Real-world Outcomes in Patients on Concomitant Levetiracetam at Brivaracetam Initiation: Post Hoc Analysis by Levetiracetam Discontinuation Status
Abstract number :
3.304
Submission category :
7. Anti-seizure Medications / 7E. Other
Year :
2022
Submission ID :
2204040
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:23 AM
Authors :
Michael Gelfand, MD, PhD – University of Pennsylvania, Philadelphia, Pennsylvania, US; Heidi Henninger, MD – Maine Medical Center, Portland, Maine, US; Hina Dave, MD – University of Texas Southwestern Medical Center, Dallas, Texas, US; Michael Sperling, MD – Thomas Jefferson University, Philadelphia, PA, US; Hamada Altalib, DO, MPH – Yale School of Medicine, Yale University, New Haven, Connecticut, US; Roger Porter, MD – Department of Neurology – University of Pennsylvania, Philadelphia, PA, US; Anne-Liv Schulz, MD – UCB Pharma, Monheim am Rhein, Germany; Prashant Dongre, MD – UCB Pharma, Smyrna, Georgia, US; Sami Elmoufti, MSc – UCB Pharma, Morrisville, North Carolina, US; Melinda Martin, PhD – UCB Pharma, Smyrna, Georgia, US; Svetlana Dimova, MD, PhD – UCB Pharma, Brussels, Belgium; Jacqueline French, MD – NYU Comprehensive Epilepsy Center, NYC, NY, US
Rationale: Previous real-world data (EP0088) indicated that brivaracetam (BRV) short- and long-term retention was similar across patients on concomitant levetiracetam (LEV), lamotrigine, oxcarbazepine, and carbamazepine (Dave H, et al. AES 2021; abstract 2.203). As the BRV label indicates no added therapeutic benefit of combining LEV and BRV, we further evaluated outcomes and characteristics of patients on concomitant LEV at BRV initiation.
Methods: Post hoc analysis of a 12-month, prospective, noninterventional, multicenter U.S. study in patients (≥16 years) with history of focal seizures (EP0088). Outcomes were analyzed in patients on concomitant LEV at BRV initiation and in subgroups by LEV discontinuation status.
Results: A total of 118 patients on concomitant LEV at BRV initiation were included: mean age 44.0 years; 46.6% male; mean epilepsy duration 21.2 years; mean number of historical and concomitant antiseizure medications (ASMs) 2.6 and 2.5, respectively. 24.6% did not report seizures during 6-month retrospective baseline. Most common reasons for BRV initiation were lack of efficacy of current treatment (53.4%), behavioral side effects (45.8%), or other intolerance (15.3%). Comparing patients who discontinued LEV during BRV treatment (n=59) and patients who retained LEV with BRV until last assessment (n=59), baseline characteristics, reasons for BRV initiation, BRV starting dose, and BRV modal dose were similar. BRV retention at 12 months was 63.6% (95% CI: 54.2, 72.2) in all concomitant LEV patients, 72.9% (59.7, 83.6) in those discontinuing LEV, and 54.2% (40.8, 67.3) in those remaining on LEV. 78% patients discontinuing LEV did so within the first 30 days (Figure 1A). Patients who discontinued LEV were less likely to discontinue BRV (Figure 1B). Seizure freedom during the last 6 months of BRV treatment (patients with ≥12 months BRV treatment) was 33.8% (26/77) in all patients, 33.3% (15/45) in those discontinuing LEV, and 34.4% (11/32) in those remaining on LEV. In patients discontinuing LEV, 67.8% did not have a change in other concomitant ASMs and 16.9% removed ≥1 ASM without adding ASMs (Figure 2). In patients continuing LEV, the majority (86.4%) had a stable concomitant ASM regimen, and especially a stable LEV dose. Overall, 46.6% reported treatment-emergent adverse events (TEAEs), 25.4% drug-related, 16.9% serious, 4.2% behavioral TEAEs (BAEs), 7.6% discontinued due to TEAE, and 0.8% discontinued due to BAEs. The BRV tolerability profile, including BAEs, was generally similar in patients who discontinued vs those who remained on LEV (BAEs 3.4% vs. 5.1%).
Conclusions: In this post hoc analysis, half of patients on LEV at BRV initiation discontinued LEV, primarily during the first month after BRV initiation. The remaining 50% of patients who continued on a stable dose of LEV had a lower BRV retention than patients who discontinued LEV. In patients remaining on BRV for ≥12 months, the proportion of seizure-free patients was similar irrespective of LEV discontinuation status. In patients on concomitant LEV at BRV initiation, BRV was well tolerated with low rates of BAEs independent of LEV discontinuation status during BRV treatment.
Funding: Sponsored by UCB Pharma
Anti-seizure Medications