Study register · detailNetzwerk-Meta-Analyse · Epilepsy · 2022
Short-term and long-term efficacy and safety of antiseizure medications in Lennox Gastaut syndrome: A network meta-analysis.
Devi et al.·SeizureImpact 2.2
Clear benefitGRADEModerate24 citations
Samplek = 15 Studien n = 1.263 Pat.
DurationShort- and long-term results
ControlPlacebo or other ASMs
EndpointSeizure reduction ≥50%
Blindingn.a.
DesignNetzwerk-Meta-Analyse
Cannabinoidcbd
”Key finding
High-dose clobazam (CLB_H) showed the best efficacy for ≥50% reduction of drop seizures (OR: 4,9) with the highest ranking (SUCRA 0,89), while high-dose CBD showed higher rates of adverse events; long-term data confirmed CLB_H as the most effective and safest option.
Summary
Network meta-analysis (k=15 RCTs/OLE, n=1.263, age 2–54 years) on 6 antiepileptics including CBD in Lennox-Gastaut syndrome. High-dose CBD (20 mg/kg/day) significantly reduced drop seizures (OR=3,8; 95%-CI 1,6–9,0 vs. placebo); high-dose clobazam led the efficacy ranking (OR=4,9; SUCRA=0,89). Long-term CBD therapy was associated with a higher TEAE rate (96%; 95%-CI 95–98%). CLB, CBD and rufinamide are regarded as the most effective and safest option.
P
PopulationChildren and adults with Lennox-Gastaut syndrome (LGS), age 2–54 years, n=1263 from 15 studies
OutcomeCLB_H (1,0 mg/kg/day) showed the highest probability of a ≥50% reduction in drop-seizure frequency (OR 4,9; 95%-CI 2,3–10,8; SUCRA 0,89); CBD_H (20 mg/kg/day) had the highest probability of TEAEs (OR 3,8; 95%-CI 1,6–9,0; SUCRA 0,85). Long-term: CLB 78% responders (95%-CI 70–85%), CBD 96% TEAE rate (95%-CI 95–98%).
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
To assess the short-term and long-term comparative efficacy and safety of ASMs for Lennox-Gastaut syndrome (LGS). Following a systematic literature search, randomized controlled trial (RCT) and open-label extension (OLE) studies on LGS comparing ASMs with placebo or other ASMs were included. ≥50% reduction in drop seizure frequency from baseline and occurrence of treatment-emergent adverse events (TEAEs) were the primary efficacy and safety outcomes. For short-term outcomes, a network meta-analysis (NMA) reporting odds ratio (OR) with 95% confidence intervals (CIs) and hierarchy of competing interventions [surface under the cumulative ranking curve(SUCRA)] was done. Long-term outcomes were reported as proportion with 95% CIs using the random-effects model. Fifteen studies including 1263 participants with LGS (aged 2-54years) receiving any of six ASMs [cannabidiol (CBD), clobazam (CLB), felbamate (FLB), lamotrigine (LTG), rufinamide (RFM), topiramate (TPM)] or placebo were included. High-dose CLB (1.0 mg/kg/day; CLB_H) [OR: 4.9; 95% CI: 2.3-10.8] was significantly associated with ≥50% reduction in drop seizure frequency as compared with placebo, and achieved the highest-ranking probability (0.89) based on SUCRA values (although there was an overlap between confidence intervals of effect sizes of CLB, RFM and CBD), while high-dose CBD (20 mg/kg/day; CBD_H) [OR: 3.8; 95% CI:1.6-9.0] had significantly higher odds for occurrence of any TEAEs and had the highest-ranking probability (0.85). Furthermore, the long-term treatment with CLB [78%; 95% CI: 70-85%] was associated with a significantly higher proportion of patients with reduction in drop-seizures, and long-term use of CBD [96%; 95% CI: 95-98%] was associated with a higher frequency of TEAEs. The study findings suggest that CLB_H, CBD and RFM are the most efficacious and safest in terms of both short and long-term outcomes with CLB_H probably leading the hierarchy. Future head-to-head trials comparing these ASMs are needed.