PMID- 36327646
OWN - NLM
STAT- MEDLINE
DCOM- 20221129
LR  - 20230104
IS  - 1525-5069 (Electronic)
IS  - 1525-5050 (Linking)
VI  - 137
IP  - Pt A
DP  - 2022 Dec
TI  - Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in 
      pediatric and adult patients with epilepsy.
PG  - 108958
LID - S1525-5050(22)00407-3 [pii]
LID - 10.1016/j.yebeh.2022.108958 [doi]
AB  - AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in 
      patients with developmental and epileptic encephalopathies, including Dravet 
      syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access 
      Program (EAP). METHODS: This was a multicenter, retrospective, observational 
      study of patients treated with purified CBD in 14 hospitals across Spain. 
      Patients with (1) written informed consent and (2) at least 6 months follow-up 
      before the closure of the database were included. Primary effectiveness endpoints 
      included reductions (100 %, >/=75 %, >/=50 %, >/=25 %, or 0 %) or worsening in seizure 
      frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 
      12-month visits and at the last visit, and median relative seizure reduction 
      between baseline and last visit. Secondary effectiveness endpoints included 
      retention rate, reduction in seizure severity, status epilepticus, healthcare 
      utilization, and quality of life. Primary safety endpoints included rates of 
      adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and 
      two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age 
      of 15.9 years were enrolled. Patients were highly refractory to antiseizure 
      medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean 
      CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with 
      >/=50 % reduction in the total number of seizures from baseline was 44.9 % at 
      6 months and 38.9 % at 12 months. The median number of total seizures per month 
      reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity 
      was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). 
      Quality of life, based on the CAVE scale, increased from a mean score of 
      17.9 +/- 4.7 (n = 54) at baseline to 21.7 +/- 5.5 (n = 51) at the last patient visit 
      (21.2 % improvement). The mean treatment retention time was 10.3 months. There 
      were no statistically significant changes in the number of status epilepticus 
      episodes, but lower healthcare utilization was observed. Adverse events occurred 
      in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) 
      and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 
      7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were 
      considered together. CONCLUSIONS: Cannabidiol demonstrated promising 
      effectiveness and tolerability in patients with developmental and epileptic 
      encephalopathies taking part in a Spanish EAP.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Villanueva, Vicente
AU  - Villanueva V
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain. Electronic address: 
      villanueva_vichab@gva.es.
FAU - Garcia-Ron, Adrian
AU  - Garcia-Ron A
AD  - Hospital Clinico Universitario, Madrid, Spain.
FAU - Smeyers, Patricia
AU  - Smeyers P
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Arias, Eva
AU  - Arias E
AD  - Hospital Clinico Universitario, Madrid, Spain.
FAU - Soto, Victor
AU  - Soto V
AD  - Hospital Universitario Nino Jesus, Madrid, Spain.
FAU - Garcia-Penas, Juan Jose
AU  - Garcia-Penas JJ
AD  - Hospital Universitario Nino Jesus, Madrid, Spain.
FAU - Gonzalez-Alguacil, Elena
AU  - Gonzalez-Alguacil E
AD  - Hospital Universitario Nino Jesus, Madrid, Spain.
FAU - Sayas, Debora
AU  - Sayas D
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Serrano-Castro, Pedro
AU  - Serrano-Castro P
AD  - Hospital Regional Universitario Malaga, Malaga, Spain.
FAU - Garces, Mercedes
AU  - Garces M
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Hampel, Kevin
AU  - Hampel K
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Tomas, Miguel
AU  - Tomas M
AD  - Hospital Universitario y Politecnico La Fe, Valencia, Spain.
FAU - Lara, Julian
AU  - Lara J
AD  - Hospital Universitario Puerta de Hierro, Madrid, Spain.
FAU - de Toledo, Maria
AU  - de Toledo M
AD  - Hospital Universitario La Princesa, Madrid, Spain.
FAU - Barcelo, Ines
AU  - Barcelo I
AD  - Hospital Universitario Son Espases, Palma de Mallorca, Spain.
FAU - Aledo-Serrano, Angel
AU  - Aledo-Serrano A
AD  - Hospital Ruber Internacional, Madrid, Spain.
FAU - Gil-Nagel, Antonio
AU  - Gil-Nagel A
AD  - Hospital Ruber Internacional, Madrid, Spain.
FAU - Iacampo, Lucas
AU  - Iacampo L
AD  - Hospital Universitario de Canarias en Tenerife, Spain.
FAU - Falip, Merce
AU  - Falip M
AD  - Hospital Universitario Bellvitge, Barcelona, Spain.
FAU - Saiz-Diaz, Rosa Ana
AU  - Saiz-Diaz RA
AD  - Hospital Universitario 12 de Octubre, Madrid, Spain.
FAU - Gomez-Ibanez, Asier
AU  - Gomez-Ibanez A
AD  - Clinica Universidad Navarra, Pamplona/Madrid, Spain.
