Authors :
Anna Teresa Giallonardo, 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: 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). The AMPA Study (Study 501; NCT04257604) was a prospective, observational, 12-month study to evaluate the effectiveness, safety, tolerability, and quality of life (QoL) of adjunctive perampanel in routine clinical practice in Italy. We present a post hoc analysis of the final data from AMPA according to perampanel modal dose < 8 mg/day and ≥ 8 mg/day.
Methods: Adult and adolescent patients aged ≥ 12 years with insufficiently controlled FOS, with/without FBTCS, while receiving 1 to 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 50% and 75% responder and seizure-freedom rates, treatment-related adverse events, and QoL
(31-item Quality of Life in Epilepsy Inventory; ≥ 18 years).
Results: In the post hoc Safety Analysis Set, 234 patients received adjunctive perampanel (modal dose < 8 mg/day [low dose], n=155; ≥ 8 mg/day [high dose], n=79); in the Intent-to-Treat Analysis Set, 125 and 77 patients received low- and high-dose perampanel, respectively. Patients had a mean (standard deviation [SD]) age of 40.6 (17.6) and 34.7 (14.0) years, respectively, and received a median (range) of 2 (0–5) and 2 (0–4) concomitant ASMs at baseline, respectively. Median reduction from baseline in seizure frequency (last observation carried forward; LOCF) at Months 6 and 12 was 47.9% (95% confidence interval [CI], 35.8–62.0) and 63.9% (47.3–79.6) for low-dose perampanel, and 63.5% (50.0–72.5) and 70.1% (64.6–81.2) for high-dose perampanel. Compared with high-dose perampanel, low-dose perampanel led to numerically lower 50% responder rates, comparable 75% responder rates, and numerically higher seizure-freedom rates (Figure 1). Mean (SD) QoL scores were similar for low-dose perampanel at baseline and end of treatment (LOCF): 55.1 (17.5) (n=134) and 54.3 (19.9) (n=95), respectively; corresponding data for high-dose perampanel were 58.0 (13.5) (n=73) and 62.3 (15.0) (n=68). Treatment-emergent adverse events were reported in a similar proportion of patients in both groups (Table 1).
Conclusions: These data suggest that many patients with insufficiently controlled FOS, with/without FBTCS, respond to adjunctive perampanel < 8 mg/day, though up-titration to ≥ 8 mg/day may be useful for some patients. QoL was similar in both groups; however, differences in serious adverse events and discontinuations were apparent.
Funding: Eisai S.r.l.