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(Abst. 1.298), 2019

Long-Term Tolerability and Retention of Adjunctive Brivaracetam in Children
Authors: Jan-Peer Elshoff, UCB Pharma, Monheim am Rhein, Germany; Teresa Gasalla, UCB Pharma, Raleigh, NC, USA; Sami Elmoufti, UCB Pharma, Raleigh, NC, USA; Melinda Martin, UCB Pharma, Smyrna, GA, USA; Xavier Nondonfaz, UCB Pharma, Brussels, Belgium; Anup D. Patel, Nationwide Children's Hospital & The Ohio State University College of Medicine, Columbus, OH, USA
Content: Rationale: In the United States, brivaracetam (BRV) is indicated for the treatment of focal seizures in patients 4 years of age and older. This pooled analysis of interim trial data was performed to evaluate long-term tolerability and retention of adjunctive BRV in children younger than 4 years of age with focal seizures. Methods: N01263 (NCT00422422) was an open-label trial of adjunctive BRV in children (aged ≥1 month to <16 years) with epilepsy, uncontrolled by 1–3 concomitant antiepileptic drugs (AEDs). BRV dose was up-titrated over 3 weeks (0.8–4 mg/kg/day). Patients who completed this trial could continue on BRV in an open-label extension trial (N01266, NCT01364597). Patients received BRV at a flexible dose of 1–5 mg/kg/day (maximum 200 mg/day) during long-term evaluation. This pooled interim analysis (cut-off March 15, 2017) was conducted for patients younger than 4 years of age with focal seizures. Kaplan-Meier estimated 12- and 24-month retention rates were calculated from time of first exposure to BRV. Results: 16 patients younger than 4 years of age with focal seizures were enrolled in the initial trial; 14 (87.5%) entered the long-term extension trial. At cut-off, 7 (43.8%) patients were receiving BRV and 9 (56.3%) had discontinued. Most common reasons for discontinuation were lack of efficacy (3 [18.8%]), adverse event (2 [12.5%]), caregiver choice (1 [6.3%]). Mean age was 1.4 years; 12 (75.0%) patients were male (Table 1). Most common modal BRV dose was >3–4 mg/kg/day in 13 (81.3%) patients (≤1 mg/kg/day: 2 [12.5%], >1–2 mg/kg/day: 1 [6.3%]). Total exposure to BRV was 40.8 patient-years; 7 (43.8%) patients had ≥48 months of treatment. Kaplan-Meier estimated 12- and 24-month retention rates were 68.8% (95% confidence interval 40.5–85.6) and 62.5% (34.9–81.1), respectively. All 16 patients had treatment-emergent adverse events (TEAEs), most commonly (≥7 patients) pyrexia, vomiting, nasopharyngitis, and upper respiratory tract infection (Table 2). 10 (62.5%) patients had TEAEs considered drug-related by the investigator, most commonly (≥2 patients) decreased appetite (2 [12.5%]). 8 (50.0%) patients had serious TEAEs; convulsion (2 [12.5%]) was the only serious TEAE in ≥2 patients. 2 (12.5%) patients discontinued due to TEAEs (hepatic enzyme increased [1]; decreased appetite [1]). Conclusions: Long-term adjunctive BRV was generally well tolerated in children under 4 years of age with focal seizures, with few discontinuations due to TEAEs. Kaplan-Meier estimated 1- and 2-year retention was high, suggesting that BRV treatment was effective in this limited number of patients. Funding: UCB Pharma-sponsored
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