Authors :
Oriano Mecarelli, MD – Sapienza University of Rome, Rome, Italy; Samantha Goldman, MD, B.Sc (Hons) – Eisai Europe Ltd., Hatfield, Hertfordshire, UK; Martina Chiacchiaretta, PhD – Eisai S.r.l., Epilepsy, Milan, Italy; Ricardo Sáinz-Fuertes, LMS, MSc, MRCPsych, PhD – Eisai Europe Ltd., Hatfield, Hertfordshire, UK; Anna Patten, PhD – Eisai Europe Ltd., Hatfield, Hertfordshire, UK; Anna Gentile, PhD – Eisai S.r.l., Epilepsy, Milan, Italy
Rationale: Epilepsy prevalence is higher among older adults compared with younger age groups. Given the progressive aging of the world’s population, epilepsy is set to become more common. In the U.S. and the 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). We present a post hoc analysis of the prospective, observational, 12-month AMPA Study (NCT04257604; Study 501) to assess the effectiveness and safety of adjunctive perampanel in older patients in routine clinical practice in Italy.
Methods: Adult and adolescent patients aged ≥ 12 years with insufficiently controlled FOS, with/without FBTCS, while receiving 1–3 anti-seizure medications (ASMs) were prescribed adjunctive perampanel in line with the approved indication. The treating physician’s decision to prescribe perampanel was made before and independently of their decision to include the patient in the study. The primary endpoint was median
percentage change in seizure frequency per 28 days vs baseline at 6 months (secondary endpoint, Month 12); other secondary efficacy and safety measures included retention rates, 50% and 75% responder and seizure-freedom rates, and monitoring of treatment-related adverse events (TEAEs). This analysis was performed in patients aged ≥ 60 years and by number of baseline ASMs (using last observation carried forward for effectiveness assessments).
Results: Overall, 31 patients were included in this analysis (n=17 [54.8%] male; mean [standard deviation] age 67.8 [6.7] years; Safety Analysis Set). The most common ASM at baseline was carbamazepine (35.5%). Median (95% confidence interval) reductions from baseline in total seizure frequency were 51.7% (19.7–96.8) and 79.5% (25.3–91.4) at 6 and 12 months, respectively (n=22; Table 1). Responder rates increased between 6 and 12 months of treatment (n=22; 50% response: 50.0% to 59.1%; 75% response: 45.5% to 54.5%). Seizure-freedom rates were unchanged at these timepoints (n=23; 21.7%) (Table 1). Retention rates were 48.4% (n=15/31) and 41.9% (n=13/31) at 6 and 12 months, respectively. In general, measures of effectiveness of adjunctive perampanel were numerically greater with 2 baseline ASMs compared with ≥ 3 baseline ASMs, though population size is small (Table 1). TEAEs were reported by 71.0% of patients overall, with decreasing frequency of TEAEs, treatment-related TEAEs, and serious TEAEs by increasing number of baseline ASMs (Table 2).
Conclusions: In this small population of older adults with epilepsy, adjunctive perampanel was effective and well tolerated during routine clinical care. Fewer ASMs at baseline was generally associated with greater effectiveness, in line with expectations that a high number of ASMs may indicate more refractory disease; however, the sample size was small and other factors may also influence the observed differences.
Funding: Eisai S.r.l.