title: Efficacy and tolerability of brivaracetam compared to lacosamide, eslicarbazepine acetate, and perampanel as adjunctive treatments in uncontrolled focal epilepsy: Results of an indirect comparison meta-analysis of RCTs.
abstract: BACKGROUND
  Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) have been recently marketed as adjunctive treatments for focal onset seizures. To date, no randomized controlled trial (RCT) has directly compared BRV with ESL, LCM, or PER.
  
  
  OBJECTIVE
  To compare BRV with the other add-on AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and tolerability through an adjusted, common-reference based indirect comparison meta-analysis.
  
  
  METHODS
  We systematically searched RCTs in which add-on treatment with ESL or LCM in patients with focal onset seizures have been compared with placebo. Efficacy and tolerability outcomes were considered. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of BRV, LCM, ESL, or PER versus placebo. Adjusted indirect comparisons were then made between BRV and the other three AEDs using the obtained results, comparing the minimum and the highest effective recommended daily dose of each drug.
  
  
  RESULTS
  Seventeen RCTs, with a total of 4971 patients were included. After adjusting for dose-effects, indirect comparisons showed no difference between BRV and LCM, ESL, or PER for responder rate and seizure freedom. Lower adverse events were observed with high dose BRV compared to high dose ESL or PER, but no difference was found in withdrawing because of adverse events.
  
  
  CONCLUSIONS
  Indirect comparisons do not demonstrate a significant difference in efficacy between add-on BRV and LCM, ESL, or PER in focal epilepsy, and might suggest a better tolerability of BRV than ESL, and possibly also PER, at the highest effective recommended dose.
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Italy; Division of Neurology, Franz Tappeiner Hospital, Merano, Italy. Electronic address: dr.francescobrigo@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brigo
authors.affiliation: School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy.
authors.forename: Nicola Luigi
authors.initials: NL
authors.lastname: Bragazzi
authors.affiliation: Division of Neurology, Franz Tappeiner Hospital, Merano, Italy; Department of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Nardone
authors.affiliation: Department of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University, Salzburg, Austria; Center for Cognitive Neuroscience, Salzburg, Austria; University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D003984:Dibenzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D000078334:Lacosamide; D009570:Nitriles; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D003984:Dibenzazepines; D009570:Nitriles; D011728:Pyridones; D011760:Pyrrolidinones; D000078334:Lacosamide; C416835:eslicarbazepine acetate; C551441:perampanel; C482793:brivaracetam
keywords: Brivaracetam; Eslicarbazepine acetate; Focal epilepsy; Lacosamide; Meta-analysis; Perampanel