Epilepsia. 2021 Nov 23; doi: 10.1111/epi.17134. Epub 2021 Nov 23.
Long-term individual retention with cenobamate in adults with focal seizures: Pooled data from the clinical development program.
Epilepsia
Josemir W Sander, William E Rosenfeld, Jonathan J Halford, Bernhard J Steinhoff, Victor Biton, Manuel Toledo
Affiliations
Affiliations
- NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London, UK.
- Chalfont Centre for Epilepsy, Chalfont St. Peter, UK.
- Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands.
- Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, Missouri, USA.
- Comprehensive Epilepsy Center, Medical University of South Carolina, Charleston, South Carolina, USA.
- Department of Neurology and Clinical Neurophysiology, Kork Epilepsy Center, Kehl-Kork, Germany.
- Clinic for Neurology and Neurophysiology, Freiburg, Germany.
- Arkansas Epilepsy Program, Little Rock, Arkansas, USA.
- Epilepsy Unit, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
PMID: 34813673
DOI: 10.1111/epi.17134
Abstract
OBJECTIVE: We determined retention on open-label cenobamate therapy in the clinical development program to assess the long-term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures.
METHODS: Data from two randomized, controlled cenobamate studies and one open-label safety and pharmacokinetic study were pooled. Based on the percentage of participants remaining on treatment, retention rates were estimated using Kaplan-Meier survival analyses. We performed two additional analyses to assess factors contributing to retention, stratifying a robust data set (through 2 years) by cenobamate modal dose and frequently used concomitant anti-seizure medications. Cenobamate discontinuations and treatment-emergent adverse events were summarized.
RESULTS: Data from 1844 participants were pooled: 149 from a single-dose randomized trial, 355 from a multi-dose randomized trial, and 1340 from an open-label safety and pharmacokinetic study. Most participants from randomized trials continued in open-label extensions, and pooled data represent >95% of participants exposed to cenobamate. Baseline characteristics and disease and treatment histories were similar across studies. Median duration of cenobamate exposure was 34 months, with a median modal dose of 200 mg/day. Kaplan-Meier estimates of cumulative cenobamate retention rates were 80% at 1 year and 72% at 2 years. Once participants reached the maintenance phase, retention rates were consistently high in participants receiving ≥100 mg/day cenobamate, and concomitant anti-seizure medications did not affect long-term retention. By 2 years, 535 (29%) had actually discontinued cenobamate; the most common reasons for discontinuation were adverse events (37.6%), withdrawal of consent (21.1%), and other (16.8%).
SIGNIFICANCE: Treatment retention rates provide a proxy measure for long-term efficacy, safety, tolerability, and adherence. The consistently high retention rates we found suggest that cenobamate may be an effective and well-tolerated new treatment option for people with drug-resistant focal seizures.
© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Keywords: efficacy; epilepsy; open-label; retention rate; tolerability
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