title: Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies.
abstract: This analysis was conducted to assess the tolerability, safety, and efficacy of brivaracetam (BRV) for adjunctive treatment of focal (partial-onset) seizures in patients aged ≥65 years.
  
  
  
  Safety/tolerability and efficacy data for patients aged ≥65 years were pooled from three randomized, double-blind, placebo-controlled, fixed-dose Phase III studies (NCT00490035, NCT00464269, and NCT01261325). Data were pooled by treatment group: placebo or the proposed therapeutic dose range of 50-200 mg/day: BRV 50, 100, 200mg/day.
  
  
  
  Thirty-two patients aged ≥65 years were randomized to placebo or BRV 50-200 mg/day. Of these, 30 patients (93.8%) completed their respective study. In the safety population (n=32), 87.5% placebo- vs 73.3% BRV-treated patients reported treatment-emergent adverse events (TEAEs) during the treatment period; most commonly, headache (25.0% vs 12.5%), paresthesia (0% vs 12.5%), and somnolence (50.0% vs 12.5%) for placebo- vs BRV-treated patients, respectively. During the treatment period, drug-related TEAEs were reported by 62.5% of placebo- vs 53.3% of BRV-treated patients, and serious TEAEs (SAEs) were reported by 0% of placebo- and 4.2% of BRV-treated patients; there were no drug-related SAEs and no deaths. Three SAEs (placebo 1/8; BRV 2/24) and two deaths (placebo 1/8; BRV 1/24) occurred in the post-treatment period. In the efficacy population (n=31), median percent reduction from baseline in focal seizure frequency/28days was 14.0% for placebo vs 25.5%, 49.6%, and 74.9% for BRV 50, 100, and 200 mg/day, respectively. The ≥50% responder rate was 14.3% for placebo vs 25.0%, 50.0%, and 66.7% for BRV 50, 100, and 200 mg/day, respectively.
  
  
  
  Safety/tolerability and efficacy findings in this small subgroup of older patients treated with adjunctive BRV are consistent with those observed in the much larger overall pooled population. BRV may be a suitable adjunctive treatment for older patients with uncontrolled focal seizures. Further larger studies in this population are warranted.
authors: University of Glasgow, Glasgow, UK. Electronic address: Martin.Brodie@glasgow.ac.uk.
authors: Martin J
authors: MJ
authors: Brodie
authors: UCB Pharma, Raleigh, NC, USA. Electronic address: john.whitesides@ucb.com.
authors: John
authors: J
authors: Whitesides
authors: UCB Pharma, Raleigh, NC, USA. Electronic address: jasd54@gmail.com.
authors: Jimmy
authors: J
authors: Schiemann
authors: UCB Pharma, Smyrna, GA, USA. Electronic address: joseph.dsouza@ucb.com.
authors: Joseph
authors: J
authors: D'Souza
authors: UCB Pharma, Raleigh, NC, USA. Electronic address: martin.johnson@ucb.com.
authors: Martin E
authors: ME
authors: Johnson
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*; D013812:Therapeutics
chemical_list: D000927:Anticonvulsants; D011760:Pyrrolidinones; C482793:brivaracetam
keywords: Brivaracetam; Efficacy; Elderly; Epilepsy; Safety; Tolerability