Network meta-analysis of antiepileptic drugs in focal drug-resistant epilepsy

Abstract

ObjectiveTo compare and rank the efficacy and acceptability of new antiepileptic drugs (AEDs) for patients with focal drug-resistant epilepsy. MethodsPubMed, EMBASE, Cochrane databases and Clinicaltrials.gov were systematically searched from their inception through January 1, 2020, to identify trials evaluating AEDs for focal drug-resistant epilepsy. We included randomized controlled clinical trials (RCTs) comparing new AEDs with placebo or with other AEDs as adjunctive therapy for focal drug-resistant epilepsy. A Bayesian network meta-analysis was performed to determine efficacy and acceptability, as reflected by odds ratios (ORs), 95 % credible intervals (CrIs) with random-effects and consistent models. ResultsSixty-two RCTs were included, involving 12,739 patients with focal drug-resistant epilepsy. Regarding the seizure-free rate (40 RCTs involving 9,136 patients), 8 AEDs were more efficacious than placebo, with lnORs ranging between 1.69 for brivaracetam (95 % CrI, 0.56–2.81) and 0.72 for pregabalin (95 % CrI, 0.12–1.32). Regarding the responder rate, all AEDs except oxcarbazepine were more efficacious than placebo, with lnORs ranging between 1.31 for levetiracetam (95 % CrI, 0.92–1.71) and 0.66 for carisbamate (95 % CrI, 0.17–1.14). Regarding acceptability (60 RCTs comprising 12,139 patients), 9 AEDs were inferior to placebo. Estimated from seizure-free rate, brivaracetam was ranked as the most efficacious AED based on cumulative probability plots and SUCRAs, with fatigue as the main adverse event. ConclusionThe results indicate that, based on seizure-free rate and all-cause discontinuation rate, brivaracetam is the most efficacious and acceptable AED, with mild adverse events and acknowledgement of potential publication bias.