Authors :
Presenting Author: Louis-Georges Maillard, MD, PhD – Klinik für Neurologie, Marburg, Germany
First Author: Susanne Knake, MD – Epilepsy Centre Hessen, Philipps-University Marburg, Marburg, Germany
Marco De Curtis, MD – Epilepsy Units, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Eliane Kobayashi, MD, PhD – Montreal Neurological Institute and Hospital, Montreal, Canada; Teresa Lema-Facal, MD – Coruna University Hospital, A Coruna, Spain; Bonita Rehel, MSc – UCB Pharma, Oakville, Ontario, Canada; Sylvain Rheims, MD, PhD – Department of Functional Neurology and Epileptology, Hospices Civils de Lyon and Lyon 1 University, Lyon, France; Anne-Liv Schulz, MD – UCB Pharma, Monheim am Rhein, Germany; Iryna Leunikava, MSc – UCB Pharma, Monheim am Rhein, Germany
Rationale:
This was a planned interim analysis of ongoing, prospective, noninterventional study (BRITOBA; EP0103) to evaluate effectiveness of adjunctive brivaracetam (BRV) in earlier treatment lines in adults with focal-onset seizures (FOS) for up to 12 months (mos).
Methods:
BRITOBA is a postmarketing study at 81 clinical/office-based sites in Europe and Canada prescribing BRV per standard practice. Selection criteria: age ≥18 years, history of FOS (with/without focal to bilateral tonic-clonic seizures [FBTCS]), no BRV treatment before study entry, ≥1 antiseizure medication (ASM) at BRV initiation, ≤3 lifetime (prior and at BRV initiation) ASMs. Patients are observed for up to ~12 mos. Endpoints: seizure freedom (SF) for ≥6 consecutive mos (primary), ≥50% response in FOS reduction (all types of FOS), Clinical and Patient’s Global Impression of Change (CGIC; PGIC), treatment-emergent adverse events (TEAEs).
Results:
At time of data snapshot (June 3, 2022), 252 patients had received
≥1 dose of BRV (Safety Set; SS. of these, 176 were included in the Per Protocol Set (PPS). In the SS, mean age at baseline was 45.4 years (n=252) (PPS: 46.4 years [n=176]), mean time since epilepsy diagnosis was 13.24 years (n=249) (PPS: 13.59 years [n=176]), mean FOS frequency was 4.07 seizures/28 days (n=245) (PPS: 4.74 seizures/28 days [n=175]), 35% of patients (n=251) had FBTCS at baseline (PPS: 41% [n=176]), and mean number of lifetime ASMs was 1.9 (n=247) (PPS: 2.0 [n=176]). Mean/median BRV dose (SS) was 81.8/100.0 mg/day (n=249) at visit 1 (PPS: 88.6/100.0 mg/day [n=175]) and 128.7/100.0 mg/day (n=41) at 12 mos (PPS: 137.1/125.0 mg/day [n=31]). In the SS, 174 (69.0%) patients completed the 3-mo visit (PPS: 126 [71.6%]), 97 (38.5%) completed the 6-mo visit (PPS: 65 [36.9%]), and 42 (16.7%) completed the 12-mo visit (PPS: 31 [17.6%]). For patients in the SS who completed the 12-mo period and had available data, 51.4% (18/35) were SF for ≥6 consecutive mos (Fig 1A); ≥50% reduction from baseline in FOS frequency was 74.7%, 70.9%, and 73.2% at 6, 9, and 12 mos, respectively (Fig 1B). Similar outcomes were observed in the PPS (Fig 1A-B). In the SS, median percent reduction in FOS frequency was ≥89.9% at 6, 9, and 12 mos (≥83.3% in PPS). For CGIC (SS), improvement (very much or much improved) was reported in 42.0% (71/169), 48.4% (44/91), and 51.2% (21/41) of patients at 3, 6 and 12 mos, respectively. For PGIC (SS), improvement (very much or much improved) was reported in 36.4% (47/129), 37.3% (22/59) and 55.0% (11/20) patients at 3, 6, and 12 mos, respectively. Similar outcomes were observed in the PPS (Fig 2A-B). In the SS, 35 (13.9%) patients reported TEAEs (PPS: 19 [10.8%]), 24 (9.5%) reported drug-related TEAEs (PPS: 12 [6.8%]), and 12 (4.8%) discontinued due to TEAEs (PPS: 6 [3.4%]). One patient had a serious TEAE (irritability).
Conclusions:
In this first interim analysis of BRITOBA, adjunctive BRV was effective and well tolerated in adults with FOS in earlier treatment lines (median of 2 lifetime ASMs). Funding: UCB Pharma-sponsored