Long-term CBD seizure response did not differ by genetic status in LGS

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a genetically heterogeneous developmental and epileptic encephalopathy in which variability in long-term cannabidiol (CBD) response remains incompletely understood. We evaluated whether long-term drop-seizure response trajectories to CBD differ according to genetic status. METHODS: This single-center retrospective longitudinal study analyzed systematically collected clinical follow-up data from 61 patients with LGS treated with pharmaceutical-grade CBD; 46 patients with ≥ 24 months of follow-up were included. Patients were classified as pathogenic/likely pathogenic variant-positive (PV+) or variant-negative (PV-). Drop-seizure reduction trajectories were assessed at 3-month intervals over 24 months. RESULTS: Drop-seizure reduction improved rapidly and was sustained over 24 months in both PV+ and PV- groups, with no significant differences between groups at the prespecified comparison time points. Longitudinal response trajectories showed substantial overlap, and sustained response was observed in 76.1% of patients. CONCLUSION: Long-term drop-seizure response to CBD in LGS was sustained but not stratified by genetic status, supporting a syndrome-level treatment approach irrespective of genetic findings.