Authors :
Presenting Author: Philip Webber, PhD – SK Life Science, Inc.
Emily T. Klatte, MD – OhioHealth
Michael R. Sperling, MD – Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University
William E. Rosenfeld, MD – Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, USA
Marc Kamin, MD – SK Life Science, Inc.
Stern Sean, MS – SK Life Science, Inc.
Clarence T. Wade, MBA – SK Life Science, Inc.
Wesley Kerr, MD, PhD – University of Pittsburgh Neurology
Rationale:
Cenobamate has shown efficacy in treating focal seizures, with high response rates for focal to bilateral tonic-clonic seizures. A previous post-hoc analysis of survival in a clinical trial cohort showed that the all-cause standardized mortality ratio (SMR) for cenobamate-treated patients was 1.32 (95% CI: 0.84-2.0), which was not significantly different from the general population. The present real-world study examined the all-cause mortality rate in patients after initiating cenobamate vs the mortality rate in patients treated with selected antiseizure medications (ASMs) that have similar patterns of use in medication-resistant epilepsy.Methods:
A retrospective observational study using de-identified electronic health records from 28 US health systems (Truveta) identified adults (≥18 years) with an epilepsy diagnosis who initiated therapeutic doses of cenobamate or another selected ASM (brivaracetam, clobazam, lacosamide, eslicarbazepine, or perampanel) between 1/1/2020-12/5/2024. New initiations were identified with at least a 1-year washout. Patients were included if they remained on treatment for ≥90 days after initiation. Patients with an epilepsy-related emergency room visit or inpatient admission in the previous 6 months were excluded. Mortality rates were examined for cenobamate and the comparator ASMs with SMRs to account for age, sex, race, ethnicity, and year; and Cox proportional hazards to account for epilepsy characteristics, comorbidities, and healthcare utilization. A sensitivity analysis used propensity matching (4:1 ratio) to account for differences in patients who initiated cenobamate. Results:
A total of 3184 patients (51.4% female; mean age 44.8 years) were included. In the overall cohort (n=634 cenobamate; n=2550 other ASMs), 4 and 88 deaths occurred in the cenobamate and comparator ASM groups, respectively; in the propensity-matched cohort (n=361 cenobamate, n=1444 other ASMs), 2 and 36 deaths occurred, respectively. Patients who initiated cenobamate had a mortality rate indistinguishable from that of the general population (SMR 0.69, 95% CI: 0.014-1.37). Patients who initiated comparator ASMs had a higher-than-expected mortality rate (SMR 1.97, 95% CI: 1.56-2.39). Similar findings were observed after propensity matching (cenobamate SMR 0.56, 95% CI: 0.01-1.34; comparator ASMs SMR 2.03, 95% CI: 1.37-2.70). When evaluated using a Cox proportional hazards model, cenobamate was associated with a 68% reduction in mortality rate compared to the other ASMs (HR 0.32, 95% CI: 0.12-0.92; P=0.04). After propensity matching, the comparative reduction in mortality rate with cenobamate was maintained (69% reduction; HR 0.31, 95% CI: 0.08-1.32; P=0.11).Conclusions:
This retrospective analysis shows that patients treated with cenobamate at therapeutic doses had lower mortality rates than patients treated with selected comparable ASMs commonly used for medication-resistant epilepsy. Further exploration of these results are needed to compare to other ASMs and non-ASM treatment options (e.g., surgery and neuromodulation), to compare to patients who were excluded from this study, and to evaluate the mechanisms of these associations.Funding:
Funded by SK Life Science, Inc.