TY - JOUR
T1 - Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes
AU - Devinsky, Orrin
AU - Verducci, Chloe
AU - Thiele, Elizabeth A.
AU - Laux, Linda C.
AU - Patel, Anup D.
AU - Filloux, Francis
AU - Szaflarski, Jerzy P.
AU - Wilfong, Angus
AU - Clark, Gary D.
AU - Park, Yong D.
AU - Seltzer, Laurie E.
AU - Bebin, E. Martina
AU - Flamini, Robert
AU - Wechsler, Robert T.
AU - Friedman, Daniel
N1 - Funding Information:
GW Pharmaceuticals provided study drug, collected and collated the data from all sites, produced standard set of data tables, and sent all results directly to Orrin Devinsky for analysis and interpretation by authors. Open access fees were funded by Greenwich Biosciences. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Publisher Copyright:
© 2018 The Authors
PY - 2018/9
Y1 - 2018/9
N2 - Objective: We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. Methods: We included patients aged 1–30 years with severe childhood-onset epilepsy who received CBD for ≥10 weeks as part of multiple investigator-initiated expanded access or state access programs for a compassionate prospective interventional study: CDKL5 deficiency disorder (n = 20), Aicardi syndrome (n = 19), Dup15q syndrome (n = 8), and Doose syndrome (n = 8). These patients were treated at 11 institutions from January 2014 to December 2016. Results: The percent change in median convulsive seizure frequency for all patients taking CBD in the efficacy group decreased from baseline [n = 46] to week 12 (51.4% [n = 35], interquartile range (IQR): 9–85%) and week 48 (59.1% [n = 27], IQR: 14–86%). There was a significant difference between the percent changes in monthly convulsive seizure frequency during baseline and week 12, χ 2 (2) = 22.9, p = 0.00001, with no difference in seizure percent change between weeks 12 and 48. Of the 55 patients in the safety group, 15 (27%) withdrew from extended observation by week 144: 4 due to adverse effects, 9 due to lack of efficacy, 1 withdrew consent, and 1 was lost to follow-up. Significance: This open-label drug trial provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies. This study extended analysis of the prior report from 12 weeks to 48 weeks of efficacy data and suggested that placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in these epileptic encephalopathies.
AB - Objective: We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. Methods: We included patients aged 1–30 years with severe childhood-onset epilepsy who received CBD for ≥10 weeks as part of multiple investigator-initiated expanded access or state access programs for a compassionate prospective interventional study: CDKL5 deficiency disorder (n = 20), Aicardi syndrome (n = 19), Dup15q syndrome (n = 8), and Doose syndrome (n = 8). These patients were treated at 11 institutions from January 2014 to December 2016. Results: The percent change in median convulsive seizure frequency for all patients taking CBD in the efficacy group decreased from baseline [n = 46] to week 12 (51.4% [n = 35], interquartile range (IQR): 9–85%) and week 48 (59.1% [n = 27], IQR: 14–86%). There was a significant difference between the percent changes in monthly convulsive seizure frequency during baseline and week 12, χ 2 (2) = 22.9, p = 0.00001, with no difference in seizure percent change between weeks 12 and 48. Of the 55 patients in the safety group, 15 (27%) withdrew from extended observation by week 144: 4 due to adverse effects, 9 due to lack of efficacy, 1 withdrew consent, and 1 was lost to follow-up. Significance: This open-label drug trial provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies. This study extended analysis of the prior report from 12 weeks to 48 weeks of efficacy data and suggested that placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in these epileptic encephalopathies.
KW - Aicardi syndrome
KW - CDKL5 deficiency disorder
KW - Cannabidiol
KW - Doose syndrome
KW - Dup15q syndrome
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UR - http://www.scopus.com/inward/citedby.url?scp=85049603152&partnerID=8YFLogxK
U2 - 10.1016/j.yebeh.2018.05.013
DO - 10.1016/j.yebeh.2018.05.013
M3 - Article
C2 - 30006259
AN - SCOPUS:85049603152
SN - 1525-5050
VL - 86
SP - 131
EP - 137
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
ER -