Researchers compared healthcare utilization outcomes such as epilepsy-related inpatient days and ER visit days during the patient’s previous line of therapy to that of cenobamate. Among 176 patients, the median line duration was 333 days for cenobamate compared with 365 days for the previous ASMs. The most common previous ASM lines of therapy reported were cannabidiol (n = 31), clobazam (n = 23), and lacosamide (n = 16). Notably, treatment with cenobamate improved the rate of epilepsy-related inpatient days from 5.39 days per year to 4.19 per year, and the rate of epilepsy-related ER days from 0.82 days per year to 0.58 per year. All told, 31.8% of these pediatric patients treated with cenobamate required a new ASM to be added.
These findings were presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, by lead author Kate Labiner, MD, and colleagues. Labiner, pediatric epileptologist at Child Neurology Consultants of Austin, had a conversation with NeurologyLive® at the meeting to further talk about the impact of cenobamate on the frequency of seizures in pediatric patients with refractory epilepsy. She also spoke about the challenges that arise when treating pediatric refractory epilepsy in comparison with the adult patient population. Additionally, Labiner discussed how research in pediatric refractory epilepsy could be broadened to benefit a wider range of patients.
Top Clinical Takeaways
- Cenobamate demonstrated effectiveness in reducing inpatient days, ER visits, and the need for additional therapies in pediatric patients with refractory epilepsy.
- Treatment options for patients with pediatric epilepsy are often limited by the form and presentation of medication, as children may struggle with swallowing tablets.
- Research into pediatric refractory epilepsy is growing and focusing not only on seizure control but also on quality of life and the broader impact of treatments on patients.
NeurologyLive: Could you provide an overview of your presentation on cenobamate in the pediatric epilepsy population?
Kate Labiner, MD: We specifically looked at the population age from 0 to under 18 who had refractory focal epilepsy. These are pediatric patients who have failed at least 2 medications and most of them were also on other medications at the same time. So, these patients have failed at least 2, took multiple medicines, and continued to have seizures despite that. We looked at the claims-based data in which cenobamate was once added in comparison with the previous treatment they had been on. We used the input measures of inpatient days in the hospital, number of ER visits, new therapies being initiated, and emergency medicine use days.
What implications do these findings have for patients on cenobamate?
Overall, we were able to show that once patients started cenobamate, they had less inpatient days, less ER visits, and less days spent in the epilepsy monitoring unit. Also, they were less likely to have to add in a new therapy at the same time in comparison with their previously tried meds. In the refractory pediatric population, we defined that as pediatric patients who typically fail at least 1 medicine or 2 medicines and continuing to have seizures. The average for these patients in this population was 5 medicines but the range was up to 13 treatments as we did have patients who failed as many as 13 medications previously.
What are your thoughts on the high number of medications that patient previously fail and what does that say about cenobamate?
It's very common for our patients to have failed many medications and different physicians have been practicing different ways. For me personally, I tend to be a little more aggressive. My patients are often moving through medications quite quickly because if you can get them to max dosing or a dose that's appropriate for their weight and they're still having seizures, then there's no reason to keep them going on that. We will often then switch them out. It's not uncommon for the refractory patients to have failed 5, 6, 7, 8 medicines by the time they're starting to try things that can work.
Once you have tried multiple medications, by the third medicine there's only about a 6% chance that it's going to take you to seizure freedom. So, with the number of medicines you try, the chances that you're going to have success are going to go down. When we can find something like cenobamate that we can add in and they're less likely to have to go to another medicine, be in the ER, and have to be impatient because of their epilepsy, tells us that it's working, whether it be with medicines or potentially in replacement of some of their other medicines. In this data, in the Lennox-Gastaut population and also in the focal population, we saw kids become seizure free which was not previously true for many of them.
Do you have any closing remarks about this analysis with your clinical viewpoint in pediatric epilepsy?
For us, looking at our refractory populations that don't fall into some of those clearly defined populations is big in pediatrics. It's something that is often missing because they are pediatric patients. A lot of the data, which is true across all of medicine, starts with the aged 18 population. Then we either get the trickledown effect in pediatrics where we're able to use it because we know that it works, or we can use it once we prove it safe. But we may not have all the data to say this is the dosing that we should be using, or this is the way we should be using the medicines.
A lot of the research is based on the Dravet (syndrome), LGS, or tuberous sclerosis populations because they are clearly defined conditions that we know are less likely to be refractory. We can say ‘that's an inclusion criterion’ as opposed to the pediatric patients with refractory epilepsy where you may say, ‘you have different epilepsy types’. You can have generalized (seizures), you can have focal (seizures), but they don't fall into neat little categories. Being able to open up research to refractory patients who don’t fall into those categories, then opens up the chances that we can use these medicines outside of the LGS and Dravet populations.
A lot of the pediatric medicines when they come onto the market may be only FDA approved for Dravet or LGS. Yet we have a huge population that's refractory outside of those 2 conditions. For us to be able to open it up to those patients from the early onset of the research could help us get it for them down the road and long term, opening it up for use is those that don't fall into categories nice and neatly.
What other types of research is needed for this pediatric population?
We are all about epilepsy research and pediatric research in general. It's a unique population because we get to help the parents and then also the patients themselves. One of the big things is looking at the quality of life for parents and patients, as a unique population. What matters to our patients may not necessarily matter to their parents and vice versa. Parents worry a lot about the number of seizures that their child is having, and kids may worry about: what do things taste like? How many times in a day do I have to take that? Does it come in a flavor with flavor options? Or does it come in a chewable or just a liquid? Those are things that don't often get addressed in the adult populations.
When we get the medicines, they may only come in a tablet. A huge percentage of my population can't swallow a tablet. By then, they're already taken out from that as a treatment option solely because it doesn't come in a way that we can get it into them. If you can't crush it, that also takes them out of that option. If anyone who's ever tried to open a capsule and shake it out, it's disgusting. None of the kids want to take that and so it is an interesting population for that. Also, making sure that we are limiting the adverse effects because in the adult populations they worry about things like work.
My patients have to go to school, that's not an option for them. That's part of their requirement as kids, to go to school. We look at adverse effects from a different aspect because it can't be something that keeps them so sleepy that they can't function in school or participate in getting physical therapy or occupational therapy. Then when you add on to that, how many medicines are they on? Does it slow their cognitive abilities? For adults, you may be able to get them work excuses like Family and Medical Leave or things like that when you're titrating these meds. I can't pull a kid out of school to do that same thing. It does limit us in that way. Being able to look at all those aspects in pediatrics research is a huge area of growth. It's an area that has grown substantially in the last 5 to 10 years and is continuing to grow looking at quality of life for these kids. This includes asking not just "does it work for their epilepsy, yes or no?" But also if it's working for their epilepsy, how is it affecting the other areas of their lives too.
Transcript edited for clarity. Click here for more coverage of AAN 2024.
REFERENCES
1. Labiner K, Stern S, Wade C, Weingarten M. Effectiveness of Cenobamate in Pediatric Patients with Intractable Focal Seizures: A Retrospective Claims-based Analysis. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.
