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.

Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome / Francesco Iannone, Luigi; Arena, Gabriele; Battaglia, Domenica; Bisulli, Francesca; Bonanni, Paolo; Boni, Antonella; Paola Canevini, Maria; Cantalupo, Gaetano; Cesaroni, Elisabetta; Contin, Manuela; Coppola, Antonietta; Maria Cordelli, Duccio; Cricchiuti, Giovanni; De Giorgis, Valentina; Fulvia De Leva, Maria; De Rinaldis, Marta; D'Orsi, Giuseppe; Elia, Maurizio; Andrea Galimberti, Carlo; Morano, Alessandra; Granata, Tiziana; Guerrini, Renzo; M Lodi, Monica A; 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. - In: FRONTIERS IN NEUROLOGY. - ISSN 1664-2295. - 12:(2021), pp. 1-9. [10.3389/fneur.2021.673135]

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

Alessandra Morano;Tiziana Granata;Renzo Guerrini;Alberto Spalice;Oriano Mecarelli
2021

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 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.
2021
Dravet syndrome; cannabidiol; epilepsy; expanded access program; lennox-gastaut syndrome
01 Pubblicazione su rivista::01a Articolo in rivista
Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome / Francesco Iannone, Luigi; Arena, Gabriele; Battaglia, Domenica; Bisulli, Francesca; Bonanni, Paolo; Boni, Antonella; Paola Canevini, Maria; Cantalupo, Gaetano; Cesaroni, Elisabetta; Contin, Manuela; Coppola, Antonietta; Maria Cordelli, Duccio; Cricchiuti, Giovanni; De Giorgis, Valentina; Fulvia De Leva, Maria; De Rinaldis, Marta; D'Orsi, Giuseppe; Elia, Maurizio; Andrea Galimberti, Carlo; Morano, Alessandra; Granata, Tiziana; Guerrini, Renzo; M Lodi, Monica A; 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. - In: FRONTIERS IN NEUROLOGY. - ISSN 1664-2295. - 12:(2021), pp. 1-9. [10.3389/fneur.2021.673135]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1724380
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