title: Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study.
abstract: BACKGROUND
  Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients.
  
  
  METHODS
  This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged ≥ 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age.
  
  
  RESULTS
  Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs.
  0.46 (0.16-1.33); LEV vs.
  0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively.
  
  
  CONCLUSIONS
  Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged ≥ 60 years with newly diagnosed epilepsy.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00175903 ; September 9, 2005.
authors.affiliation: Epilepsy Program, Division of Neurology, Queen Elizabeth II Health Science Center, Dalhousie University, Halifax, Canada. B.Pohlmann-Eden@dal.ca.|Brain Repair Center, Dalhousie University, Halifax, Canada. B.Pohlmann-Eden@dal.ca.
authors.forename: Bernd
authors.initials: B
authors.lastname: Pohlmann-Eden
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Marson
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Noack-Rink
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ramirez
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Azita
authors.initials: A
authors.lastname: Tofighy
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Konrad J
authors.initials: KJ
authors.lastname: Werhahn
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Imane
authors.initials: I
authors.lastname: Wild
authors.affiliation: Department of Neurology, Paracelsus Medical University, Christian Doppler Klinik, and Centre for Cognitive Neuroscience, Salzburg, Austria.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use; D002220:Carbamazepine / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D000077287:Levetiracetam; D014635:Valproic Acid; D010889:Piracetam
keywords: Antiepileptic drug; Elderly; Epilepsy; Levetiracetam; Monotherapy