Brivaracetam add-on for refractory focal epilepsy: A systematic review and meta-analysis

Neurology. 2016 Apr 5;86(14):1344-1352. doi: 10.1212/WNL.0000000000002545. Epub 2016 Mar 4.

Abstract

Objective: To evaluate the efficacy and safety of the new antiepileptic drug brivaracetam (BRV) as add-on treatment for drug-resistant partial epilepsy using meta-analytical techniques.

Methods: Randomized, placebo-controlled, single- or double-blind, add-on trials of BRV in adult patients with drug-resistant partial epilepsy were identified through a systematic literature search. The following outcomes were assessed: 50% or greater reduction in seizure frequency, seizure freedom, incidence of treatment-emergent adverse events (TEAEs), and treatment withdrawal. Risk ratio (RR) with 95% confidence interval was estimated for each outcome.

Results: Six trials were included involving 2,399 participants according to the intent-to-treat, 1,715 for BRV, and 684 for placebo groups, respectively. The pooled RRs for the 50% responders and seizure freedom were 1.79 (1.51-2.12) and 4.74 (2.00-11.25), respectively. The subanalysis by levetiracetam (LEV) status did not show a statistically significant difference in the 50% responder rate when comparing BRV with placebo in patients with concomitant assumption of LEV. The TEAEs significantly associated with BRV were irritability (2.99 [1.28-6.97]), fatigue (2.19 [1.44-3.33]), somnolence (1.97 [1.45-2.68]), and dizziness (1.66 [1.19-2.31]). The overall RRs for treatment withdrawal due to TEAEs or any reason were 1.58 (1.04-2.40) and 1.27 (0.93-1.73), respectively.

Conclusions: In adults with drug-refractory focal epilepsy, add-on BRV was effective to reduce seizure frequency and fairly well-tolerated. Further studies are needed to draw definitive conclusions about its efficacy in non-LEV-naive participants and evaluate its long-term safety profile.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Drug Resistant Epilepsy / drug therapy*
  • Epilepsies, Partial / drug therapy*
  • Humans
  • Outcome Assessment, Health Care / statistics & numerical data*
  • Pyrrolidinones / administration & dosage
  • Pyrrolidinones / pharmacology*
  • Randomized Controlled Trials as Topic / statistics & numerical data*

Substances

  • Anticonvulsants
  • Pyrrolidinones
  • brivaracetam