Abstracts

This is a Late Breaking abstract

Rationale: This French retrospective study aimed at evaluating the short- and long-term effects of stiripentol (STP) when initiated in Dravet syndrome (DS) patients before the age of 2 years.

Methods: Data were extracted from 4 cohort databases: two successive cohorts (before and after 2005) from the Paris reference center for rare epilepsies (CREER1 and CREER2), the STP temporary authorization for use (TAU) (Biocodex 2006), and the STP post-marketing survey (PMS) (Biocodex 2012). Data regarding generalized convulsive seizures (GCS) frequency, adverse events (AE) and antiseizure medications were collected before STP initiation (3 month-baseline), at short-term ( < 6 months on STP) and long-term (last visit on STP). GCS duration was also collected in CREER1/CREER2 and split up into short seizures (≤ 5 minutes), status epilepticus (SE) (5-30 minutes) and long SE (> 30 minutes).

Results: Data from 131 patients were considered: 24 CREER1, 27 CREER2, 46 TAU, 34 PMS. Overall, STP was initiated at a median (med) age of 12.6 months (m), at the median dose of 50 mg/kg/day. Noteworthy, STP was initiated at a younger age (med 11 vs. 15 m) and at a lower dosage (med 50 vs. 65 mg/kg/day) in the recent CREER2 cohort than in CREER1. In 93% of cases valproate (med 24 mg/kg/day) and clobazam (med 0.5 mg/kg/day) were associated to STP. _x000D_
At short-term (med age, 16.2 m), GCS frequency was decreased (p < 0.01), 52% of the patients were responders (≥ 50% decrease in GCS) and 31% were GCS free. Further STP initiation, both SE and long SE decreased in frequency (p < 0.01) and stopped in 61% and 55% of the patients respectively. At long-term (med age, 40.5 m) the reduced frequency of SE and long SE was maintained (p < 0.01 compared to baseline) and even reinforced (p < 0.05 compared to short-term). Similarly, the frequency of monthly hospitalizations decreased from 58% at baseline to 38% at short-term and 11% at long-term. _x000D_
Short seizures frequency increased between short and long-term, despite additional comedications in 26% of the patients (topiramate n=19, cannabidiol n=4, fenfluramine n=1). _x000D_
From a safety perspective, three patients (2%) died from SUDEP during the follow-up. Forty-two percent of patients experienced at least one AE, mainly loss of appetite/weight (21%), agitation/sleep disorders (17%), and somnolence/hypotonia (15%). Asymptomatic neutropenia and thrombopenia were reported in 5 and 4 cases respectively. AE led to STP discontinuation in 3 patients. Overall, safety information collected in children below 2 y was in accordance with the well-known safety profile of STP in older patients.

Conclusions: This real-world study showed that initiating STP before 2 y of age is highly beneficial to DS patients: the frequency of GCS significantly decreased, and around one third of patients became seizure free. More importantly, the duration of GCS significantly decreased with less life-threatening episodes of SE and less hospitalizations, having a large impact on the quality of life of patients and caregivers.

Funding: This study was supported by Biocodex.