Real-world Dravet cohort links FFA to fewer status episodes

PURPOSE: Status epilepticus (SE) is a major contributor to morbidity in Dravet syndrome (DS). The impact of recently introduced anti-seizure medications (ASMs)-stiripentol (STP), fenfluramine (FFA), and cannabidiol (CBD)-on SE burden remains incompletely defined. We aimed to characterize acute SE management and evaluate the association between these therapies and SE outcomes. METHODS: In this multicenter retrospective cohort study, patients with genetically confirmed DS were included. Clinical data, SE characteristics, treatments, and outcomes were collected. Associations between exposure to STP, FFA, and CBD and SE incidence, duration, refractoriness, and pediatric intensive care unit (PICU) admission were assessed using regression models adjusted for age and follow-up time. RESULTS: Sixty-one patients (median age 13 years) experienced 1033 SE episodes, predominantly convulsive (89.9%). Benzodiazepines were highly effective as first-line therapy, achieving seizure termination in 95.8% of treated episodes. In regression analyses, FFA was associated with reduced SE incidence (IRR 0.19, p < 0.001), while STP showed a non-significant reduction (IRR 0.75, p = 0.286). A cumulative effect was observed, with each additional ASM further lowering SE incidence (IRR 0.63 per drug, p = 0.030). Stiripentol was associated with shorter SE duration (β -5.0 min, p = 0.003), whereas CBD showed a non-significant effect (β -2.7 min, p = 0.506). SE duration decreased with each additional ASM (β -3.7 min per drug, p = 0.038). CONCLUSION: In this large real-world cohort, early benzodiazepine administration was highly effective for SE management. Exposure to novel ASMs was associated with a reduced SE burden, supporting optimized long-term therapy to reduce SE frequency and severity in DS.