Authors :
Laurent Chancharme, PharmD, PhD – Biocodex R&D center, Compiègne, France
Presenting Author: Delphine Vandame, PhD – Biocodex
Yuki Kitamura, MD – Meiji Seika Pharma Co., Ltd
Hiroaki Ohyabu, MD – Meiji Seika Pharma Co., Ltd
Tatsuo Miura, MD – Meiji Seika Pharma Co., Ltd
Naomi Takei-Masuda, MD – Meiji Seika Pharma Co., Ltd.
Daisuke Matsui, MD – Meiji Seika Pharma Co., Ltd.
Yushi Inoue, MD, PhD – NHO Shizuoka Institute of Epilepsy and Neurological Disorders
Yoko Ohtsuka, MD, PhD – Asahigawaso Rehabilitation and Medical Center
Rationale:
Following the market authorization of stiripentol (STP) in Japan in November 2012, a post-marketing surveillance (PMS) study was conducted in real-world settings in all Dravet syndrome (DS) patients who initiated STP. While some results have already been published, the present additional analyses aimed to further assess the long-term safety and effectiveness of STP, with a focus on seizure control across all seizure types, including status epilepticus (SE), and age-related differences in treatment response.Methods:
This prospective study included all patients who initiated STP in Japan between November 2012 and August 2017, followed for up to 156 weeks. Caregivers reported the number of seizures to physicians using a diary, and the incidence of SE was also recorded. Effectiveness was evaluated based on physician-assessed overall improvement (on a 5-point scale), and percentage reduction in seizure frequency was calculated for convulsive, myoclonic, atypical absence, and focal impaired awareness seizures. Safety was assessed through the frequency and severity of adverse drug reactions (ADRs). Subgroup analyses by age at STP initiation were conducted for both efficacy and safety outcomes.Results:
A total of 520 patients were included (mean age: 10.5 years; range: 0–50 years), with 131 patients younger than 3 years and 100 patients aged 19 years or older at treatment initiation. Effectiveness data were available for 480 patients.
Overall, STP led to a median seizure frequency reduction of 64% for convulsive seizures, 100% for generalized myoclonic seizures and/or generalized atypical absence seizures, and for focal impaired awareness seizures over the 156-week period. Notably, the incidence of SE decreased from 31.5% at baseline to 7.1% at year 3, regardless of seizure type.
Across age groups, the highest clinical response was observed in patients under 3 years old, among whom 26% achieved freedom from generalized tonic-clonic (GTC) seizures by the end of the treatment period. In contrast, adults (≥19 years) exhibited a lower response rate, with 14% attaining seizure freedom for GTC seizures. However, seizure reductions were sustained over time across all age groups and seizure types.
ADRs were reported in 69.2% of patients, most commonly somnolence (37.3%) and decreased appetite (26.5%). The incidence of ADRs increased with age (64% in < 3 years vs. 85% in ≥19 years), though no new safety signals emerged. Growth parameters remained within ±2 standard deviations throughout the follow-up period.Conclusions: Stiripentol demonstrated sustained long-term effectiveness in reducing multiple seizure types and status epilepticus over a 3-year period, with an acceptable safety and tolerability profile. Early initiation of STP treatment (< 3 years) was associated with greater clinical benefit and improved tolerability, underscoring the importance of prompt therapeutic intervention in Dravet syndrome.
Funding:
Meiji Seika Pharma Co., Ltd