title: A common reference-based indirect comparison meta-analysis of eslicarbazepine versus lacosamide as add on treatments for focal epilepsy.
abstract: Eslicarbazepine acetate (ESL) and lacosamide (LCM) have recently emerged as add-on treatments in patients with focal epilepsy experiencing seizures despite adequate monotherapy. Both drugs enhance slow inactivation of voltage-gated sodium channels. To date no randomized controlled trial (RCT) has directly compared ESL with LCM as add-on treatments for focal epilepsy. Our aim was to indirectly compare the efficacy of ESL and LCM used as add-on treatments in patients with focal epilepsy using common reference-based indirect comparison meta-analysis.
  
  
  
  We systematically searched RCTs in which ESL or LCM has been used as add-on treatment in patients with focal epilepsy and compared with placebo. Following outcomes were considered: ≥50% reduction in seizure frequency; seizure freedom; treatment withdrawal for any reason; ≥25% increase in seizure frequency. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of ESL or LCM versus placebo. Adjusted indirect comparisons were then made between ESL and LCM using the obtained results, and comparing the minimum and the highest effective recommended daily dose of each drug.
  
  
  
  Eight studies were included. Indirect comparisons adjusted for dose-effect showed no difference between ESL and LCM for responder rate, seizure freedom, and withdrawal rates. We could not assess increase in seizure frequency due to lack of data.
  
  
  
  Indirect comparisons failed to find a significant difference in efficacy between add-on ESL and LCM in patients with focal epilepsy. Direct head-to-head clinical trials comparing ESL with LCM as add-on antiepileptic treatment are required to confirm these results.
authors.affiliation: Department of Neurosciences, Biomedical, and Movement Sciences, University of Verona, Italy; Department of Neurology, Franz Tappeiner Hospital, Merano, Italy. Electronic address: dr.francescobrigo@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brigo
authors.affiliation: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria; Center for Cognitive Neuroscience, Salzburg, Austria; Department of Public Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T, Austria. Electronic address: e.trinka@salk.at.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
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. Electronic address: robertobragazzi@gmail.com.
authors.forename: Nicola Luigi
authors.initials: NL
authors.lastname: Bragazzi
authors.affiliation: Department of Neurology, Franz Tappeiner Hospital, Merano, Italy; Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria. Electronic address: raffale.nardone@gmail.com.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Nardone
authors.affiliation: Medical Department Eisai s.r.l., San Donato Milanese, Italy. Electronic address: Alberto_Milan@eisai.net.
authors.forename: Alberto
authors.initials: A
authors.lastname: Milan
authors.affiliation: Medical Department Eisai s.r.l., San Donato Milanese, Italy. Electronic address: elisabetta_grillo@eisai.net.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Grillo
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D003984:Dibenzazepines / Q000627:therapeutic use*; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D000078334:Lacosamide
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D003984:Dibenzazepines; D000078334:Lacosamide; C571001:eslicarbazepine
keywords: Efficacy; Eslicarbazepine acetate; Focal epilepsy; Indirect comparison meta-analysis; Lacosamide