Langsame CBD-Titration reduzierte die Anfallsfrequenz klinisch relevant bei akzeptablem Sicherheitsprofil, jedoch mit unerwünschten Ereignissen bei knapp der Hälfte der Patienten.
Zusammenfassung
Prospektive offene multizentrische Studie (n=125, 62 LGS, 48 Dravet-Syndrom) mit langsamem CBD-Titrations-Protokoll (Zieldosis 10 mg/kg/Tag, max. 20 mg/kg/Tag); Anfallsfrequenz nach 6 Monaten -41% ± 37,5% gegenüber Baseline, 37,8% (28/74) der Patienten erreichten ≥50% Anfallsreduktion; UAW bei 48,8% (61/125), häufigste: Somnolenz, Asthenie, Verhaltensstörungen; langsamere Titration verbesserte Verträglichkeit bei vergleichbarer Wirksamkeit zu früheren Studien.
P
PopulationPädiatrische Patienten mit pharmakoresistenter Epilepsie (Dravet-Syndrom, Lennox-Gastaut-Syndrom u. a.), n=125, multizentrisch (7 französische Zentren)
OutcomeAnfallsfrequenzreduktion ab Baseline bei M6: -41% ± 37,5%; 37,8% der Patienten erreichten ≥50%-Reduktion; unerwünschte Ereignisse bei 48,8%, signifikant höher bei M2 (p=0,03) und mit steigender AED-Anzahl (p=0,03)
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Moderat
Dritte von vier GRADE-Stufen, die Effektschätzung ist wahrscheinlich verlässlich.
Herabgestuft wegen
Verzerrungsrisiko
Qualitätsprofil
Größe★★★★★
VerblindungOffen
EffektstärkeGemischt
Zitate / Jahr★★★★★
Autoren
D'Onofrio G, Kuchenbuch M, Hachon-Le Camus C, Desnous B, Staath V, Napuri S, Ville D, Pedespan JM, Lépine A, Cances C, de Saint-Martin A, Teng T, Chemaly N, Milh M, Villeneuve N, Nabbout R.
<b>Objective:</b> To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. <b>Methods:</b> We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at least 1 month and then gradually increased to a maximum dose of 20 mg/kg/day. We analyzed AEs and efficacy at M1 (month 1), M2, and M6, comparing two sets of subgroups: Dravet syndrome (DS) vs. Lennox-Gastaut (LGS) and patients with clobazam (CLB+) vs. patients without (CLB-). <b>Results:</b> One hundred and twenty-five patients were enrolled (62 LGS, 48 DS, 5 Tuberous sclerosis, and 10 other etiologies). Median concomitant antiepileptic drugs (AEDs) was three (25th percentile: 3, 75th percentile: 4). Patients received a dose of 10 (10-12), 14 (10-20), and 15.5 mg/kg/day (10-20) at M1, M2, and M6, respectively. Twenty-six patients discontinued CBD, 19 due to lack of efficacy, 2 due to AEs, 4 for both, and 1 had a sudden unexpected death in epilepsy. AEs were reported in 61 patients (48.8%), mainly somnolence (<i>n</i> = 26), asthenia (<i>n</i> = 20), and behavior disorders (<i>n</i> = 16). Abnormal transaminases (≥3 times) were reported in 11 patients receiving both valproate and clobazam. AEs were significantly higher at M2 (<i>p</i> = 0.03) and increased with the number of AEDs (<i>p</i> = 0.03). At M6, total seizure frequency change from baseline was -41% ± 37.5% (mean ± standard deviation), and 28 patients (37.8%) had a reduction ≥50%. AE and efficacy did not differ between DS vs. LGS and CLB+ vs. CLB- patients. <b>Significance:</b> A slower titration of CBD dose delivered better tolerance with comparable efficacy to previous trials. Concomitant CLB did not increase efficacy rates but in a few cases increased AEs. This slow titration scheme should help guide clinicians prescribing CBD and allow patients to benefit from its potential efficacy.