Authors :
Cedric Laloyaux, PhD – UCB Pharma; Bernhard Steinhoff, MD, PhD – Kork Epilepsy Center, Kehl-Kork, Germany; Wendyl D'Souza, MBChB – Department of Medicine – St Vincent’s Hospital Melbourne, The University of Melbourne, Melbourne, Australia; Edward Faught, MD – Emory Epilepsy Center, Atlanta, Georgia, US; Pavel Klein, MD – Mid-Atlantic Epilepsy and Sleep Center, Atlanta, Georgia, US; Markus Reuber, MD, PhD – The University of Sheffield, Sheffield, UK; Felix Rosenow, MD – Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Frankfurt, Germany; Javier Salas-Puig, MD – Universitari Vall d’Hebron, Barcelona, Spain; Victor Soto Insuga, MD, PhD – Pediatric Neurology, Hospital Universitario Infantil Niño Jesús, Madrid, Spain; Adam Strzelczyk, MD, MHBA – 9Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Frankfurt, Germany; Jerzy Szaflarski, MD, PhD – UAB Epilepsy Center; Herve Besson, PhD – UCB Pharma, Breda, Netherlands; Tony Daniels, BS – UCB Pharma, Morrisville, North Carolina, US; Florin Floricel, MD, PhD – UCB Pharma, Monheim am Rhein, Germany; Veronica Sendersky, PharmD – UCB Pharma, Brussels, Belgium; Sophia Zhou, MS – UCB Pharma, Morrisville, North Carolina, US; Vicente Villanueva, MD, PhD – Hospital Universitario y Politécnico La Fe, Valencia, Spain
Rationale: This pooled analysis of real-world data from a large international population (North America/Europe/Australia) assessed effectiveness and tolerability of brivaracetam (BRV) in patients with epilepsy by no. of prior antiseizure medications (ASMs) and BRV treatment type.
Methods: Subgroup analysis from EXPERIENCE/EPD332, a pooled analysis of retrospective cohorts that included patients with epilepsy initiating BRV in clinical practice. 50% responder rate (RR; ≥50% seizure reduction from baseline [BL]), seizure freedom (SF; no seizures within 3 months [m] prior to timepoint), continuous SF after BL (CSF; no seizures within 3 m prior to timepoint and previous follow-up timepoints) at 3, 6, 12 m and treatment-emergent adverse events (TEAEs) since prior visit at 12 m, were assessed by no. of prior ASMs, and by BRV mono vs. polytherapy. Patients with missing data after BRV discontinuation were assigned nonresponse for 50% RR and no SF for SF and CSF.
Results: Analyses by no. of prior ASMs included 1620 patients; 15.4%, 21.9%, 28.8%, and 34.0% had 0–1, 2–3, 4–6, and ≥7 prior ASMs (Table). Patients with ≥7 prior ASMs had longer epilepsy duration vs other ASM subgroups (median, 22.0 vs. 14.0–16.0 years). In all ASM subgroups, median BRV dose at index was 100.0 mg/day (0–1/2–3/4–6/≥7 ASMs: n=246/349/454/542). 50% RRs and rates of SF and CSF at 3, 6, 12 m generally declined as no. of prior ASMs increased (Figure). In patients with 0–1, 2–3, 4–6, and ≥7 ASMs, TEAE incidences at 12 m were 7.0%, 7.4%, 11.5%, 10.0% (n=214/282/356/359);
BRV discontinuations during whole study follow-up were 27.4%, 31.1%, 30.3%, 41.4% (n=248/354/465/548). Analyses by BRV treatment type included 1644 patients (monotherapy: 2.7%, polytherapy: 97.3%; Table). Patients on mono vs. polytherapy had shorter epilepsy duration (median, 9.0 vs. 18.0 years) and fewer prior ASMs (mean, 3.4 vs. 5.5). In both subgroups, median BRV dose at index was 100.0 mg/day (mono: n=45; polytherapy: n=1570). 50% RRs were similar in mono and polytherapy subgroups at 3 m, and numerically higher in the latter at 6 and 12 m. SF and CSF rates at 3, 6, 12 m were numerically higher with mono vs. polytherapy (Figure). In mono and polytherapy subgroups, TEAE incidences at 12 m were 3.8% vs. 9.5% (n=26, 1206); BRV discontinuations during whole study follow-up were 24.4% vs. 33.9% (n=45, 1594).
Conclusions: In this pooled cohort (weighted toward being highly drug-resistant), patients with fewer ASMs before BRV initiation had a numerically higher effectiveness response, but clinically meaningful CSF was seen in all ASM subgroups. TEAE incidences and BRV discontinuations were numerically higher in the ≥7 ASMs subgroup vs. those with fewer ASMs. BRV monotherapy patients had numerically higher SF and CSF vs. polytherapy patients, but clinically meaningful CSF was seen even in the latter; no clear numerical differences were seen in 50% RRs. Patients on mono vs. polytherapy had numerically lower BRV discontinuation.
Funding: Sponsored by UCB Pharma