Highlight
• In a 12-month prospective US observational study (EP0088), brivaracetam retention was 57.1% in the full safety population and 72.1% among patients with known treatment status at 12 months, suggesting sustained real-world use.
• Patient-reported outcomes (PROMIS and SERDAS) showed small but early improvements by 1.5 months that were generally maintained to 12 months.
• Almost half of patients experienced at least one treatment-emergent adverse event (TEAE); 16.1% discontinued because of TEAEs. No new safety signals were identified.
Background: clinical context and unmet need
Focal-onset epilepsies are common and frequently refractory: many patients require multiple antiseizure medications (ASMs) before achieving acceptable seizure control. Real-world evidence complements randomized controlled trials by describing tolerability, long-term adherence (retention), and patient-centered outcomes in routine clinical practice, including among patients with prior exposure to other common ASMs such as levetiracetam. Brivaracetam is a selective, high-affinity synaptic vesicle protein 2A (SV2A) ligand approved as adjunctive therapy for focal seizures; it was developed to provide potent SV2A binding with a potentially improved behavioral adverse-event profile relative to levetiracetam.
Study design
EP0088 was a 12-month, prospective, observational study conducted in US clinical practice settings. The study enrolled patients aged ≥16 years with focal-onset seizures who were receiving at least one concomitant ASM and had historical or current exposure to levetiracetam, lamotrigine, oxcarbazepine, and/or carbamazepine. The primary outcome was brivaracetam retention at 12 months following initiation in routine care. Secondary and exploratory assessments included patient-reported outcome (PRO) measures: the Patient-Reported Outcomes Measurement Information System (PROMIS) short forms and the Seizure-Related Disability Assessment Scale (SERDAS). Safety outcomes included incidence of treatment-emergent adverse events (TEAEs), drug-related TEAEs, and discontinuations due to adverse events. The Safety Set (SS) comprised 254 patients who received at least one dose of brivaracetam.
Key findings
Baseline population
254 patients comprised the Safety Set. Mean age was 44.3 years and the median duration of epilepsy was 17.3 years, indicating a population with long-standing disease. Patients had a median of 3.0 historical ASMs and were taking a median of 2.0 concomitant ASMs at brivaracetam initiation, consistent with a difficult-to-treat cohort with substantial prior polytherapy.
Primary outcome: retention at 12 months
Retention at 12 months—a pragmatic proxy for effectiveness and tolerability in real-world studies—was reported in two ways. Using all patients in the Safety Set (including those who dropped out with unknown brivaracetam status), 12-month retention was 57.1% (145/254). In a post hoc analysis limited to patients with known brivaracetam treatment status at 12 months, retention was 72.1% (145/201). The divergence between these figures reflects the impact of missing follow-up data on conservative retention estimates in observational work.
Patient-reported outcomes (PROs)
PROs were assessed using PROMIS short forms (generic health domains) and SERDAS (seizure-related disability). The study reported slight improvements in mean PROMIS T-scores and improvements in mean SERDAS scores by month 1.5, which were generally maintained through 12 months (Full Analysis Set). The magnitude of change was described as small but early and sustained. Specific effect sizes and confidence intervals were not presented in the brief summary; clinicians should interpret the directionality (improvement) as supportive but not definitive evidence of clinically meaningful change without the full numeric data and minimal clinically important difference thresholds.
Safety and tolerability
In the Safety Set, 49.6% of patients reported at least one TEAE, and 38.2% experienced TEAEs considered drug-related. Sixteen point one percent (16.1%) discontinued brivaracetam because of TEAEs. The authors state that no new safety signals were identified. While the specific adverse events are not itemized in the summary provided, prior clinical experience and prescribing information indicate that common AEs for brivaracetam include somnolence, dizziness, fatigue, nausea, and behavioral symptoms; psychiatric adverse events have been observed with SV2A ligands and require monitoring.
Interpretation and clinical relevance
Retention rates of 57% (conservative) to 72% (observed status) at 12 months in a population with long-standing focal epilepsy and exposure to multiple prior ASMs suggest that brivaracetam achieves a meaningful degree of continued use in routine practice. Retention integrates clinicians’ and patients’ judgments about efficacy, tolerability, and convenience and is a pragmatic endpoint in observational studies where seizure diaries and blinded efficacy assessments are not available or standardized.
Early and sustained improvements in patient-reported seizure-related disability (SERDAS) and small improvements in PROMIS domains indicate that some patients perceived functional and health-status benefits shortly after starting brivaracetam. These PROs are valuable complements to clinician-reported outcomes because they reflect daily functioning and quality of life domains important to patients.
