Real-world retention of newer antiseizure medications in children with epilepsy - a nationwide study

BackgroundChildren with epilepsy are rarely included in clinical drug trials, delaying approval and introduction of new antiseizure medications (ASMs). To circumvent this we used population-wide register data to study retention, an intergrated meassure of effect and tolerability, of newer ASMs used in children in Sweden; brivaracetam, cenobamate, lacosamide, and perampanel. MethodsAll cases of incident epilepsy and subsequent ASM treatment 2007-2021 were identified using national registers. Retention rates of newer ASMs were calculated using Kaplan-Meier analyses. Cox regression was used to investigate how factors associated with therapy-resistant epilepsy affected risk of discontinuing each drug and to compare the risk of discontinuing each of the newer ASMs to levetiracetam, the most common ASM, in patients matched for age at epilepsy onset and number of previously tried ASMs. ResultsOut of 16431 included 54% were male, median age 7 years [Q1-Q3:3-12]. Developmental or intellectual disorders, followed by neurological malformations, were the most common comorbidities. In 2023 [~]10% of all ongoing treatments started <18years were brivaracetam, cenobamate, lacosamide, or perampanel. Brivaracetam, cenobamate, and lacosamide were all used off-label before authorization in children. Brivaracetam had the highest three-year retention of all antiseizure medications, 67%(95%CI:60-76) for the whole cohort, lacosamide and lamotrigine the highest five-year retentions: 40%(95%CI:36-45) and 45%(95%CI:43-46). perampanel had the lowest four-year retention. Retentions in the youngest were modest. In those 1-5years brivaracetam had among the highest three-year retention: 64%(95%CI:52-79), followed by lamotrigine and valproate. Lacosamide and lamotrigine had the highest five-year retentions: 40%(95%CI:33-49) and 42%(95%CI:39-44). Brivaracetam had the highest of all three-year retentions in those 6-11: 74%(95%CI:63-87) and lacosamide among the highest five-year retentions: 48%(95%CI:40-57), together with lamotrigine. In the eldest brivaracetam and lamotrigine had the highest retentions: 68%(95%CI:51-91) and 62%(95%CI:60-64), lacosamide had lower five-year retention than levetiracetam and lamotrigine. In Cox regression users of newer antiseizure medications, age-matched to levetiracetam-users with equal number previous antiseizure medications, the hazard ratio for discontinuing brivaracetam was 0.5(95%CI:0.4-0.8), perampanel 2.0(95%CI:1.2-3.2), and lacosamide 1.0(95%CI:0.8-1.2). ConclusionBrivaracetam show higher or similar retention and lacosamide similar retention as levetiracetam and lamotrigine, suggesting these could be treatment options in early epilepsy. Off-label use is common stressing the need for pediatric clinical trials.