Abstracts

Rationale: In the U.S. and EU, perampanel is approved for focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥ 4 years (U.S., monotherapy/adjunctive; EU, adjunctive), and generalized tonic-clonic seizures in patients aged ≥ 12 (≥ 7, EU) years (adjunctive). Prior studies have indicated that perampanel exposure levels are reduced among patients who receive EIASMs and may require dose adjustments compared with patients who receive non-EIASMs. Here, we report a post hoc analysis of the prospective, observational 12-month AMPA Study (NCT04257604; Study 501) to assess the effectiveness and safety of perampanel in patients with FOS, stratified by concomitant EIASM use, in routine clinical practice in Italy._x000D_ _x000D_ Methods: Patients aged ≥ 12 years with insufficiently controlled FOS, with/without FBTCS, while receiving 1–3 anti-seizure medications (ASMs) were prescribed adjunctive perampanel per the approved indication. The primary endpoint was median percent reduction from baseline in seizure frequency per 28 days at Month 6 (secondary endpoint, Month 12); other secondary endpoints included 50% and 75% responder rates, seizure-freedom rates, and monitoring of treatment-emergent adverse events (TEAEs) up to 12 months. The outcomes were stratified by baseline EIASM use (defined as carbamazepine, eslicarbazepine, phenytoin, phenytoin sodium, and oxcarbazepine). Last observation carried forward was used to account for missing data for effectiveness assessments._x000D_ _x000D_ Results: The Safety Analysis Set included 234 patients (mean [standard deviation] age, 38.6 [16.7] years; 51.3% female); 131 and 103 patients received EIASMs and non-EIASMs (including two patients not receiving any ASMs) at baseline, respectively. In the Intent-to-Treat Analysis Set, 114 and 88 patients received EIASMs and non-EIASMs, respectively. During Months 6 and 12, median percent reduction from baseline in seizure frequency was 45.3% (95% confidence interval 35.8, 56.3) and 58.0% (47.7, 69.2) with EIASMs, respectively, and 75.0% (54.5, 87.0) and 84.7% (71.4, 90.7) with non-EIASMs, respectively (Figure 1). The responder rates (50%, 75%, and seizure-freedom) were numerically higher in patients with non-EIASMs than EIASMs at Months 6 and 12 (Figure 1). The incidences of TEAEs and treatment-related TEAEs were numerically higher with non-EIASMs compared with EIASMs (Table 1). The most common TEAE was dizziness/vertigo, regardless of EIASM use._x000D_ _x000D_ Conclusions: Consistent with previous reports, these data suggest that adjunctive perampanel is efficacious and well tolerated in patients with insufficiently controlled FOS, with/without FBTCS, regardless of EIASM use. Patients receiving perampanel in combination with an EIASM may require a higher perampanel dose to achieve similar efficacy as with non-EIASMs, likely due to an increased exposure to perampanel among patients who receive non-EIASMs._x000D_ _x000D_ Funding: Eisai s.r.l.