| Title: |
Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study |
| Authors: |
Cerulli Irelli, Emanuele; Mazzeo, Adolfo; Caraballo, Roberto H; Perulli, Marco; Moloney, Patrick B; Peña-Ceballos, Javier; Rubino, Marica; Mieszczanek, Katarzyna M; Santangelo, Andrea; Licchetta, Laura; De Giorgis, Valentina; Reyes Valenzuela, Gabriela; Casellato, Susanna; Cesaroni, Elisabetta; Operto, Francesca F; Domínguez-Carral, Jana; Ramírez-Camacho, Alia; Ferretti, Alessandro; Santangelo, Giuseppe; Aledo-Serrano, Angel; Rüegger, Andrea; Mancardi, Maria M; Prato, Giulia; Riva, Antonella; Bergonzini, Luca; Cordelli, Duccio M; Bonanni, Paolo; Bisulli, Francesca; Di Gennaro, Giancarlo; Matricardi, Sara; Striano, Pasquale; Delanty, Norman; Marini, Carla; Battaglia, Domenica; Di Bonaventura, Carlo; Ramantani, Georgia; Gardella, Elena; Orsini, Alessandro; Coppola, Antonietta |
| Contributors: |
Cerulli Irelli, Emanuele; Mazzeo, Adolfo; Caraballo, Roberto H; Perulli, Marco; Moloney, Patrick B; Peña-Ceballos, Javier; Rubino, Marica; Mieszczanek, Katarzyna M; Santangelo, Andrea; Licchetta, Laura; De Giorgis, Valentina; Reyes Valenzuela, Gabriela; Casellato, Susanna; Cesaroni, Elisabetta; Operto, Francesca F; Domínguez-Carral, Jana; Ramírez-Camacho, Alia; Ferretti, Alessandro; Santangelo, Giuseppe; Aledo-Serrano, Angel; Rüegger, Andrea; Mancardi, Maria M; Prato, Giulia; Riva, Antonella; Bergonzini, Luca; Cordelli, Duccio M; Bonanni, Paolo; Bisulli, Francesca; Di Gennaro, Giancarlo; Matricardi, Sara; Striano, Pasquale; Delanty, Norman; Marini, Carla; Battaglia, Domenica; Di Bonaventura, Carlo; Ramantani, Georgia; Gardella, Elena; Orsini, Alessandro; Coppola, Antonietta |
| Publisher Information: |
John Wiley and Sons Inc; Hoboken, NJ |
| Publication Year: |
2025 |
| Collection: |
Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: |
CBD; Lennox–Gastaut syndrome; developmental and epileptic encephalopathy; effectivene; epilepsy; intellectual disability |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40126049; info:eu-repo/semantics/altIdentifier/wos/WOS:001450348700001; volume:Online ahead of print; firstpage:1; lastpage:15; numberofpages:15; journal:EPILEPSIA; https://hdl.handle.net/11573/1735822 |
| DOI: |
10.1111/epi.18378 |
| Availability: |
https://hdl.handle.net/11573/1735822; https://doi.org/10.1111/epi.18378 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.7DDC2B6C |
| Database: |
BASE |