Long-term safety and effectiveness of stiripentol in patients with Dravet syndrome: Interim report of a post-marketing surveillance study in Japan.


Journal

Epilepsy research
ISSN: 1872-6844
Titre abrégé: Epilepsy Res
Pays: Netherlands
ID NLM: 8703089

Informations de publication

Date de publication:
02 2021
Historique:
received: 30 07 2020
revised: 07 12 2020
accepted: 14 12 2020
pubmed: 4 1 2021
medline: 10 2 2022
entrez: 3 1 2021
Statut: ppublish

Résumé

A post-marketing surveillance study is investigating the safety and effectiveness of stiripentol during real-world clinical use in Japanese patients with Dravet syndrome (DS). The safety and effectiveness of stiripentol were prospectively investigated over 104 weeks in all patients with DS who were administered the drug from November 2012 through July 2019 in Japan. Patients administered stiripentol for the first time after its approval were defined as "new patients," and those who continued to take the drug after participating in domestic clinical studies were defined as "continuous-use patients." The responder rate was defined as the proportion of patients with a ≥50 % decrease in seizure episodes at the time of assessment of stiripentol effectiveness compared with the 4 weeks before starting stiripentol. Overall improvement was evaluated by the physician in charge based on the comprehensive assessment of the patient's condition after stiripentol treatment. Of 411 patients whose information was collected, 410 patients (376 new and 34 continuous-use) were included in the safety analysis set, and 409 (376 new and 33 continuous-use) were included in the effectiveness analysis set. The median age of new patients was 7 years (range: 0.5-50 years) at the time of stiripentol initiation; 99 % of patients were taking concomitant sodium valproate and 93 % clobazam. Adverse drug reactions occurred in 70 % of new patients; the most common were somnolence (39 %) and loss of appetite (25 %). No new safety concerns due to stiripentol were observed. The responder rate in new patients was 43 % (110/257 patients) for convulsive seizures (tonic-clonic and/or clonic convulsions), 55 % (58/105 patients) for focal impaired awareness seizures, and 62 % (56/90 patients) for generalized myoclonic seizures and/or generalized atypical absence seizures. Overall improvement (after 104 weeks or at the time of drug discontinuation) was rated as marked or moderate in 160/353 of new patients (45 %). Stiripentol is safe and effective during long-term use in patients with DS in routine clinical practice.

Sections du résumé

BACKGROUND
A post-marketing surveillance study is investigating the safety and effectiveness of stiripentol during real-world clinical use in Japanese patients with Dravet syndrome (DS).
METHODS
The safety and effectiveness of stiripentol were prospectively investigated over 104 weeks in all patients with DS who were administered the drug from November 2012 through July 2019 in Japan. Patients administered stiripentol for the first time after its approval were defined as "new patients," and those who continued to take the drug after participating in domestic clinical studies were defined as "continuous-use patients." The responder rate was defined as the proportion of patients with a ≥50 % decrease in seizure episodes at the time of assessment of stiripentol effectiveness compared with the 4 weeks before starting stiripentol. Overall improvement was evaluated by the physician in charge based on the comprehensive assessment of the patient's condition after stiripentol treatment.
RESULTS
Of 411 patients whose information was collected, 410 patients (376 new and 34 continuous-use) were included in the safety analysis set, and 409 (376 new and 33 continuous-use) were included in the effectiveness analysis set. The median age of new patients was 7 years (range: 0.5-50 years) at the time of stiripentol initiation; 99 % of patients were taking concomitant sodium valproate and 93 % clobazam. Adverse drug reactions occurred in 70 % of new patients; the most common were somnolence (39 %) and loss of appetite (25 %). No new safety concerns due to stiripentol were observed. The responder rate in new patients was 43 % (110/257 patients) for convulsive seizures (tonic-clonic and/or clonic convulsions), 55 % (58/105 patients) for focal impaired awareness seizures, and 62 % (56/90 patients) for generalized myoclonic seizures and/or generalized atypical absence seizures. Overall improvement (after 104 weeks or at the time of drug discontinuation) was rated as marked or moderate in 160/353 of new patients (45 %).
CONCLUSION
Stiripentol is safe and effective during long-term use in patients with DS in routine clinical practice.

Identifiants

pubmed: 33388609
pii: S0920-1211(20)30586-6
doi: 10.1016/j.eplepsyres.2020.106535
pii:
doi:

Substances chimiques

Anticonvulsants 0
Dioxolanes 0
Pharmaceutical Preparations 0
stiripentol R02XOT8V8I

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106535

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Miyuki Yamada (M)

Safety Vigilance & Management Dept., Reliability & Quality Assurance Division, Meiji Seika Pharma Co., Ltd., Tokyo, Japan. Electronic address: miyuki.yamada@meiji.com.

Katsuyoshi Suzuki (K)

Safety Vigilance & Management Dept., Reliability & Quality Assurance Division, Meiji Seika Pharma Co., Ltd., Tokyo, Japan. Electronic address: katsuyoshi.suzuki.aa@meiji.com.

Daisuke Matsui (D)

Safety Vigilance & Management Dept., Reliability & Quality Assurance Division, Meiji Seika Pharma Co., Ltd., Tokyo, Japan. Electronic address: daisuke.matsui@meiji.com.

Yushi Inoue (Y)

Department of Clinical Research, National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan. Electronic address: yinoue-jes@umin.net.

Yoko Ohtsuka (Y)

Department of Child Neurology, Asahigawaso Rehabilitation and Medical Center, Okayama, Japan. Electronic address: ohtsuka@okayama-u.ac.jp.

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Classifications MeSH