Abstracts

Rationale: EP0088 was a multicenter, prospective, observational study of patients initiating brivaracetam (BRV) in the United States (US). The main objective was to assess effectiveness of adjunctive BRV in the real world in adults with focal seizures as measured by retention. Patient-reported outcomes were also evaluated with PROMIS and SERDAS scales as described in a separate publication.

Methods: Patients were enrolled if BRV initiation was planned. Main eligibility criteria included a history of focal seizures, age ≥ 16 years, and lifetime history or current concomitant use of ≥ 1 of four specific antiseizure medications (ASMs): levetiracetam, lamotrigine, oxcarbazepine, or carbamazepine. Information on BRV dose, concomitant ASMs, retrospective seizure data, BRV discontinuation, and adverse events was collected at 1.5-, 3-, 6-, and 12-month follow-up visits. Patients were asked to remain in the study even if BRV treatment was stopped. Retention rates were calculated at 3, 6, and 12 months of BRV exposure.

Results: 304 patients enrolled at 33 sites in the US, of whom 254 initiated BRV. Median time since epilepsy diagnosis was 17.3 years. Focal onset epilepsy was diagnosed in 95.2% of patients with seizure classification data. Most patients (83.6%) had ≥ 1 seizure during the 6-month retrospective Baseline Period. Historical ASMs were reported for 82.7% of all patients (mean: 3.3). Concomitant ASMs were reported in 94.5% of patients (mean: 2.3). 162/254 patients completed the study (Table 1). 59 patients discontinued BRV, mainly due to side effects. 57.1% of patients were exposed to BRV for ≥ 311 days and 28.0% for < 90 days. The most frequent BRV starting doses were ≥ 100 mg/d to < 150 mg/d (48.4%) and ≥ 50 mg/d to < 100 mg/d (34.3%). BRV modal daily doses were ≥ 100 mg/d to < 150 mg/d in 31.5% and 200 mg/d in 27.6% of patients. Retention of patients in the study on BRV was 183/254 (72.0%; 95% confidence interval: 66.1–77.5) at 3 months, 164/254 (64.6%; 58.3–70.4) at 6 months, and 145/254 (57.1%; 50.8–63.3) at 12 months. 92 patients (36.2%) dropped out of the study; the most frequent primary reasons were “consent withdrawn” (42.4%) and “lost to follow-up” (35.9%). 44/157 (28.0%) of patients on BRV reported seizure freedom for 6 months at Month 12 compared with 16.4% during retrospective baseline. Treatment-emergent adverse events (TEAEs) from all causes were reported in 128/254 (50.4%) patients. In 100 (39.4%) patients TEAEs were considered drug-related by the investigator. 54 (21.3%) patients experienced serious TEAEs. 41 (16.1%) patients discontinued BRV due to TEAEs. The most common TEAEs leading to BRV discontinuation were fatigue (3.1%), dizziness (2.0%), headache (1.6%), and irritability (1.6%). Two serious adverse events led to death; one additional event with fatal outcome occurred 99 days after the last BRV dose. None of these deaths were considered BRV-related.

Conclusions: BRV was well tolerated and effective in one of the first US real-world evidence studies examining BRV in a real-world setting, as reflected by a 12-month retention of 57.1%.

Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded; partnership between UCB Pharma, Epilepsy Study Consortium, and PRA.