Lower Mortality Rates in Epilepsy Treated with Cenobamate
Abstract number :
2.343
Submission category :
7. Anti-seizure Medications / 7C. Cohort Studies
Year :
2025
Submission ID :
167
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Katie McFarlane, MS – University of Pittsburgh Neurology
Kyr Goyette, Student – University of Pittsburgh
Stephen Koscumb, BS – University of Pittsburgh Medical Center
Wesley Kerr, MD, PhD – University of Pittsburgh Neurology
Rationale: Medication-resistant epilepsy (MRE) is the failure of 2 appropriately chosen and tolerated antiseizure medications (ASMs) to produce seizure freedom. Compared to other ASMs, cenobamate may produce higher rates of seizure freedom. One effect of improved seizure freedom may be reduced excess mortality associated with epilepsy (ES) including Sudden Unexpected Death in Epilepsy (SUDEP), other seizure-related causes, and other contributors. While historically excess mortality in MRE was twice as high as in standardized reference populations, the mortality rate in clinical trials of cenobamate was not significantly different than population averages. To investigate if that benefit was observed in real-world data, we compared mortality rates in patients with ES treated with cenobamate to those treated with other ASMs.
Methods: We examined electronic health records for patients of all ages with a prescription for cenobamate or another ASM prescribed at the University of Pittsburgh Medical Center (UPMC) from 2020 to 2025, with mortality information supplemented by state and federal mortality registries. ES was identified using the International Classification of Disease Codes Version 10 (ICD-10) G40 plus ASMs. MRE was identified as ES plus an intractable ICD-10 code or at least 3 ASMs. Prescription records identified new starts of cenobamate or other ASMs. Time from first prescription until last follow up or death was evaluated using standardized mortality ratio (SMR) and Cox Proportional Hazards to separate the effect of ASMs from that of age, sex, race, ethnicity, ES-specific characteristics, and co-occurring conditions. We also categorized deaths based on certainty of SUDEP.
Results: We identified 24,603 patients with non-MRE (median ASMs 1) and 5,469 patients with MRE (median ASMs 3) with new prescriptions, including 401 patients prescribed cenobamate (age range 8.5-83.6, median age 37, 49% female). Patients had a median 3.2 years of follow-up (interquartile range 1.5-4.2), with 86,443 total patient-years of observation. After accounting for differences in age, sex, race, and ethnicity, the SMR of non-MRE was 2.46 (1,849 deaths, 95% Confidence Interval [CI] 2.35-2.57) and MRE was 3.56 (379 deaths, 95% CI 3.21-3.94). While all patients prescribed cenobamate had MRE, the SMR was 2.23 (7 deaths, 95% CI 0.89-4.75). Of the deaths, 1 (14%, 95% CI 0-43%) was probable SUDEP, 1 was seizure-related non-SUDEP, 4 were not seizure or SUDEP related, and 1 had unknown circumstances. After accounting for other characteristics, cenobamate was associated with a 92% lower mortality rate than comparable patients prescribed other ASMs (Hazard Ratio 0.08, 95% CI 0.03-0.19, p< 0.0001).
Anti-seizure Medications