TY - JOUR
T1 - Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox–Gastaut Syndrome
AU - Iannone, Luigi Francesco
AU - Arena, Gabriele
AU - Battaglia, Domenica Immacolata
AU - Bisulli, Francesca
AU - Bonanni, Paolo
AU - Boni, Antonella
AU - Canevini, Maria Paola
AU - Cantalupo, Gaetano
AU - Cesaroni, Elisabetta
AU - Contin, Manuela
AU - Coppola, Antonietta
AU - Cordelli, Duccio Maria
AU - Cricchiuti, Giovanni
AU - De Giorgis, Valentina
AU - De Leva, Maria Fulvia
AU - De Rinaldis, Marta
AU - D'Orsi, Giuseppe
AU - D'Orsi, Giovanni Maria
AU - Elia, Maurizio
AU - Galimberti, Carlo Andrea
AU - Morano, Alessandra
AU - Granata, Tiziana
AU - Guerrini, Renzo
AU - Lodi, Monica A. M.
AU - La Neve, Angela
AU - Marchese, Francesca
AU - Masnada, Silvia
AU - Michelucci, Roberto
AU - Nosadini, Margherita
AU - Pilolli, Nicola
AU - Pruna, Dario
AU - Ragona, Francesca
AU - Rosati, Anna
AU - Santucci, Margherita
AU - Spalice, Alberto
AU - Pietrafusa, Nicola
AU - Striano, Pasquale
AU - Tartara, Elena
AU - Tassi, Laura
AU - Papa, Amanda
AU - Zucca, Claudio
AU - Russo, Emilio
AU - Russo, Elisa
AU - Mecarelli, Oriano
PY - 2021
Y1 - 2021
N2 - 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.
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.
KW - Dravet syndrome
KW - cannabidiol
KW - epilepsy
KW - expanded access program
KW - lennox-gastaut syndrome
KW - Dravet syndrome
KW - cannabidiol
KW - epilepsy
KW - expanded access program
KW - lennox-gastaut syndrome
UR - http://hdl.handle.net/10807/197175
U2 - 10.3389/fneur.2021.673135
DO - 10.3389/fneur.2021.673135
M3 - Article
SN - 1664-2295
VL - 12
SP - 1
EP - 9
JO - Frontiers in Neurology
JF - Frontiers in Neurology
ER -