Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study

Objective: This real-world, retrospective, multicenter study aims to investigate the effectiveness of highly purified cannabidiol (CBD) in a large cohort of patients with epilepsy of genetic etiology due to an identified monogenic cause. Additionally, we examine the potential relationship between sp...

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Detalles Bibliográficos
Autores: Irelli, EC, Mazzeo, A, Caraballo, RH, Perulli, M, Moloney, PB, Pena-Ceballos, J, Rubino, M, Mieszczanek, KM, Santangelo, A, Licchetta, L, De Giorgis, V, Valenzuela, GR, Casellato, S, Cesaroni, E, Operto, FF, Dominguez-Carral, J, Ramirez-Camacho, A, Ferretti, A, Santangelo, G, Aledo-Serrano, A, Rueegger, A, Mancardi, MM, Prato, G, Riva, A, Bergonzini, L, Cordelli, DM, Bonanni, P, Bisulli, F, Di Gennaro, G, Matricardi, S, Striano, P, Delanty, N, Marini, C, Battaglia, D, Di Bonaventura, C, Ramantani, G, Gardella, E, Orsini, A, Coppola, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p29353
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29353
Access Level:acceso abierto
Palabra clave:CBD
developmental and epileptic encephalopathy
effectiveness
epilepsy
intellectual disability
Lennox-Gastaut syndrome
Descripción
Sumario:Objective: This real-world, retrospective, multicenter study aims to investigate the effectiveness of highly purified cannabidiol (CBD) in a large cohort of patients with epilepsy of genetic etiology due to an identified monogenic cause. Additionally, we examine the potential relationship between specific genetic subgroups and treatment response. Methods: This study was conducted across 27 epilepsy centers and included patients with monogenic epileptic disorders (pathogenic or likely pathogenic variants) who were treated with highly purified CBD for at least 3 months. Results: A total of 266 patients (135 females, 50.8%) with monogenic epilepsies were included with a median age at CBD initiation of 12 years (interquartile range [IQR] = 7-19) and a median follow-up duration of 17 months (IQR = 12-24). Overall, 77 different monogenic epilepsies have been included, with the most common genes being SCN1A (32.3%), TSC2 (13.5%), CDKL5, and MECP2 (4.5% each). The mean seizure reduction at the last follow-up was 38.6%, with 47.5% of patients achieving >= 50% seizure reduction and 7.4% achieving seizure freedom. The Clinical Global Impression scale indicated improvement in 65.8% of patients. The general linear mixed model revealed that a shorter maximum duration of seizure freedom before CBD initiation and a higher degree of intellectual disability were independently associated with lower CBD effectiveness. Conversely, no significant differences in seizure outcome were observed across different epilepsy syndromes (Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex epilepsy, and other developmental and epileptic encephalopathy), between approved indications and off-label use, or between concomitant clobazam use or not. Significance: This study supports CBD as a potential treatment for monogenic epilepsies beyond its licensed indications, demonstrating comparable effectiveness between approved and off-label use and suggesting genetic subgroups with promising treatment responses.

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