Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 131-137 |
| Number of pages | 7 |
| Journal | Epilepsy and Behavior |
| Volume | 86 |
| DOIs | |
| State | Published - Sep 1 2018 |
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Keywords
- Aicardi syndrome
- CDKL5 deficiency disorder
- Cannabidiol
- Doose syndrome
- Dup15q syndrome
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Behavioral Neuroscience
Cite this
Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. / Devinsky, Orrin; Verducci, Chloe; Thiele, Elizabeth A.; Laux, Linda C.; Patel, Anup D.; Filloux, Francis; Szaflarski, Jerzy P.; Wilfong, Angus; Clark, Gary D.; Park, Yong D; Seltzer, Laurie E.; Bebin, E. Martina; Flamini, Robert; Wechsler, Robert T.; Friedman, Daniel.
In: Epilepsy and Behavior, Vol. 86, 01.09.2018, p. 131-137.Research output: Contribution to journal › Article
}
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
PY - 2018/9/1
Y1 - 2018/9/1
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
UR - http://www.scopus.com/inward/record.url?scp=85049603152&partnerID=8YFLogxK
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
VL - 86
SP - 131
EP - 137
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
SN - 1525-5050
ER -