Rationale:
To evaluate the long-term efficacy and tolerability of add-on Stiripentol (STP) treatment in different forms of refractory epilepsies.
Method:
We reviewed medical records of all patients with drug-resistant epilepsies treated with STP as add-on therapy at Meyer Children’s Hospital from January 2007 to January 2020. The drug scheme administration consisted of a starting dose of STP of 10-15 mg/kg/day up to maximum of 50 mg/kg/day based on age and weight, with increments every week. Etiology of epilepsy was classified as structural, immune-infectious, metabolic, genetic [including Dravet syndrome (DS) and other genetic epilepsies]; types of epilepsy were categorized as focal, generalized or combined; types of seizures were classified as focal, secondarily generalised (SGS), generalized tonic-clonic (GTCS), and other generalized seizures (GS). Patients achieving 50% or higher reduction of baseline seizure frequency were considered to be “responders”; those with reduction < 50% or experiencing no change or worsening of seizure frequency were instead “non-responders”. Retention rate was defined as the probability of continuing STP with no change in therapy regimen. Tolerability was assessed by reporting adverse events.
Results:
A total of 193 patients aged 5 months - 46 years received add-on STP, including 38 patients with DS. The median follow-up age was 12.2 months (range = 15 days, 19 years; interquartile range=29 months). 47 patients received more than 2 AEDs with Clobazam being the most commonly used add-on medication. 101 patients (52.3%) were responders; 18 of them (9.3% of the whole population; 17.8% of responders) became seizure-free. Responders’ rates (RR) were higher in the “genetic etiology” group (61.9%), especially in DS (65.8%). With respect to seizure type, the best RR were observed in patients with generalized tonic-clonic seizures (72.7%) and in those with focal seizures without tonic clonic seizures (46.9%) (Table 1). The median relapse-free survival was 33.5 months in the 101 responders (Table 2a). Patient with DS showed a probability to remain responder 41.3% after 240 months of follow-up. The median time to STP failure was 44.6 months in the whole series (Table 2b). Overall, a higher retention rate was observed in patients with a shorter duration of disease, in DS and in those treated with ≤2 AEDs. Adverse events (AE) were observed in 39 patients (19.4%), leading STP discontinuation in 4 (5.5%). The most frequently AEs were neurological (12.9%) and gastrointestinal (2.5%).
Conclusion:
This study confirms the long-term efficacy of STP as add-on therapy in patients with different types of drug-resistant epilepsies. Additional prospectively designed studies are required to confirm STP efficacy of focal epilepsy.
Funding:
:none
FIGURES
Figure 1