The safety findings were consistent with the known tolerability profile of brivaracetam and no novel adverse events emerged. A discontinuation rate of 16% due to TEAEs is clinically relevant and underscores the need to counsel patients about potential side effects and to monitor closely—particularly for behavioral symptoms in patients with prior susceptibility.
Strengths
Prospective collection of data in real-world clinics and the inclusion of PRO instruments strengthen the study’s relevance to clinical practice. The cohort represents a treatment-experienced population, making the findings applicable to patients commonly seen in tertiary and community epilepsy practices who have previously received multiple ASMs, including levetiracetam.
Limitations and points of caution
This observational study lacks a concurrent comparator, so causality about efficacy cannot be established. Retention is influenced by multiple factors beyond antiseizure efficacy, including patient preference, cost, and clinician practice patterns. Missing data and dropouts with unknown treatment status affect the robustness of the conservative retention estimate (57.1%); the post hoc analysis (72.1%) mitigates but does not eliminate this concern.
Details about seizure frequency outcomes, seizure-free rates, or quantitative effect sizes for PRO changes and their statistical significance or clinical meaningfulness were not provided in the summary. Without granular AE listings, it is difficult to compare specific safety events to prior controlled trials. Finally, the cohort’s prior exposure to levetiracetam might influence tolerability and behavioral AE reporting; some patients intolerant to levetiracetam may still experience behavioral AEs with brivaracetam, though brivaracetam’s higher SV2A selectivity has been associated in some studies with a different tolerability profile.
Expert commentary
For clinicians, these data support considering brivaracetam as an adjunctive option for patients with difficult-to-control focal seizures, particularly when prior ASMs have provided inadequate control. Retention in routine practice appears favorable and PRO improvements are encouraging, but treatment choice should remain individualized: consider prior response and tolerability to levetiracetam, comorbid psychiatric history, potential drug–drug interactions with concomitant ASMs, and patient priorities such as cognition and quality of life.
Where possible, practitioners should document baseline PROs and seizure frequency to enable individual assessment of benefit, and they should monitor for neuropsychiatric adverse events—educating patients and caregivers to report mood or behavioral changes promptly.
Conclusion
In this prospective, 12-month observational US study, brivaracetam demonstrated sustained use in a treatment-experienced focal epilepsy population, with early and maintained improvements in patient-reported health and seizure-related disability and a safety profile consistent with prior experience. The data add valuable real-world evidence that complements randomized trials, but limitations inherent in observational designs and missing-data effects temper firm conclusions about magnitude of effect. Clinicians should interpret retention and PRO improvements as supportive signals of clinical utility while continuing individualized assessment and monitoring.
Funding and clinicaltrials.gov
Funding and trial registration details are reported in the primary publication; readers should consult the cited manuscript for the study sponsor and ClinicalTrials.gov identifier (if available) for complete protocol and funding disclosures.
References
1. Dave H, Sperling MR, Altalib HH, Henninger H, Porter RJ, Gelfand M, Dongre P, Elmoufti S, Martin MS, Schulz AL, French JA. Brivaracetam effectiveness and patient-reported outcomes in clinical practice: Data from a 12-month prospective, observational study in the United States. Epilepsy Behav. 2025 Dec;173:110565. doi: 10.1016/j.yebeh.2025.110565. Epub 2025 Jul 3. PMID: 40614390.
2. BRIVIACT (brivaracetam) prescribing information. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/ (accessed date as needed). (Prescribing information provides approved indications, adverse event profile, and recommended dosing.)
Practical takeaways for clinicians
• Consider brivaracetam as an adjunctive option for adults and adolescents (≥16 years in this study) with focal-onset seizures who have had prior ASM exposure, remembering that retention in practice was favorable in this cohort.
• Use baseline and longitudinal PRO instruments when feasible to capture functional change that matters to patients; small early improvements in PROs may herald longer-term benefit.
• Counsel patients about common AEs and the possibility of neuropsychiatric effects, and monitor proactively—particularly if there is prior levetiracetam intolerance or a psychiatric comorbidity.
Suggested next steps in research
Randomized comparative effectiveness studies and registries with standardized seizure-frequency documentation, pre-specified PRO endpoints, and strategies to minimize missing data would further clarify brivaracetam’s place in therapy. Subgroup analyses to identify clinical predictors of retention and PRO improvement (including prior levetiracetam response, psychiatric history, and concomitant ASM regimens) would be particularly valuable.
