Authors :
Presenting Author: Dulce Campos, MD – University Hospital Clinic, Valladolid, Spain
Anna Lebedeva, MD, PhD – Pirogov Russian National Research Medical University, Moscow, Russia; Sergey Burd, MD – Pirogov Russian National Research Medical University, Moscow, Russia; Stéphane Auvin, MD, PhD, FAES – Robert-Debré University Hospital, APHP, Paris, France; Anna Patten, PhD – Eisai Europe Ltd., Hatfield, Hertfordshire, UK; Ricardo Sáinz-Fuertes, LMS, MSc, MRCPsych, PhD – Eisai Europe Ltd., Hatfield, Hertfordshire, UK
Rationale:
In the US and EU, perampanel is approved for focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures in patients aged ≥ 4 years (US, monotherapy/adjunctive; EU, adjunctive), and generalized tonic-clonic seizures (GTCS) in patients aged ≥ 12 (≥ 7 with idiopathic generalized epilepsy [IGE], EU) years (adjunctive). Some anti-seizure medications (ASMs) can negatively affect cognition. Study 512 (NCT04252846) was a prospective, observational, multicenter, Phase IV study to assess the effectiveness and safety of first adjunctive perampanel in patients aged ≥ 12 years with FOS or GTCS associated with IGE in Europe. Here, we assess the effect of perampanel on cognitive function in patients from Study 512.
Methods:
Patients received perampanel as first adjunctive therapy to ASM monotherapy per the treating physician’s decision. Patients were assessed at baseline and as per routine clinical care, with study visits occurring at six and twelve months. Endpoints included retention rate at 12 months (primary), safety, and cognitive function (which was assessed in adolescents [≥ 12 to < 18 years] using EpiTrack® Junior and adults [≥ 18 years] using EpiTrack® if part of clinical practice). The impact of perampanel on cognitive function was assessed by change from baseline in EpiTrack® scores at six and twelve months, with higher scores indicating better cognitive function.Results:
The Safety Analysis Set (SAS) included 182 patients who received ≥ 1 dose of perampanel and had ≥ 1 post-dose safety measurement; the median (range) age was 36 (12–84) years. In the SAS, a total of 16 patients reported EpiTrack® scores as part of the routine care (adolescents, n=5; adults, n=11). At baseline, the mean (standard deviation [SD]) EpiTrack® scores were 28.0 (7.0) in adolescents and 30.5 (5.0) in adults. At 12 months, the mean (SD) change from baseline in EpiTrack® score was -1.8 (1.9) in adolescents (n=4) and ‑0.6 (4.7) in adults (n=7). Table 1 presents the status of cognitive function based on EpiTrack® scores. Two (50.0%) adolescent patients reported a shift from normal cognitive function at baseline to mild impairment at 12 months; one of whom reported a history of psychiatric disorders at baseline. At 12 months, one (14.3%) adult patient reported a shift from mild impairment at baseline to normal cognitive function, and no adult patients reported a shift to worsened cognitive function. Overall, the incidence of any treatment-emergent adverse event (TEAE) was 52.7% (n=96/182; Table 2); psychiatric TEAEs occurred in 19.8% (n=36/182) of patients with the most common being irritability (8.8%, n=16/182).Conclusions:
First adjunctive perampanel did not show negative effects on cognitive function following 12 months of treatment, although the effect of perampanel varied in adolescents and adults. No new safety signals emerged. These observations were consistent with previous findings; however, interpretation is limited by small sample sizes.Funding:
Eisai Inc.; Eisai Ltd.; Eisai Co., Ltd.