Abstracts

Rationale: Stiripentol (STP) is approved as adjunctive therapy of refractory generalized tonic-clonic seizures (GTCS) in Dravet syndrome (DS), but its off-label use in other refractory epilepsies has been reported (Balestrini et al., Drugs Real World Outcomes 2022, doi: 10.1007/s40801-022-00305-7; Gil-Nagel et al., Epilepsia Open 2024, doi: 10.1002/epi4.12847).




Methods: To analyze the efficacy and safety of STP in refractory pediatric epilepsies, we performed a retrospective single-center analysis of medical records of patients who started STP between January 2014 and January 2024.




Results: 18 DS and 17 non-DS patients initiated STP at median [min-max] ages of 40 [4-179] and 64 [5-180] months, at the median doses of 50 [20-100] and 35 [4-100] mg/kg/d, respectively. Prior STP, DS and non-DS patients had respectively been exposed to a median of 4.5 [1-15] and 9 [4-16] antiseizure medications (ASMs) and, at STP initiation, they were treated with a median of 2 [1-3] and 3 [2-5] concomitant ASMs. STP reduced the seizure frequency by ≥50% in 44.4% DS and 58.8% non-DS patients, by ≥75% in 38.9% DS and 41.2% non-DS patients, and by 100% (seizure freedom) in 11.1% DS and 23.5% non-DS patients. Efficacy of STP was sustained in 90.9% of DS and 69.2% of non-DS patients, and for a median of 87 [5-156] and 12.5 [3-52], respectively. According to seizure type, the number of patients with ≥50% reduction in frequency was (i) DS group: 2/3 (66.7%) for absences, 3/6 (50%) myoclonic, 3/5 (60%) focal and 4/14 (28.6%) with GTCS; (ii) non-DS group: 5/7 (71.4%) in absences, 3/4 (75%) myoclonic, 3/6 (50%) focal, 2/2 (100%) GTCS, 3/9 (33.3%) tonic, and 2/4 (50%) with spasms. None of the patients had worsening of seizures. Five patients (1 with DS, 2 with Lennox-Gastaut syndrome, and 2 with unspecified or structural epileptic and neurodevelopmental encephalopathies]) initiated STP in active status epilepticus (median loading dose of 20 mg/kg/d [6.67-75]; maximum dose from 34 to 100 mg/kg/d), with satisfactory resolution in all of them (median time to resolution of 0.5 days [0.33-14]). STP lead to global and cognitive improvement in 55.6% and 38.9% of DS patients, and in 58.8% and 52.9% of non-DS patients, respectively, whilst 5.6% DS and 23.5% non-DS patients improved their sleep. Adverse events (AEs) occurred in 7/18 (38.9%) DS and 8/17 (47.1%) non-DS patients, with drowsiness being the most frequent (18-22%). Only 3 DS patients presented severe AEs; Two of them, with severe cognitive disorder plus anorexia or instability, discontinued STP after 3-5 months of treatment, with subsequent AE reversion.

Conclusions: STP reduces seizures other than GTCS, not only in patients with DS but also in pediatric patients with non-DS refractory epilepsies, with an additional positive effect on comorbidities.


Funding: With Biocodex support.