Authors :
Presenting Author: Jianbin Mao, PhD – Cerevel Threrapeutics
Koji Takahashi, PhD – Cerevel Threrapeutics; Mu Cheng, MPH – Analysis Group; Churong Xu, MS – Analysis Group; Andra Boca, BS – Analysis Group; Yan Song, PhD – Analysis Group; Ann Dandurand, MD – Cerevel Threrapeutics
Rationale:
Despite the availability of more than 30 anti-seizure medications (ASMs), approximately thirty percent of people with focal onset epilepsy (FE) are drug resistant, defined per International League Against Epilepsy (ILAE) as failing two adequate, appropriate, and tolerated ASM regimens. There is a need to understand treatment patterns before and after patients becoming drug resistant in clinical practice, along with the adverse event (AE) profile and AE management for people living with drug-resistant FE.
Methods:
This retrospective, non-interventional chart study used subject-level data provided by 189 neurologists/epileptologists across US clinical practices. Eligible adults with confirmed diagnosis of drug-resistant FE, initiated a third line ASM therapy between January 2013 and January 2020 (i.e.,
the index date), and had medical history data available for ≥ one year prior to (
the baseline) and ≥ two years after the index date (
the follow-up).
Subjects who initiated cenobamate in their third line ASM did not have the ≥ two year follow-up requirement. ASM regimen, treatment duration, monotherapy vs combination therapy, number, and name of ASM agents were captured from first to fourth lines. As the initiation of third line indicated the emergence of drug resistance per ILAE definition, third line ASM regimen was of particular interest. Therefore, time to discontinuation, reasons for discontinuation, AE experience, and management were examined during third line. Descriptive statistics were used to analyze all variables except for “time to treatment discontinuation,” which was shown as Kaplan Meier survival curve.
Results:
The study included a total of 345 subjects, with an average (SD) age of 32.4 (11.2) years, 65.5% being male, and 78.3% being White/Caucasian. All subjects had at least three lines of ASM with first and secon lines during baseline, and third line during follow-up. A total of 187 subjects (54.2%) continued to fourth line. Treatment characteristics of these four lines of ASM were shown in Table 1. The top reasons for discontinuing third line were uncontrolled seizure and treatment intolerance/AEs, and the median time to discontinuation was 17.2 (95% confidence interval: 15.0, 23.9) months (Figure 1). A total of 132 (38.3%) subjects experienced at least one AE, with mean (SD) number of AEs per subject at 3.9 (4.1). The most common AEs were related to the central nervous system, manifesting as headache, somnolence, dizziness, and fatigue. Among the 132 subjects with at least one AE, 39.4%, 37.9%, 25.8%, 13.6% and 12.1% had dose adjustment, discontinuation of offending ASM, pharmacotherapy, emergency room visit and hospitalization, respectively. Conclusions:
This real-world study demonstrated that people living with drug-resistant FE in the US experience significant AEs, many of these AEs lead to dose adjustment, discontinuation, emergency room visit(s) and hospitalization(s).
Funding: This study was funded by Cerevel Therapeutics.