FAU - Sopelana, David
AU  - Sopelana D
AD  - Complejo Hospitalario Universitario, Albacete, Spain.
FAU - Sanchez-Larsen, Alvaro
AU  - Sanchez-Larsen A
AD  - Complejo Hospitalario Universitario, Albacete, Spain.
FAU - Lopez-Gonzalez, Francisco Javier
AU  - Lopez-Gonzalez FJ
AD  - Complejo Hospitalario Universitario Santiago, Santiago de Compostela, Spain.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20221029
PL  - United States
TA  - Epilepsy Behav
JT  - Epilepsy & behavior : E&B
JID - 100892858
RN  - 19GBJ60SN5 (Cannabidiol)
RN  - 0 (Anticonvulsants)
RN  - CDKL5 deficiency disorder
SB  - IM
MH  - Adult
MH  - Child
MH  - Humans
MH  - Adolescent
MH  - *Cannabidiol/therapeutic use
MH  - Anticonvulsants/therapeutic use
MH  - Retrospective Studies
MH  - Quality of Life
MH  - *Epilepsy/drug therapy/chemically induced
MH  - *Lennox Gastaut Syndrome/drug therapy
MH  - Seizures/drug therapy
MH  - *Epilepsies, Myoclonic/drug therapy
MH  - *Status Epilepticus/drug therapy
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Dravet syndrome
OT  - Lennox-Gastaut syndrome
OT  - Real-world evidence
COIS- Declaration of Competing Interest V Villanueva has received honoraria and/or 
      research funds from Angelini Pharma, Bial, Eisai, GW Pharmaceutical Company (now 
      a part of Jazz Pharmaceuticals), Neuraxpharm, Novartis, Nutricia, Takeda, UCB 
      Pharma, and Zogenix. A Garcia-Ron has received consultant and speaker honoraria 
      from GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals). P Smeyers 
      has received fees for conferences and other educational activities from Eisai, GW 
      Pharmaceutical Company (now a part of Jazz Pharmaceuticals), Humana, Neuraxpharm, 
      and UCB. V Soto has received speaker honoraria from GW Pharmaceutical Company 
      (now a part of Jazz Pharmaceuticals). JJ Garcia-Penas has received consultant and 
      speaker honoraria from Bial, Eisai, GW Pharmaceutical Company (now a part of Jazz 
      Pharmaceuticals), Nutricia, Sanofi, UCB, and Zogenix. PJ. Serrano-Castro has 
      received consultant and/or speaker honoraria from Angelini-Pharma, Bial, Eisai, 
      GW Pharmaceuticals (now a part of Jazz Pharmaceuticals), Roche Pharmaceuticals, 
      UCB Pharma, and Zogenix Espana. A Aledo-Serrano has received funding for research 
      and educational activities from Angelini Pharma, Bial, Biocodex, Eisai, GW 
      Pharmaceutical Company (now a part of Jazz Pharmaceuticals), Neuraxpharm, PTC 
      Therapeutics, Sanofi, UCB, and Zogenix. A Gil-Nagel has received grants from Jazz 
      Pharmaceuticals, PTC Therapeutics and Zogenix, and received consultant and 
      speaker honoraria from Bial, Biocodex, Eisai, Esteve, HealthInCode,GW 
      Pharmaceutical Company (now a part of Jazz Pharmaceuticals), PTC Therapeutics, 
      Stoke, Synaptia,UCB Pharma,and Zogenix. A Gomez-Ibanez has received consultant 
      and speaker honoraria from GW Pharmaceutical Company (now a part of Jazz 
      Pharmaceuticals). M Falip has received consultant and speaker honoraria from GW 
      Pharmaceutical Company (now a part of Jazz Pharmaceuticals). F J Lopez-Gonzalez 
      has received consultant and speaker honoraria from Angelini Pharma, Bial, Eisai, 
      Esteve, GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals), LivaNova, 
      Nutricia, and UCB. E Arias, E Gonzalez-Alguacil, D Sayas, M Garces, K Hampel, M 
      Tomas, J Lara, M de Toledo, I Barcelo, L Iacampo, R Saiz-Diaz, D Sopelana, and A 
      Sanchez-Larsen have no conflicts of interest.
EDAT- 2022/11/04 06:00
MHDA- 2022/11/30 06:00
CRDT- 2022/11/03 19:20
PHST- 2022/07/15 00:00 [received]
PHST- 2022/10/12 00:00 [revised]
PHST- 2022/10/13 00:00 [accepted]
PHST- 2022/11/04 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/11/03 19:20 [entrez]
AID - S1525-5050(22)00407-3 [pii]
AID - 10.1016/j.yebeh.2022.108958 [doi]
PST - ppublish
SO  - Epilepsy Behav. 2022 Dec;137(Pt A):108958. doi: 10.1016/j.yebeh.2022.108958. Epub 
      2022 Oct 29.