All antiseizure medications showed significantly higher response rates than placebo; rufinamide, cannabidiol and topiramate had the highest probability of at least a 50% reduction in drop seizures, but did not differ significantly from one another. However, cannabidiol, topiramate and rufinamide led to discontinuations more frequently, with cannabidiol significantly higher than placebo, clobazam and lamotrigine.
Summary
NMA of k=8 RCTs (n=1.171) in Lennox-Gastaut syndrome (LGS); compared anticonvulsants: lamotrigine, rufinamide, cannabidiol, topiramate, clobazam, felbamate. SUCRA ranking: rufinamide and cannabidiol with highest probability for ≥50% seizure frequency reduction in drop seizures; no significant difference between treatments among each other. Cannabidiol vs. placebo, clobazam and lamotrigine: significantly higher discontinuation rate (p<0.05).
P
PopulationPatients with Lennox-Gastaut syndrome (LGS), pooled n=1171
ControlPlacebo or active comparators (network meta-analysis)
O
OutcomeRufinamide and cannabidiol with highest probability for ≥50% reduction in drop seizures (SUCRA); cannabidiol with significantly higher discontinuation rate vs. placebo, clobazam and lamotrigine; all ASMs significantly better than placebo
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
To compare and rank the efficacy and safety of antiseizure medication (ASM) in patients with Lennox-Gastaut syndrome (LGS). We included randomized controlled trials (RCTs) assessing the efficacy of ASM for LGS compared with placebo or with each other. The efficacy and safety were reported in terms of an at least 50% monthly seizure frequency reduction in drop seizures, dropout, and serious adverse events. Outcomes were ranked according to the surface under the cumulative ranking curve (SUCRA). A total of eight RCTs with 1171 patients were included, involving six ASMs: lamotrigine, rufinamide, cannabidiol, topiramate, clobazam, and felbamate. The calculated SUCRA showed that rufinamide, cannabidiol, and topiramate had the highest probability of achieving a response; however, no significant differences were found among these treatments. Cannabidiol, topiramate, and rufinamide were more likely to result in dropouts; moreover, a significantly greater percentage of patients receiving cannabidiol experienced premature discontinuation as compared to placebo, clobazam, and lamotrigine. All ASMs showed a significantly higher response rate than placebo. SUCRA ranking demonstrated that rufinamide and cannabidiol are more efficacious than other treatments in reducing drop seizures. However, there was no significant difference between these treatments.