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
Klarer NutzenGRADENiedrig188 Zitate
Stichproben = 55 Pat.
Dauerbis zu 144 Wochen
EndpunktAnfallsfrequenz
Verblindungn.a.
DesignOpen-label Expanded Access Studie (multi-center, Klasse-III-Evidenz)
Cannabinoidcbd
Applikationoral
”Kernaussage
Adjuvantes CBD reduzierte die konvulsive Anfallsfrequenz signifikant und anhaltend über 48 Wochen gegenüber Baseline.
Zusammenfassung
n=46 (Effizienzgruppe; n=55 Sicherheitsgruppe), seltene Epilepsie-Syndrome (CDKL5, Aicardi, Dup15q, Doose), CBD (Epidiolex) als Add-on, multi-center. Mediane konvulsive Anfallsfrequenz reduziert um 51,4% nach 12 Wochen und 59,1% nach 48 Wochen (χ²(2)=22,9, p=0,00001). 27% Abbruchrate bis Woche 144.
P
PopulationKinder und Erwachsene (1–30 Jahre) mit behandlungsresistenter Epilepsie bei CDKL5-Defizienz-Störung, Aicardi-Syndrom, Dup15q-Syndrom und Doose-Syndrom; Sicherheitsgruppe n=55, Effizienzgruppe n=46
OutcomeMediane Reduktion der konvulsiven Anfallsfrequenz um 51,4 % bis Woche 12 und 59,1 % bis Woche 48 gegenüber Baseline (p=0,00001); kein signifikanter Unterschied zwischen Woche 12 und 48
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Niedrig
Zweite von vier GRADE-Stufen, die Effektschätzung ist begrenzt verlässlich.
Herabgestuft wegen
VerzerrungsrisikoUngenauigkeit
Qualitätsprofil
Größe★★★★★
Verblindung—
EffektstärkeKlarer Nutzen
Zitate / Jahr★★★★★
Autoren
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.