Authors :
Presenting Author: Ojas Potnis, BS, MS – Enmed - Texas A&M School of Medicine
Aaron Smith, BSN, RN – NYU Langone; Barry Gidal, PharmD, RPh – University of Wisconsin-Madison; Bassel Abou-Khalil, MD – Vanderbilt University Medical Center; Pavel Klein, MD – Mid-Atlantic Epilepsy and Sleep Center; Jacqueline French, MD – NYU Grossman School of Medicine; Manisha Holmes, MD – Westchester Medical Center
Rationale:
Cenobamate is a new antiseizure medication (ASM) introduced in 2019. The Human Epilepsy Project 2 (HEP2) provides a unique opportunity to analyze cenobamate use and efficacy in a multicenter cohort of subjects with focal treatment resistant epilepsy followed in the real world with 18-36 months of follow up.
Methods:
HEP2 was a prospective, observational study of patients with refractory focal epilepsy. All subjects had at least two focal seizures and at least one observable seizure per month. Participants were 16–65 years old, previously failed at least 4 ASMs (at least two due to failure of seizure control), and were on at least one ASM at enrollment. Subjects were recruited from 10 US epilepsy centers starting 7/31/2018 and were followed for 18–36 months. Aggregate data from monthly coordinator check-ins and medical records were used to assess cenobamate use, dates of initiation, dose changes, discontinuation. Seizure frequency was determined from monthly coordinator check-ins, seizure diary, and medical records. A therapeutic cenobamate regimen was defined as a daily dose of 200 mg or greater for at least two weeks. One subject entered the study already on cenobamate and was excluded from calculations of mean and median therapeutic duration and seizure frequency as an outlier. Three additional subjects didn’t have seizure frequency data recorded during cenobamate use. Seizure frequency was averaged per subject for three months pre-cenobamate initiation and for therapeutic dosing duration. Percent change between these two time points was calculated per subject and then averaged for all subjects. Neuromodulation device and surgery data were also collected. Subject demographic data collected at enrollment.
Results:
Of 154 enrolled subjects, 27 (17.5%) were on cenobamate. 8/27 (30%) were male, 19 (70%) female. Fifteen (55.5%) reached a therapeutic regimen. A total of 7/15 (47%) were male, 8/15 (53%) female. Mean duration on therapeutic cenobamate doses was 29.8±22.4 weeks and median was 38.4 [4.9, 49.3] weeks. A total of 13 remained on therapeutic doses at point of last contact. A total of 14/27 subjects discontinued cenobamate, two of whom discontinued after reaching a therapeutic dose for at least two weeks. One patient started cenobamate before the study and had a therapeutic duration of 311.4 weeks. A total of 10 patients concurrently had neuromodulatory devices (7 VNS, 3 RNS); one had a device (VNS) placed while on a therapeutic dose of cenobamate. One patient underwent resection prior to enrollment, one additional patient after enrollment. Both subsequently started cenobamate. Average seizure frequency percent reduction was 44.3±44.5% and median was 51.3 [36.4,73.8]%. No seizure free periods were seen.
Conclusions:
In this refractory focal epilepsy cohort treated at tertiary referral centers across the US, 17.5% were prescribed cenobamate and 55.5% reached therapeutic doses maintained for a mean and median of 29.8 ± 22.4 weeks and 38.4 [4.9, 49.3] weeks. There was a median percent reduction of 51.3% in seizure frequency while on a therapeutic regimen of cenobamate. Future directions will involve assessing coadministered ASMs, neuromodulation device adjustments, and reasons for discontinuation during cenobamate use.
Funding:
UCB, Neurelis, SK Life Sciences