AUTHOR=Iannone Luigi Francesco , Arena Gabriele , Battaglia Domenica , Bisulli Francesca , Bonanni Paolo , Boni Antonella , Canevini Maria Paola , Cantalupo Gaetano , Cesaroni Elisabetta , Contin Manuela , Coppola Antonietta , Cordelli Duccio Maria , Cricchiuti Giovanni , De Giorgis Valentina , De Leva Maria Fulvia , De Rinaldis Marta , d'Orsi Giuseppe , Elia Maurizio , Galimberti Carlo Andrea , Morano Alessandra , Granata Tiziana , Guerrini Renzo , Lodi Monica A. M. , La Neve Angela , Marchese Francesca , Masnada Silvia , Michelucci Roberto , Nosadini Margherita , Pilolli Nicola , Pruna Dario , Ragona Francesca , Rosati Anna , Santucci Margherita , Spalice Alberto , Pietrafusa Nicola , Striano Pasquale , Tartara Elena , Tassi Laura , Papa Amanda , Zucca Claudio , Russo Emilio , Mecarelli Oriano ,  The CBD LICE Italy Study Group 

TITLE=Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox–Gastaut Syndrome

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.673135

DOI=10.3389/fneur.2021.673135

ISSN=1664-2295

ABSTRACT=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 centres were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg/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 8. Paediatric and adult patients were uniformly represented in the cohort. At 12 months follow-up (n = 51/82, 62.2%), compared to the 28-day baseline period, the percentage of patients with at least a 50% reduction in seizure frequency was 49.0% (3.9% 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 co-administered with valproic acid (62.2%) and clobazam (41.5%). In the safety dataset, twenty-nine (31.2%) dropped out: reasons were lack of efficacy (16 [17.2%]), AEs (12 [12.9%]) and 1 met withdrawal criteria (1.1%). Most reported AEs were somnolence (22.6%) and diarrhoea (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.