Authors :
Presenting Author: Motoki Inaji, MD,PhD – Tokyo Medical and Dental University
Yukika Arai, MD – Tokyo Medical and Dental University; Kazuhide Shimizu, MD, PhD – Tokyo Medical and Dental University; Satoka Hashimoto, MD, PhD – Tokyo Medical and Dental University; Shinji Yamamoto, MD, PhD – Tsuchiura Kyodo Generals Hospital; Taketoshi Maehara, MD, PhD – Tokyo Medical and Dental University
Rationale: Perampanel (PER) is a newly developed AMPA receptor antagonist and has been globally approved for
treating both focal and generalized seizures. The efficacy and safety of PER were reported in only a short period. This study aims to clarify the long-term efficacy and safety of PER as an add-on therapy.
Methods: This retrospective observational study involved 176 patients who received medical therapy with PER as add-on therapy between June 2016 and July 2022 in two Japanese epilepsy centers. We evaluated the adherence, seizure frequency, and plasma concentration at three time points; 6, 12, and 24 months and more after starting adjunctive PER treatment, respectively. The institutional review board at both institutes approved the study. (M2022-263).
Results: One hundred twelve patients and eighty six patients were evaluated at the six and twelve months checkpoints, and fifty two patients reached at the last checkpoints. Overall 42.9% (48/112), 45.4% (40/86), and 44.2% (23/52) of patients were seizure-free at six months, 12 months, and 24 months and over. The tolerance rate of PER was 78.3% at six months, 69.9% at 12 months, and 54.7% at 24 months and over following treatment. At 24 months and over, seizure free group was taking a significantly lower dose of PER than the seizure remnant group. Furthermore, the number of anti-seizure medications (ASMs) was associated with seizure outcomes. In addition, free rate was significantly higher when PER was used as a first add-on than a late add-on. There was no significant difference in plasma concentration between the seizure-free group and the seizure-remnant group at 24 months and over. Still, in using PER dose of 2mg, plasma concentrations were significantly higher in the seizure-free group than in the seizure-remnant group (282.7 ± 109.8 vs 94.7 ± 54.9, p=0.0024).
Conclusions: This retrospective observational study provides evidence of PER's efficacy and safety in Japanese patients over 24 months and longer. Notably, patients initiating PER as a first add-on showed a better seizure outcome than a late add-on in long-term. Measuring plasma concentration can be effective for patients who are controlled with low doses of PER.
Funding: This work was supported by JSPS KAKENHI Grant Number 20K09341.