Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study
Por:
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, Domínguez-Carral J, Ramírez-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 and Coppola, A
Publicada:
1 jul 2025
Ahead of Print:
1 mar 2025
Resumen:
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.
Filiaciones:
Irelli, EC:
Sapienza Univ, Dept Human Neurosci, Viale Univ 30, I-00185 Rome, Italy
Mazzeo, A:
Sapienza Univ, Dept Human Neurosci, Viale Univ 30, I-00185 Rome, Italy
Caraballo, RH:
Hosp Pediat Prof Dr Juan P Garrahan, Dept Neurol, Buenos Aires, Argentina
Perulli, M:
Fdn Policlin Univ Agostino Gemelli IRCCS, Pediat Neurol Unit, Rome, Italy
Moloney, PB:
Mater Misericordiae Univ Hosp, Dept Neurol, Dublin, Ireland
Pena-Ceballos, J:
Beaumont Hosp, Dept Neurol, Dublin, Ireland
Rubino, M:
Federico II Univ Naples, Dept Neurosci Reprod Sci & Odontostomatol, Via Pansini 5, I-80131 Naples, Italy
Mieszczanek, KM:
Danish Epilepsy Ctr, Dianalund, Denmark
Santangelo, A:
Univ Pisa, Dept Clin & Expt Med, Pisa, Italy
Licchetta, L:
IRCCS, Bologna, Italy
De Giorgis, V:
Univ Pavia, Dept Brain & Behav Sci, Pavia, Italy
IRCCS, Mondino Fdn, Epilepsy Ctr, Pavia, Italy
Valenzuela, GR:
Hosp Pediat Prof Dr Juan P Garrahan, Dept Neurol, Buenos Aires, Argentina
Casellato, S:
Univ Sassari, Azienda Osped Univ, Ctr Pediat Epilepsies, Child Neuropsychiat Unit,Dept Womans & Childs Hlth, Sassari, Italy
Cesaroni, E:
Azienda Osped Univ Marche, Pediat Hosp G Salesi, Child Neurol & Psychiat Unit, Ancona, Italy
Operto, FF:
Univ Catanzaro, Sch Med, Sci Hlth Dept, Catanzaro, Italy
Domínguez-Carral J:
Inst Recerca Sant Joan Deu, Epilepsy Unit, Dept Child Neurol, Barcelona, Spain
Ramírez-Camacho A:
Inst Recerca Sant Joan Deu, Epilepsy Unit, Dept Child Neurol, Barcelona, Spain
Ferretti, A:
Sapienza Univ, Fac Med & Psychol, Dept Neurosci Mental Hlth & Sense Organs NESMOS, Rome, Italy
Santangelo, G:
Azienda Rilievo Nazl ad Alta Sspecializzaz, Child Neuropsychiat Dept, Itituto Mediterraneo Eccellenza Pediat, Via Benedettini, I-90100 Palermo, Italy
Aledo-Serrano, A:
Vithas La Milagrosa Univ Hosp, Vithas Hosp Grp, Epilepsy & Neurogenet Unit, Madrid, Spain
Rueegger, A:
Univ Childrens Hosp, Dept Neuropediat, Zurich, Switzerland
Mancardi, MM:
IRCCS Ist Giannina Gaslini, Genoa, Italy
Prato, G:
IRCCS Ist Giannina Gaslini, Genoa, Italy
Riva, A:
Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy
Bergonzini, L:
IRCCS, Bologna, Italy
Cordelli, DM:
IRCCS, Bologna, Italy
Bonanni, P:
Sci Inst Res Hospitalizat & Healthcare, Sci Inst, E Medea, Conegliano, Italy
Bisulli, F:
IRCCS, Bologna, Italy
Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy
Di Gennaro, G:
Ist Ricovero & Cura Carattere Sci Neuromed, Pozzilli, Italy
Matricardi, S:
Univ G D Annunziodi Chieti Pescara, Chieti, Italy
Striano, P:
IRCCS Ist Giannina Gaslini, Genoa, Italy
Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy
Delanty, N:
Beaumont Hosp, Dept Neurol, Dublin, Ireland
Royal Coll Surgeons Ireland, Sch Pharm & Biomol Sci, Dublin, Ireland
FutureNeuro Res Ctr, Dublin, Ireland
Marini, C:
Azienda Osped Univ Marche, Pediat Hosp G Salesi, Child Neurol & Psychiat Unit, Ancona, Italy
Battaglia, D:
Fdn Policlin Univ Agostino Gemelli IRCCS, Pediat Neurol Unit, Rome, Italy
Di Bonaventura, C:
Sapienza Univ, Dept Human Neurosci, Viale Univ 30, I-00185 Rome, Italy
Ramantani, G:
Univ Childrens Hosp, Dept Neuropediat, Zurich, Switzerland
Gardella, E:
Danish Epilepsy Ctr, Dianalund, Denmark
Univ Southern Denmark, Odense, Denmark
Orsini, A:
Univ Pisa, Dept Clin & Expt Med, Pisa, Italy
Coppola, A:
Federico II Univ Naples, Dept Neurosci Reprod Sci & Odontostomatol, Via Pansini 5, I-80131 Naples, Italy
Green Submitted, Green Published, hybrid
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