Efficacy and safety of six new antiseizure medications for adjunctive treatment of focal epilepsy and epileptic syndrome: A systematic review and network meta-analysis.
Six new antiepileptic drugs show varying efficacy depending on epilepsy type: brivaracetam effective in focal epilepsy (RR=2,18), cenobamate most effective in focal epilepsy at higher dose but with more side effects, cannabidiol effective in Lennox-Gastaut and Dravet syndrome, fenfluramine best for Dravet syndrome with few side effects, everolimus effective in tuberous sclerosis.
Summary
Network meta-analysis (NMA) across k=20 RCTs (n=5.516) on 6 new antiepileptic drugs (including cannabidiol/CBD) in focal epilepsy, Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS) and TSC. CBD showed the highest ranking probability in LGS (SUCRA 88,4 %), SUCRA 66,2 % in DS, but was not better than placebo in adult focal epilepsy (RR=0,83, 95%-CI: 0,36–1,93). Best overall strategy for focal epilepsy: cenobamate 300 mg (SUCRA 91,8 %).
P
PopulationAdults with focal epilepsy as well as adolescents with Dravet syndrome, Lennox-Gastaut syndrome or tuberous sclerosis, pooled n=5516
I
InterventionSix new antiepileptic drugs as add-on therapy: brivaracetam, cenobamate, cannabidiol, fenfluramine, everolimus, soticlestat
C
ControlPlacebo (and indirect comparisons between the agents via network meta-analysis)
O
Outcome50% responder rate and discontinuation rate/SAEs: cenobamate 300 mg most effective for focal epilepsy (SUCRA 91,8%); fenfluramine best benefit-risk balance in Dravet syndrome (SUCRA 91,2% efficacy, 12,5% SAEs); cannabidiol effective in LGS (SUCRA 88,4%) and DS (SUCRA 66,2%), but not better than placebo in focal epilepsy (RR=0,83; 95% CI: 0,36–1,93); everolimus more effective than cannabidiol in TSC (SUCRA 89,7%)
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Quality profile
Sample size★★★★★
Blinding—
Effect sizeClear benefit
Citations / year★★★★★
Authors
Tong J, Ji T, Liu T, Liu J, Chen Y, Li Z, Lu N, Li Q
This study aimed to evaluate the efficacy and safety of six new antiseizure medications (ASMs) for adjunctive treatment in adult patients with focal epilepsy and adolescents with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex (TSC). A comprehensive literature search was performed using PubMed, Medline, Embase, and Cochrane library databases from inception to October 13, 2023. We included published studies for a systematic review and a network meta-analysis (NMA). The efficacy and safety were reported in terms of a 50% response rate and dropout rate along with serious adverse events (SAEs). The outcomes were ranked with the surface under the cumulative ranking curve (SUCRA). Twenty eligible trials with 5516 patients and 21 interventions, including placebo, contributed to the analysis. Included ASMs were brivaracetam (BRV), cenobamate (CBM), cannabidiol (CBD), fenfluramine (FFM), everolimus (ELM), and soticlestat (SLT). The six new ASMs were compared in four different epilepsy subtypes. In focal epilepsy treatment, BRV seemed to be safe [vs placebo, risk ratio (RR) = 0.69, 95% confidence interval (CI): 0.25-1.91] and effective (vs placebo, RR = 2.18, 95% CI: 1.25-3.81). In treating focal epilepsy, CBM 300 mg was more effective at a 50% response rate (SUCRA 91.8%) compared with BRV and CBD. However, with the increase in dosage, more SAEs (SUCRA 85.6%) appeared compared with other ASMs. CBD had good efficacy on LGS (SUCRA 88.4) and DS (SUCRA 66.2), but the effect on adult focal epilepsy was not better than that of placebo [vs placebo, RR = 0.83 (0.36-1.93)]. The NMA indicated that the likelihood of the most appropriate intervention (SUCRA 91.2%) with minimum side effects (SUCRA 12.5%) for the DS was FFM. Compared with CBD, high exposure to ELM demonstrated a more effective treatment of TSC (SUCRA 89.7%). More high-quality SLT studies are needed to further evaluate the efficacy and safety.