Dravet syndrome seizure frequency and clustering: Placebo-treated patients in clinical trials.

Dravet syndrome is a rare developmental epilepsy syndrome associated with severe, treatment-resistant seizures. Since seizures and seizure clusters are linked to morbidity, reduced quality of life, and premature mortality, a greater understanding of these outcomes could improve trial designs. This analysis explored seizure types, seizure clusters, and factors affecting seizure cluster variability in Dravet syndrome patients. Pooled post-hoc analyses were performed on data from placebo-treated patients in GWPCARE 1B and GWPCARE 2 randomized controlled phase III trials comparing cannabidiol and placebo in Dravet syndrome patients aged 2-18 years. Multivariate stepwise analysis of covariance of log-transformed convulsive seizure cluster frequency was performed, body weight and body mass index z-scores were calculated, and incidence of adverse events was assessed. Data were summarized in three age groups. We analyzed 124 placebo-treated patients across both studies (2-5 years: n = 35; 6-12 years: n = 52; 13-18 years: n = 37). Generalized tonic-clonic seizures followed by myoclonic seizures were the most frequent seizure types. Mean and median convulsive seizure cluster frequency overall decreased between baseline and maintenance period but did not change significantly during the latter; variation in convulsive seizure cluster frequency was observed across age groups. Multivariate analysis suggested correlations between convulsive seizure cluster frequency and age (positive), and body mass index (BMI) (negative). Post-hoc analyses suggested that potential relationships could exist between BMI, age and convulsive seizure cluster variation. Results suggested that seizure cluster frequency may be a valuable outcome in future trials. Further research is needed to confirm our findings.

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest This study was funded by Jazz Pharmaceuticals. Editorial and medical writing services were provided by Costello Medical. RN: Received compensation for consulting work and/or attending Scientific Advisory Boards from GW Pharma, LivaNova, Lundbeck, Marinus, Stoke, Supernus, Advicenne, Takeda, UCB Inc., Servier, Eisai, Ionis, Zogenix, Neuraxpharm. She has research grants from European FP7 program, European joint program on rare diseases; KH, RL, CN: Employees of Jazz Pharmaceuticals; OD: Receives grant support from NINDS, NIMH, MURI, CDC and NSF. He has equity and/or compensation from the following companies: Tilray, Receptor Life Sciences, Qstate Biosciences, Hitch Biosciences, Tevard Biosciences, Empatica, SilverSpike, and California Cannabis Enterprises (CCE). He has received consulting fees from Zogenix, Ultragenyx, BridgeBio, and Marinus. He holds patents for the use of cannabidiol in treating neurological disorders but these are owned by Jazz Pharmaceuticals and he has waived any financial interests. He holds other patents in molecular biology.