Study register · detailopen-label extension · Epilepsy · 2021
Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial.
Patel et al.·EpilepsiaImpact 4.1
Clear benefitGRADEModerate107 citations
Samplen = 366 Pat.
DurationMedian 1090 days
EndpointSeizure frequency
Blindingn.a.
Designopen-label extension
Cannabinoidcbd
Routeoral
”Key finding
Sustained reduction in drop seizures of 48–71% and in all seizures of 48–68% over up to 156 weeks; 87% or more of patients/caregivers reported improvement in overall condition.
Summary
n=366 patients with Lennox-Gastaut syndrome (LGS) in an open-label long-term extension (up to 156 weeks); add-on CBD (Epidiolex, 20–30 mg/kg/day) reduced drop seizures by a median of 48–71 % and total seizures by 48–68 % versus baseline; ≥87 % of patients/caregivers reported improvement in global assessment (CGIC); treatment discontinuations due to adverse events 12 %.
P
PopulationPatients with Lennox-Gastaut syndrome (LGS) who had completed previous RCTs, n=366
OutcomeMedian reduction in drop seizures from baseline 48–71 %, total seizures 48–68 % over 156 weeks; ≥87 % of patients/caregivers reported improvement on the CGIC scale; AEs in 96 %, serious AEs in 42 %, discontinuations due to AEs in 12 %
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Risk of bias
Quality profile
Sample size★★★★★
Blinding—
Effect sizeClear benefit
Citations / year★★★★★
Authors
Patel AD, Mazurkiewicz-Bełdzińska M, Chin RF, Gil-Nagel A, Gunning B, Halford JJ, Mitchell W, Scott Perry M, Thiele EA, Weinstock A, Dunayevich E, Checketts D, Devinsky O
Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy that is often treatment resistant. Efficacy and safety of add-on cannabidiol (CBD) to treat seizures associated with LGS was demonstrated in two randomized controlled trials (RCTs). Patients who completed the RCTs were invited to enroll in this long-term open-label extension (OLE) trial, GWPCARE5 (NCT02224573). We present the final analysis of safety and efficacy outcomes from GWPCARE5. Patients received plant-derived highly purified CBD (Epidiolex in the United States; Epidyolex in the European Union; 100 mg/ml oral solution), titrated to a target maintenance dose of 20 mg/kg/day over 2 weeks. Based on response and tolerability, CBD could then be reduced or increased up to 30 mg/kg/day. Of 368 patients with LGS who completed the RCTs, 366 (99.5%) enrolled in this OLE. Median and mean treatment duration were 1090 and 826 days (range = 3-1421), respectively, with a mean modal dose of 24 mg/kg/day. Adverse events (AEs) occurred in 96% of patients, serious AEs in 42%, and AE-related discontinuations in 12%. Common AEs were convulsion (39%), diarrhea (38%), pyrexia (34%), and somnolence (29%). Fifty-five (15%) patients experienced liver transaminase elevations more than three times the upper limit of normal; 40 (73%) were taking concomitant valproic acid. Median percent reductions from baseline ranged 48%-71% for drop seizures and 48%-68% for total seizures through 156 weeks. Across all 12-week visit windows, 87% or more of patients/caregivers reported improvement in the patient's overall condition on the Subject/Caregiver Global Impression of Change scale. Long-term add-on CBD treatment had a similar safety profile as in the original RCTs. Sustained reductions in drop and total seizure frequency were observed for up to 156 weeks, demonstrating long-term benefits of CBD treatment for patients with LGS.