12-Month Effectiveness and Tolerability of Brivaracetam in the Real-World: The International EXPERIENCE Pooled Analysis
Vicente Villanueva1, Wendyl D'Souza2, Edward Faught3, Pavel Klein4, Markus Reuber5, Felix Rosenow6, Javier Salas-Puig7, Victor Soto Insuga8, Adam Strzelczyk6, Jerzy P. Szaflarski9, Herve Besson10, Tony Daniels11, Florin Floricel12, Cedric Laloyaux13, Veronica Sendersky13, Sophia Zhou11, Bernhard J. Steinhoff14
1Hospital Universitario y Politécnico La Fe, Valencia, Spain, 2Department of Medicine, St Vincent’s Hospital Melbourne, The University of Melbourne, Melbourne, Australia, 3Emory Epilepsy Center, Atlanta, GA, USA, 4Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA, 5The University of Sheffield, Sheffield, UK, 6Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Frankfurt, Germany, 7Universitari Vall d’Hebron, Barcelona, Spain, 8Pediatric Neurology, Pediatric Neurology, Hospital Universitario Infantil Niño Jesús, Madrid, Spain, 9UAB Epilepsy Center, Birmingham, AL, USA, 10UCB Pharma, Breda, Netherlands, 11UCB Pharma, Morrisville, NC, USA, 12UCB Pharma, Monheim am Rhein, Germany, 13UCB Pharma, Brussels, Belgium, 14Kork Epilepsy Center, Kehl-Kork and Medical Faculty, University of Freiburg, Freiburg, Germany
Objective:
Effectiveness and tolerability of brivaracetam (BRV) in routine practice were assessed in a large international population (United States/Europe/Australia).
Background:
To date, real-world evidence studies of BRV have been restricted in scope, location, and numbers, limiting identification of trends in BRV response and tolerability.
Design/Methods:
EXPERIENCE/EPD332 is a meta-analysis of patient-level data from patients with epilepsy initiating BRV in clinical practice. Effectiveness and tolerability outcomes were assessed at 3/6/12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Subgroup analyses were performed by number of prior antiseizure medications (ASMs).
Results:
Analyses included 1644 adults; 92.2%/7.7% had focal-onset/generalized-onset seizures at baseline (mean: 5.5 prior ASMs at baseline [n=1620], 2.1 concomitant ASMs at index [n=1644]). Median BRV duration: 345.5 days (Q1–Q3, 131.5–410.9; n=1629); median dose at index: 100 mg/day (Q1–Q3, 50.0–100.0; n=1615). ≥50% seizure reduction from baseline at 3/6/12 months: 32.1%/36.7%/36.9% (n=619/867/822); seizure freedom (SF; no seizures within 3 months before timepoint): 22.4%/17.9%/14.9% (n=923/1165/1111); continuous SF after baseline (CSF; no seizures reported for any timepoint after baseline): 22.4%/15.7%/11.7% (n=923/1165/1111). Treatment-emergent adverse events (TEAEs) since prior visit: 25.6%/14.2%/9.3% of patients at 3/6/12 months (n=1542/1376/1232). At 12 months, somnolence was the most common TEAE (2.2%). Of patients with TEAEs at 3/6/12 months, 6.4%/2.6%/2.6% had psychiatric TEAEs and 1.6%/0.8%/0.6% had behavioral TEAEs. During follow-up, 551/1639 (33.6%) patients discontinued BRV. In analyses by number of prior ASMs (n=1620; 0–1/2–3/4–6/≥7 ASMs: 15.4%/21.9%/28.8%/34.0%), ≥50% seizure reduction from baseline generally declined with increasing number of prior ASMs at 3 (48.3%–23.1%), 6 (48.0%–26.5%), and 12 months (45.9%–29.9%), as did SF/CSF. In 0–1/ 2–3/4–6/≥7 ASMs subgroups, TEAE incidences at 12 months were 7.0%/7.4%/11.5%/10.0% (n=214/282/356/359).
Conclusions:
These analyses suggest BRV was effective and well tolerated in highly drug-resistant cohorts. Limitations: challenging to harmonize variables from different studies with mixed populations.