Efficacy of antiepileptic drugs in the adjunctive treatment of refractory partial-onset seizures: Meta-analysis of pivotal trials

Abstract

ObjectiveIn the absence of randomized clinical trials (RCTs) assessing the relative efficacy of antiepileptic drugs (AEDs), meta-analyses are useful resources for informing treatment choices. This meta-analysis assesses the relative efficacy and tolerability of AEDs for adjunctive treatment of refractory partial onset seizures (POS). MethodsA systematic literature review was conducted to identify pivotal AED trials serving as the basis for US Food and Drug Administration (FDA) approval. Inclusion criteria: 1) double-blind, placebo-controlled, parallel-group design, with 8- to 14-week maintenance period; 2) enrolled patients ≥16years with refractory POS, including complex partial seizures; 3) study was conducted between 1993 and 2013; and; 4) patients received FDA-approved dosage. Outcomes analyzed: 1) 50% responder rate (≥50% reduction from baseline in seizure frequency); 2) seizure freedom (proportion of seizure-free patients); and 3) discontinuation due to adverse events (AEs). DerSimonian and Laird random-effects model was used to derive odds ratios (OR) and 95% confidence intervals (CI). ResultsA total of 29 publications for 11 AEDs (eslicarbazepine, ezogabine, gabapentin, lacosamide, levetiracetam, perampanel, pregabalin, tiagabine, topiramate, vigabatrin, and zonisamide) were included in the meta-analysis. Tiagabine 56mg/day (OR 8.82, 95% CI: 2.77–28.11), pregabalin 600mg/day (OR 8.08, 95% CI: 5.45–11.98), and vigabatrin 3000mg/day (OR 6.23, 95% CI: 1.46–26.20) had the highest OR versus placebo of 50% response. The odds of seizure freedom were ≥7 times greater than placebo for levetiracetam 3000mg/day (OR 11.00, 95% CI: 2.08–58.06), vigabatrin 3000mg/day (OR 7.41, 95% CI: 1.31–41.84), and ezogabine 1200mg/day (OR 7.09, 95% CI: 0.36–58.06). Patients were more likely to discontinue any AED (except low-dose pregabalin) than placebo. ConclusionIn this meta-analysis of >9000 patients, those treated with AEDs were more likely than placebo to achieve seizure response or freedom. Patients receiving pregabalin, tiagabine, and vigabatrin had the highest odds of ≥50% reduction in seizures, and patients receiving ezogabine, levetiracetam, and vigabatrin had the highest odds of seizure freedom.