Abstracts

Rationale: To evaluate retrospectively the short and long-term effect of initiating stiripentol before 2y in patients with Dravet syndrome from the cohort-databases available in France.

Methods: We selected databases of Dravet patients treated with stiripentol since 1991 and included those that fulfilled the following criteria: stiripentol initiated before 2y of age, longitudinal data available, acquired in France, acquired within the framework of a regulatory protocol or published and raw data fully accessible. We included 3 databases: (1) the temporary authorization for use (TAU) collected by Biocodex in 2006, (2) the European post-marketing survey (PMS) collected by Biocodex in 2012 and (3) the two successive cohorts of Dravet patients from our reference center for rare epilepsies (CREER) in Paris already reported (Perez et al 1999, Thanh et al 2002, Chiron et al 2018, Nabbout et al 2020). We eliminated the duplicates. We extracted the data on seizures, treatments and patient’s condition at stiripentol initiation, at short-term stiripentol before 2y of age, and at long-term last visit. We completed, when necessary, the missing data of patients that have their data accessible at CREER.

Results: Altogether there were 160 patients who received stiripentol before 2y, 52 in TAU, 34 in PMS, 74 in CREER (28 in the oldest cohort, 46 in the most recent). Stiripentol was initiated at a mean age of 15 months, with valproate and clobazam as comedication in 96% of cases. Among the available short-term data, the responder rate (50% decrease in convulsive seizure frequency) before 2y of age ranged from 54% and 84%, seizure duration and the number of status epilepticus were significantly reduced, and tolerability was good (23 severe adverse events in TAU and PMS, but unrelated to stiripentol, and 2 patients withdrawn for related neutropenia).

At last visit, at a median of 4.5y (respectively 2.7y, 3.4y, 7.2y), there were still 94% of patients on stiripentol (respectively 98%, 91%, 92%), 95% on valproate, 90% on clobazam and 35% on topiramate as additional comedication; respectively 21% and 18% of the recent CREER cohort also received cannabidiol or fenfluramine. Safety was acceptable, loss of appetite and somnolence being the main adverse events. Stiripentol had to be discontinued for poor tolerance in respectively 2%, 3% and 8% of cases.

Conclusions: We were able to gather a large cohort of 160 patients with Dravet syndrome treated with stiripentol before the age of 2 years according to a homogeneous procedure in one country (doses, comedications). Such methodology should be further used to capitalize on the real word data with such a medication. Preliminary results are in favor of an efficiency and a tolerability at least as good as those reported in children treated over 2 years old.

Funding: Please list any funding that was received in support of this abstract.: This study was supported by Biocodex.