PMID- 34093420 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210608 IS - 1664-2295 (Print) IS - 1664-2295 (Electronic) IS - 1664-2295 (Linking) VI - 12 DP - 2021 TI - Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome. PG - 673135 LID - 10.3389/fneur.2021.673135 [doi] LID - 673135 AB - Background: Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox-Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period. Material and Methods: Thirty centers were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg per day. Adverse effects and liver function tests were assessed after 2 weeks; 1, 3, and 6 months of treatment; and periodically thereafter. Seizure endpoints were the percentage of patients with >/=50 and 100% reduction in seizures compared to baseline. Results: A total of 93 patients were enrolled and included in the safety analysis. Eighty-two patients [27 (32.9%) DS, 55 (67.1%) LGS] with at least 3 months of treatment have been included in the effectiveness analysis; median previously failed antiseizure medications was eight. Pediatric and adult patients were uniformly represented in the cohort. At 3-month follow-up, compared to the 28-day baseline period, the percentage of patients with at least a 50% reduction in seizure frequency was 40.2% (plus 1.2% seizure-free). Retention rate was similar according to diagnosis, while we found an increased number of patients remaining under treatment in the adult group. CBD was mostly coadministered with valproic acid (62.2%) and clobazam (41.5%). In the safety dataset, 29 (31.2%) dropped out: reasons were lack of efficacy [16 (17.2%)] and adverse events (AEs) [12 (12.9%)], and one met withdrawal criteria (1.1%). Most reported AEs were somnolence (22.6%) and diarrhea (11.9%), followed by transaminase elevation and loss of appetite. Conclusions: CBD is associated with improved seizure control also in a considerable proportion of highly refractory patients with DS and LGS independently from clobazam use. Overall, CBD safety and effectiveness are not dose-related in this cohort. CI - Copyright (c) 2021 Iannone, Arena, Battaglia, Bisulli, Bonanni, Boni, Canevini, Cantalupo, Cesaroni, Contin, Coppola, Cordelli, Cricchiuti, De Giorgis, De Leva, De Rinaldis, d'Orsi, Elia, Galimberti, Morano, Granata, Guerrini, Lodi, La Neve, Marchese, Masnada, Michelucci, Nosadini, Pilolli, Pruna, Ragona, Rosati, Santucci, Spalice, Pietrafusa, Striano, Tartara, Tassi, Papa, Zucca, Russo, Mecarelli and The CBD LICE Italy Study Group. FAU - Iannone, Luigi Francesco AU - Iannone LF AD - Science of Health Department, School of Medicine, University Magna Graecia, Catanzaro, Italy. FAU - Arena, Gabriele AU - Arena G AD - Science of Health Department, School of Medicine, University Magna Graecia, Catanzaro, Italy. FAU - Battaglia, Domenica AU - Battaglia D AD - Pediatric Neurology, Department of Woman and Child Health and Public Health, Child Health Area, A. Gemelli University Polyclinic Foundation, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Catholic University of the Sacred Heart, Rome, Italy. FAU - Bisulli, Francesca AU - Bisulli F AD - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. AD - Epilepsy Center (Reference Center for Rare and Complex Epilepsies - EpiCARE), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. FAU - Bonanni, Paolo AU - Bonanni P AD - Epilepsy and Clinical Neurophysiology Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Eugenio Medea, Scientific Institute, Treviso, Italy. FAU - Boni, Antonella AU - Boni A AD - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. AD - Child Neuropsichiatry, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy. FAU - Canevini, Maria Paola AU - Canevini MP AD - Department of Health Sciences, Epilepsy Center, San Paolo Hospital, University of Milan, Milan, Italy. FAU - Cantalupo, Gaetano AU - Cantalupo G AD - Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy. FAU - Cesaroni, Elisabetta AU - Cesaroni E AD - Child Neurology and Psychiatry Unit, G. Salesi Children's Hospital-University of Ancona, Ancona, Italy. FAU - Contin, Manuela AU - Contin M AD - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. AD - Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy. FAU - Coppola, Antonietta AU - Coppola A AD - Department of Neuroscience, Reproductive, and Odontostomatological Sciences, Epilepsy Centre, University of Naples Federico II, Naples, Italy. FAU - Cordelli, Duccio Maria AU - Cordelli DM AD - IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'eta Pediatrica, Bologna, Italy. FAU - Cricchiuti, Giovanni AU - Cricchiuti G AD - Department of Pediatrics, Epilepsy Center, Institute of Medicine, University Hospital of Udine, Udine, Italy. FAU - De Giorgis, Valentina AU - De Giorgis V AD - Department of Child Neurology and Psychiatry, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy. FAU - De Leva, Maria Fulvia AU - De Leva MF AD - Pediatric Neurology, Department of Neuroscience, Santobono-Pausilipon Children's Hospital, Naples, Italy. FAU - De Rinaldis, Marta AU - De Rinaldis M AD - Unit for Severe Disabilities in Developmental Age and Young Adults (Developmental Neurology and Neurorehabilitation), Scientific Institute Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) "E. Medea", Brindisi, Italy. FAU - d'Orsi, Giuseppe AU - d'Orsi G AD - Epilepsy Centre - Clinic of Nervous System Diseases, Riuniti Hospital, Foggia, Italy. FAU - Elia, Maurizio AU - Elia M AD - Oasi Research Institute Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Troina, Italy. FAU - Galimberti, Carlo Andrea AU - Galimberti CA AD - Epilepsy Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy. FAU - Morano, Alessandra AU - Morano A AD - Neurology Unit, Department of Human Neurosciences, "Sapienza" University, Rome, Italy. FAU - Granata, Tiziana AU - Granata T AD - Department of Pediatric Neuroscience, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan, Italy. FAU - Guerrini, Renzo AU - Guerrini R AD - Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, A. Meyer Children's Hospital, Florence, Italy. FAU - Lodi, Monica A M AU - Lodi MAM AD - Pediatric Neurology Unit, Epilepsy Center, Department of Neuroscience, "Fatebenefratelli e Oftalmico" Hospital, Milan, Italy. FAU - La Neve, Angela AU - La Neve A AD - Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. FAU - Marchese, Francesca AU - Marchese F AD - Pediatric Neurology and Muscular Diseases Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) 'G. Gaslini' Institute, Genoa, Italy. AD - Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal, and Child Health, University of Genoa, Genoa, Italy. FAU - Masnada, Silvia AU - Masnada S AD - Department of Pediatric Neurology, V. Buzzi Children's Hospital, Milan, Italy. FAU - Michelucci, Roberto AU - Michelucci R AD - Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna, Unit of Neurology, Bellaria Hospital, Bologna, Italy. FAU - Nosadini, Margherita AU - Nosadini M AD - Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy. FAU - Pilolli, Nicola AU - Pilolli N AD - Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. FAU - Pruna, Dario AU - Pruna D AD - Pediatric Neurology and Epileptology Unit, Brotzu Hospital Trust, Cagliari, Italy. FAU - Ragona, Francesca AU - Ragona F AD - Department of Pediatric Neuroscience, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan, Italy. FAU - Rosati, Anna AU - Rosati A AD - Pediatric Neurology, Neurogenetics, and Neurobiology Unit and Laboratories, A. Meyer Children's Hospital, Florence, Italy. FAU - Santucci, Margherita AU - Santucci M AD - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. AD - Child Neuropsichiatry, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy. FAU - Spalice, Alberto AU - Spalice A AD - Child Neurology Division, Department of