May 23, 2018

Study: Efficacy of Antiepileptic Drugs in the Adjunctive Treatment of Refractory Partial-Onset Seizures – Meta-Analysis of Pivotal Trials

OBJECTIVE: In 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).

METHODS: A systematic literature review was conducted to identify pivotal AED trials serving as the basis for US Food and Drug Administration (FDA) approval.

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).

RESULTS: A 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.

CONCLUSION: In 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.

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