Abstracts

Rationale:
Brivaracetam (BRV) is indicated for adjunctive treatment of focal (partial-onset) seizures in patients (≥4 years of age) in the European Union (EU) and as monotherapy and adjunctive treatment in the United States. An ongoing 12-month, prospective, non-interventional post-marketing study (EP0077; NCT02687711) is collecting real-world information on patients receiving adjunctive BRV in Europe (prescribed according to routine clinical practice and EU Summary of Product Characteristics).
Method:
We present data from the third interim analysis (cut-off: 28 Nov 2019). Outcomes included 50% responder rates (≥50% reduction from Baseline in focal seizure frequency/28 days) and seizure freedom at 6/12 months. Where part of standard clinical practice of the site, health-related quality of life (QoL; QOLIE-31-P) and Clinical/Patient’s Global Impression of Change (CGIC/PGIC) were assessed. Results535 patients were enrolled, of whom 534 patients had ≥1 BRV dose (mean age: 43.1 years; 52.8% female; mean time since epilepsy diagnosis: 23.0 years; median focal seizures/28 days at Baseline: 4.0; mean number of lifetime [prior and concomitant] antiepileptic drugs [AEDs]: 7.4; 77.9% taking ≥2 concomitant AEDs at study entry). Most common reason for initiating BRV was lack of efficacy of previous treatment (87.1%). Median duration of BRV exposure was 343 days (range 1–618; N=530). At the cut-off date, 360 (67.4%) had completed 6 months observation, 233 (43.6%) had completed 12 months, and 196 (36.7%) patients had discontinued (most common primary reasons: adverse events [13.1%]; lack of efficacy [11.6%]). At 12 months, 50% responder rate was 61.8%, and 11.9% of patients were seizure-free (full analysis set [FAS]); similar results in the modified FAS (Fig. 1). Among patients exposed to BRV, 271/534 (50.7%) had ≥1 treatment-emergent adverse event (TEAE); 140 (26.2%) discontinued due to TEAEs; 183 (34.3%) had TEAEs considered drug-related by investigator, most commonly (≥5%) drug ineffective (6.0%) and seizure (6.0%). One unexpected death was reported (considered not drug-related). Observed mean QOLIE-31-P total score was 51.32 at Baseline (N=230) and 61.47 at 12 months (N=94) (range 0–100; higher scores reflect better functioning). 46.9% of patients had clinically meaningful improvement and 16.0% had clinically meaningful worsening in QOLIE-31-P total score from Baseline to 12 months (Fig. 2). At 12 months (N=122), 67.2% of patients had improvement and 4.9% had worsening in CGIC from Baseline. Similar results were seen in PGIC (62.0% improvement, 9.3% worsening; N=129).
Conclusion:
In this interim analysis, adjunctive BRV was effective and well tolerated in drug-resistant patients in clinical practice in Europe. Observed results for QoL improved over time, possibly due to patients with poor response discontinuing. A numerically higher proportion of patients had improvement than worsening in QOLIE-31-P total score and individual subdomains. The proportion of patients with clinically meaningful changes was maintained over 12 months.
Funding:
:UCB Pharma-sponsored