Pediatrics, Sapienza University of Rome, Rome, Italy. FAU - Pietrafusa, Nicola AU - Pietrafusa N AD - Neurology Unit, Department of Neurosciences (N.S., M.T.), Bambino Gesu Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy. FAU - Striano, Pasquale AU - Striano P AD - Pediatric Neurology and Muscular Diseases Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) 'G. Gaslini' Institute, Genoa, Italy. AD - Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal, and Child Health, University of Genoa, Genoa, Italy. FAU - Tartara, Elena AU - Tartara E AD - Epilepsy Center, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy. FAU - Tassi, Laura AU - Tassi L AD - Claudio Munari" Epilepsy Surgery Centre, Azienda Socio Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Papa, Amanda AU - Papa A AD - Child Neuropsychiatry Department, Maggiore della Carita University Hospital, Novara, Italy. FAU - Zucca, Claudio AU - Zucca C AD - Clinical Neurophysiology Unit, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Eugenio Medea, Scientific Institute, Lecco, Italy. FAU - Russo, Emilio AU - Russo E AD - Science of Health Department, School of Medicine, University Magna Graecia, Catanzaro, Italy. FAU - Mecarelli, Oriano AU - Mecarelli O AD - Department of Human Neurosciences, Sapienza University, Rome, Italy. CN - CBD LICE Italy Study Group LA - eng PT - Journal Article DEP - 20210520 PL - Switzerland TA - Front Neurol JT - Frontiers in neurology JID - 101546899 PMC - PMC8173151 OTO - NOTNLM OT - Dravet syndrome OT - cannabidiol OT - epilepsy OT - expanded access program OT - lennox-gastaut syndrome COIS- FB has participated in clinical trials for GW Pharmaceuticals; received research grants, speaker fees or participated to advisory boards for Eisai, Cyberonics, UCB Pharma and Bial. MPC Canevini has participated advisory boards and/or received research fundings from UCB Pharma, Eisai, Italfarmaco, Cyberonics, Novartis, and the European Union. AC has received speaker fees by Eisai. CB has received speaker fees from Eisai, UCB Pharma, FB Health and Sandoz. Gd'O has served on the advisory board of Eisai. CG has received research grants and/or speaker fees from UCB Pharma, Eisai and Bial. TG received a speaker fee from GW Pharmaceuticals. RG has received consulting fees and speaker honoraria from Zogenix, Biomarin, UCB, Eisai, Novartis, GW Pharma, and Biocodex. OM has received consulting fees and speaker honoraria by Bial, Eisai, GW Pharmaceuticals and UCB Pharma. AL has received speaker's or consultancy fees from Eisai, Mylan, Sanofi, Bial, GW Pharmaceuticals and UCB Pharma. PP received speaker's fees from Eisai and UCB Pharma. AR received consulting fees from GW Pharmaceuticals. ER has received speaker fees and/or fundings and has participated in advisory boards for Eisai, Pfizer, GW Pharmaceuticals, UCB Pharma, Arvelle Therapeutics. NS has received grant support and fees for advisory board participation from GW Pharmaceuticals. PS developed within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (legge 232 del 2016) and received speaker fees and participated at advisory boards for Biomarin, Zogenyx, GW Pharmaceuticals, Neuraxpharma; he also received research funding by ENECTA BV, GW Pharmaceuticals, Kolfarma srl., Eisai. ET has received speaker's fees from Eisai and Sandoz. AV received speaker's fees from Eisai, Italfarmaco, and GW Pharmaceuticals. MV received speaker's fees from Eisai and GW Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/06/08 06:00 MHDA- 2021/06/08 06:01 PMCR- 2021/05/20 CRDT- 2021/06/07 05:50 PHST- 2021/02/26 00:00 [received] PHST- 2021/03/31 00:00 [accepted] PHST- 2021/06/07 05:50 [entrez] PHST- 2021/06/08 06:00 [pubmed] PHST- 2021/06/08 06:01 [medline] PHST- 2021/05/20 00:00 [pmc-release] AID - 10.3389/fneur.2021.673135 [doi] PST - epublish SO - Front Neurol. 2021 May 20;12:673135. doi: 10.3389/fneur.2021.673135. eCollection 2021.