Long-term efficacy and safety of perampanel as an add-on therapy in patients with epilepsy
Copyright © 2024 Elsevier B.V. All rights reserved..
BACKGROUND: Perampanel (PER) is a newly developed amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist that has been globally approved for the treatment of both focal and generalized seizures. The efficacy and safety of PER have only been reported over short periods of treatment so far. This study aims to clarify the long-term efficacy and safety of PER as an add-on therapy.
METHOD: This retrospective observational study investigated 176 epilepsy patients who received PER as add-on medical therapy in two Japanese epilepsy centers between June 2016 and July 2022. The adherence, seizure frequency, and plasma concentration of PER were evaluated at three time points: 6 months, 12 months, and 24 months or longer after the start of adjunctive PER treatment.
RESULTS: 112 patients undergoing PER treatment were evaluated at 6 months, 86 were evaluated at 12 months, and 52 were evaluated at 24 months or longer. Overall, 42.9 % (48/112), 45.4 % (40/86), and 44.2 % (23/52) of the patients were seizure-free at 6, 12, and 24 months or longer, respectively. The rate of PER tolerance was 78.3 %, 69.9 %, and 54.7 % at 6, 12, and 24 months or longer, respectively. At the latest timepoint, the seizure-free group was taking a significantly lower dose of PER than the seizure-remnant group, and the number of anti-seizure medications (ASMs) was associated with seizure outcomes. In addition, the seizure-free rate was significantly higher in patients who received PER as a first add-on than in those who received it as a late add-on. No significant difference was found in the plasma concentration of PER between the seizure-free and seizure-remnant groups at 24 months or longer. Among the patients receiving PER at dose of 2 mg, however, the plasma concentrations were significantly higher in the seizure-free group than in the seizure-remnant group (282.7 ± 109.8 μg/ml vs 94.7 ± 54.9 μg/ml, p = 0.0024).
CONCLUSION: This long-term retrospective observational study provides evidence of the efficacy and safety of PER over 2 years treatment period in Japan. Notably, patients who started on PER as the first add-on showed a better seizure outcome than those who received it as a late add-on over the long term. Measured plasma concentrations may provide valuable guidance for the management of patients. Higher plasma concentration at low dose PER may suggest the better seizure control.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:200 |
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| Enthalten in: |
Epilepsy research - 200(2024) vom: 27. Feb., Seite 107307 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Arai, Yukika [VerfasserIn] |
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| Links: |
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| Themen: |
Add-on therapy |
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| Anmerkungen: |
Date Completed 23.02.2024 Date Revised 23.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.eplepsyres.2024.107307 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367764490 |
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| 100 | 1 | |a Arai, Yukika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Long-term efficacy and safety of perampanel as an add-on therapy in patients with epilepsy |
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| 500 | |a Date Revised 23.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Perampanel (PER) is a newly developed amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist that has been globally approved for the treatment of both focal and generalized seizures. The efficacy and safety of PER have only been reported over short periods of treatment so far. This study aims to clarify the long-term efficacy and safety of PER as an add-on therapy | ||
| 520 | |a METHOD: This retrospective observational study investigated 176 epilepsy patients who received PER as add-on medical therapy in two Japanese epilepsy centers between June 2016 and July 2022. The adherence, seizure frequency, and plasma concentration of PER were evaluated at three time points: 6 months, 12 months, and 24 months or longer after the start of adjunctive PER treatment | ||
| 520 | |a RESULTS: 112 patients undergoing PER treatment were evaluated at 6 months, 86 were evaluated at 12 months, and 52 were evaluated at 24 months or longer. Overall, 42.9 % (48/112), 45.4 % (40/86), and 44.2 % (23/52) of the patients were seizure-free at 6, 12, and 24 months or longer, respectively. The rate of PER tolerance was 78.3 %, 69.9 %, and 54.7 % at 6, 12, and 24 months or longer, respectively. At the latest timepoint, the seizure-free group was taking a significantly lower dose of PER than the seizure-remnant group, and the number of anti-seizure medications (ASMs) was associated with seizure outcomes. In addition, the seizure-free rate was significantly higher in patients who received PER as a first add-on than in those who received it as a late add-on. No significant difference was found in the plasma concentration of PER between the seizure-free and seizure-remnant groups at 24 months or longer. Among the patients receiving PER at dose of 2 mg, however, the plasma concentrations were significantly higher in the seizure-free group than in the seizure-remnant group (282.7 ± 109.8 μg/ml vs 94.7 ± 54.9 μg/ml, p = 0.0024) | ||
| 520 | |a CONCLUSION: This long-term retrospective observational study provides evidence of the efficacy and safety of PER over 2 years treatment period in Japan. Notably, patients who started on PER as the first add-on showed a better seizure outcome than those who received it as a late add-on over the long term. Measured plasma concentrations may provide valuable guidance for the management of patients. Higher plasma concentration at low dose PER may suggest the better seizure control | ||
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Add-on therapy | |
| 650 | 4 | |a Anti-seizure medicines | |
| 650 | 4 | |a Epilepsy | |
| 650 | 4 | |a Perampanel | |
| 650 | 7 | |a perampanel |2 NLM | |
| 650 | 7 | |a H821664NPK |2 NLM | |
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| 650 | 7 | |a Amino Acids |2 NLM | |
| 650 | 7 | |a Excitatory Amino Acid Antagonists |2 NLM | |
| 650 | 7 | |a Nitriles |2 NLM | |
| 700 | 1 | |a Inaji, Motoki |e verfasserin |4 aut | |
| 700 | 1 | |a Shimizu, Kazuhide |e verfasserin |4 aut | |
| 700 | 1 | |a Kondo, Shizukoto |e verfasserin |4 aut | |
| 700 | 1 | |a Hashimoto-Fujimoto, Satoka |e verfasserin |4 aut | |
| 700 | 1 | |a Kiyokawa, Juri |e verfasserin |4 aut | |
| 700 | 1 | |a Kawano, Yoshihisa |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Shinji |e verfasserin |4 aut | |
| 700 | 1 | |a Maehara, Taketoshi |e verfasserin |4 aut | |
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