Cannabidiol in conjunction with clobazam: analysis of four randomized controlled trials.
Gunning et al.·Acta Neurologica ScandinavicaImpact 0.5
Klarer NutzenGRADEHoch47 Zitate
Stichprobek = 4 Studien n = 714 Pat.
Dauer14 Wochen
KontrollePlacebo
EndpunktAnfallsfrequenz
Verblindungdoppelblind
DesignMeta-Analyse (4 Phase-3-RCTs)
Cannabinoidcbd
Applikationoral
”Kernaussage
CBD reduzierte die primäre Anfallsfrequenz signifikant vs. Placebo bei LGS und Dravet-Syndrom, sowohl in der Gesamtpopulation als auch bei Patienten unter Clobazam; sekundäre Endpunkte bestätigten die Anfallskontrolle.
Zusammenfassung
Meta-Analyse über 4 Phase-3-RCTs (k=4, n=714; LGS n=396, DS n=318); add-on CBD 10/20 mg/kg/Tag vs. Placebo. Primäranfall-Frequenz reduziert: LGS Treatment Ratio 0,70 [95% CI 0,62–0,80], DS 0,71 [95% CI 0,60–0,83]; unter Komedikation Clobazam noch stärker (LGS 0,56 [95% CI 0,47–0,67], DS 0,63 [95% CI 0,52–0,77]). Häufigere Somnolenz/Sedierung in CBD+Clobazam-Gruppe.
P
PopulationKinder und Erwachsene mit Lennox-Gastaut-Syndrom (n=396) und Dravet-Syndrom (n=318), gepoolte Auswertung von vier Phase-3-RCTs, Teilgruppe: Patienten unter Komedikation mit Clobazam
I
InterventionPflanzlich gewonnenes, hochgereinigtes Cannabidiol (Epidiolex/Epidyolex, 100 mg/ml oral) 10 oder 20 mg/kg/Tag als Add-on
C
KontrollePlacebo
O
OutcomeReduktion der primären Anfallsfrequenz: LGS gesamt Treatment Ratio 0,70 (95%-KI 0,62–0,80); DS gesamt 0,71 (95%-KI 0,60–0,83); unter Clobazam: LGS 0,56 (95%-KI 0,47–0,67), DS 0,63 (95%-KI 0,52–0,77)
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Hoch
Höchste von vier GRADE-Stufen, die Effektschätzung ist sehr verlässlich.
Qualitätsprofil
Größe★★★★★
VerblindungDoppelblind
EffektstärkeKlarer Nutzen
Zitate / Jahr★★★★★
Autoren
Gunning B, Mazurkiewicz-Beldzinska M, Chin RFM, Bhathal H, Nortvedt C, Dunayevich E, Checketts D
To assess the efficacy and safety profile of add-on cannabidiol (CBD) in patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) on clobazam and in the overall population of four randomized, controlled phase 3 trials. Patients received plant-derived, highly purified CBD medicine (Epidiolex in the USA; Epidyolex in Europe; 100 mg/ml oral solution) at a dose of 10 or 20 mg/kg/day, or placebo for 14 weeks. A subgroup analysis of patients on clobazam and meta-analysis by syndrome were conducted. The primary endpoint was percentage reduction in primary seizure type during the treatment period. 396 patients with LGS (49% on clobazam) and 318 patients with DS (64% on clobazam) were included. CBD treatment resulted in a reduction in primary seizure frequency vs placebo in the overall population (treatment ratio [95% confidence interval]: LGS, 0.70 [0.62-0.80]; DS, 0.71 [0.60-0.83]) and in patients receiving clobazam (LGS, 0.56 [0.47-0.67]; DS, 0.63 [0.52-0.77]). The antiseizure efficacy of CBD was also demonstrated across other endpoints vs placebo (≥50% responder rate, total seizure frequency, number of seizure-free days, and Subject/Caregiver Global Impression of Change scores) in the overall populations and in patients receiving clobazam. There were higher incidences of somnolence and sedation in patients on CBD and clobazam. Most incidences of elevated transaminases occurred in patients on concomitant valproate and, to a lesser extent, clobazam. Add-on CBD was effective in reducing seizures in the overall populations and in conjunction with clobazam. Somnolence and sedation occurred more frequently in patients on CBD and clobazam.