Real-world comparison of first-line antiseizure monotherapy and the role of age at treatment initiation in newly diagnosed childhood epilepsy: A cohort study from a tertiary center.

Abstract

Objective: This study was undertaken to evaluate the real-world effectiveness and tolerability of first-line antiseizure medication (ASM) monotherapy in children with newly diagnosed epilepsy, focusing on comparative outcomes across developmental age groups and ASM types, and identifying clinical risk factors of treatment failure.

Methods: This retrospective cohort study analyzed 10 years of electronic medical records from Shenzhen Children's Hospital. Children aged ≤18 years who initiated monotherapy with one of five ASMs (oxcarbazepine, valproate, levetiracetam, topiramate, or lamotrigine) were included. The primary outcome was treatment success, defined as sustained seizure and side effect freedom at the defined analytic endpoint. Outcomes based on the 2010 International League Against Epilepsy (ILAE) definition were also evaluated. Nineteen clinical variables across six domains were analyzed. Multivariable Cox regression and stabilized inverse probability of treatment weighting were used to adjust for confounding.

Results: Among 7060 eligible patients with a median follow-up of 14.0 months, 47.9% achieved treatment success, and 48.3% met ILAE criteria. The median seizure- and side effect-free survival was 24.8 months (95% confidence interval [CI] = 23.3-26.5 months). Oxcarbazepine (32.3%), valproate (31.7%), and levetiracetam (22.5%) were the most commonly prescribed ASMs. Treatment success did not differ significantly across ASM types or age groups. Epileptic spasms (hazard ratio [HR] = 2.86, 95% CI = 1.98-4.09), generalized seizures (HR = 1.78, 95% CI = 1.49-2.13), seizures before reaching maintenance dose (HR = 1.52, 95% CI = 1.37-1.70), delayed treatment initiation (HR ~ 1.30), and neurodevelopmental delay (HR = 1.42, 95% CI = 1.26-1.60) were significant risk factors of treatment failure.

Significance: First-line ASMs showed similar effectiveness in routine pediatric care. Childhood epilepsy treatment outcomes were more strongly influenced by seizure characteristics, neurodevelopmental comorbidities, and timing of initiation than by ASM choice or age. These findings support extrapolating ASM efficacy across pediatric age groups and highlight the value of real-world evidence in treatment decision-making.