Safety and effectiveness of stiripentol in patients with Dravet syndrome: A prospective, 3-year, postmarketing surveillance study

Abstract

To conduct a postmarketing surveillance study of patients with Dravet syndrome in Japan to investigate the safety and effectiveness of long-term, real-world, clinical use of stiripentol (STP), an oral antiseizure medication. Dravet syndrome, one of the epilepsy syndromes most resistant to treatment,¹ is characterized by disease onset in the first year of life and repeated episodes of seizures. Developmental delay and ataxia (poor muscle control causing clumsy movements) emerge after the first year of life.

This prospective study was conducted over 156 weeks in all patients with Dravet syndrome who started STP treatment from its launch in Japan in November 2012 until August 2017. Adverse drug reactions (ADRs) were investigated by degree of seriousness. Effectiveness was determined based on a comprehensive assessment by the physician in charge as well as on the percent change in the number of seizures from the pretreatment period.

In total, 520 patients (266 males/254 females; mean age 10 years 6 months; age range 0–50 years) were included in the safety analysis set (all patients taking one dose of the study drug), and 515 patients in the effectiveness analysis set (that compares the costs and effects of alternative health interventions). ADRs occurred in 69.2%, including somnolence (strong desire for sleep or sleeping for unusually long periods), decreased appetite, dizziness, in order of frequency. Twelve deaths occurred, the rate of which was not higher than the reported rates. No new safety concerns were identified. The rate of overall improvement (marked or moderate) after 156 weeks or at treatment discontinuation was 37.7%. Decreases in the number of all seizure types over the long term were confirmed.