Study register · detailOpen-label Expanded Access Studie (multi-center, Klasse-III-Evidenz) · Epilepsy · 2018
Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes.
Devinsky et al.·Epilepsy & BehaviorImpact 2.4
Clear benefitGRADELow188 citations
Samplen = 55 Pat.
Durationup to 144 weeks
EndpointSeizure frequency
Blindingn.a.
DesignOpen-label Expanded Access Studie (multi-center, Klasse-III-Evidenz)
Cannabinoidcbd
Routeoral
”Key finding
Adjuvant CBD significantly and durably reduced convulsive seizure frequency over 48 weeks versus baseline.
Summary
n=46 (efficacy group; n=55 safety group), rare epilepsy syndromes (CDKL5, Aicardi, Dup15q, Doose), CBD (Epidiolex) as add-on, multi-center. Median convulsive seizure frequency reduced by 51,4% after 12 weeks and 59,1% after 48 weeks (χ²(2)=22,9, p=0,00001). 27% discontinuation rate by week 144.
P
PopulationChildren and adults (1–30 years) with treatment-resistant epilepsy in CDKL5 deficiency disorder, Aicardi syndrome, Dup15q syndrome and Doose syndrome; safety group n=55, efficacy group n=46
OutcomeMedian reduction in convulsive seizure frequency of 51,4 % by week 12 and 59,1 % by week 48 versus baseline (p=0,00001); no significant difference between week 12 and 48
Confidence in the evidence
Very lowLowModerateHigh
Low
The second of four GRADE levels, the effect estimate is of limited reliability.
Downgraded for
Risk of biasImprecision
Quality profile
Sample size★★★★★
Blinding—
Effect sizeClear benefit
Citations / year★★★★★
Authors
Devinsky O, Verducci C, Thiele EA, Laux LC, Patel AD, Filloux F, Szaflarski JP, Wilfong A, Clark GD, Park YD, Seltzer LE, Bebin EM, Flamini R, Wechsler RT, Friedman D.
Design: Open-label Expanded Access Studie (multi-center, Klasse-III-Evidenz)
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Abstract
<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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<sup>2</sup>(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.<h4>Significance</h4>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.