Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug (ASD) for partial-onset seizures and primary generalized tonic-clonic seizures. PROVE (NCT03208660; Study 506) was a retrospective, multicenter, non-interventional Phase IV study assessing retention rate, safety, and dosing experience of perampanel administered to patients with epilepsy during routine clinical care. Here, we report results from a subgroup analysis of PROVE, to compare outcomes for patients receiving adjunctive perampanel therapy vs patients receiving perampanel monotherapy. Methods: Data were obtained from medical records of patients who initiated perampanel treatment after January 1, 2014. Follow-up and study completion was on March 15, 2019. Based on the Safety Analysis Set (SAS), the primary endpoint was retention rate (proportion of patients remaining on perampanel at 3, 6, 12, 18, and 24 months following treatment initiation). Efficacy, dosing experience, and safety (monitoring of treatment-emergent adverse events [TEAEs]) were secondary objectives. Adjunctive therapy was defined as perampanel in combination with other ASDs; primary monotherapy was defined as perampanel therapy in the absence of concomitant ASDs; and secondary monotherapy was defined as the conversion from perampanel adjunctive therapy to perampanel monotherapy by withdrawal of concomitant ASDs. Results: Of the overall SAS (N=1693), 1667 (98.5%) patients received adjunctive perampanel (mean [standard deviation (SD)] age, 28.5 [16.5] years; female, 52.7%); 44 (2.6%) received monotherapy (mean [SD] age, 30.0 [19.0] years; female, 54.5%). Patients who received perampanel as both adjunctive therapy and monotherapy (primary, n=29; secondary, n=15) are included in each relevant group. Most patients who had adjunctive perampanel were on 1-3 ASDs at Baseline (n=1260 [75.6%]). At study completion, 811 (47.9%) patients overall had discontinued and 17 (38.6%) had discontinued monotherapy; most common primary reasons for discontinuation were adverse event (overall, n=332 [19.6%]; monotherapy, n=5 [11.4%]) and inadequate therapeutic effect (overall, n=213 [12.6%]; monotherapy, n=5 [11.4%]). Retention rates on perampanel over 24 months for patients receiving adjunctive therapy, primary and secondary monotherapy were 47.0%, 50.0%, and 83.3%, respectively (Figure 1). Mean (SD) cumulative duration of perampanel exposure was 17.0 (15.7) and 14.4 (11.7) months for adjunctive perampanel and monotherapy, respectively. Mean (SD) maximum perampanel dose was lower for adjunctive therapy than for monotherapy (6.6 [3.4] vs 7.2 [2.7] mg, respectively). TEAEs occurred in 665 (39.9%) patients with adjunctive perampanel and 15 (34.1%) with monotherapy (Table 1); dizziness was the most common in both groups. Conclusions: This analysis of PROVE demonstrates that retention rates on perampanel received as either adjunctive therapy or monotherapy are favorable for >=2 years in patients with epilepsy treated during routine clinical care, and similar safety profiles were observed between the two groups. Funding: Eisai Inc.