Authors :
Presenting Author: Ana Fornari Caprara, MD – Cooper Univeristy Hospital
Jamir Pitton Rissardo, MD – Cooper Univeristy Hospital
Evren Burakgazi-Dalkilic, MD – Cooper Univeristy Hospital
Rationale:
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by treatment-resistant seizures and high morbidity. Despite the emergence of targeted therapies, first-line management remains challenging. Fenfluramine (FFA), a serotonergic agent with anti-seizure properties, has shown promise as an add-on therapy. This systematic review and meta-analysis aimed to evaluate the efficacy of FFA compared to placebo as a first-line add-on treatment in reducing seizure burden among patients with DS.Methods:
A systematic review was conducted according to PRISMA guidelines. Databases were searched for randomized controlled trials (RCTs) assessing FFA versus placebo in DS patients. Studies were eligible if they assessed FFA as a first-line add-on therapy and reported seizure outcomes, including median convulsive seizure frequency (MCSF) and ≥50% and ≥75% responder rates. Risk differences (RD) with 95% confidence intervals (CIs) were extracted or calculated for seizure reduction endpoints. Random-effects meta-analyses were performed using inverse variance methods.Results:
Three treatment arms across two high-quality, double-blind RCTs (PMIDs: 31862249, 31790543) were included, involving a total of 247 patients. FFA doses ranged from 0.2 to 0.7 mg/kg/day. Compared to placebo, the pooled RD for ≥50% reduction in MCSF was –0.18 (95% CI: –0.278 to –0.082), indicating a statistically significant benefit. The RD for ≥75% seizure reduction was –0.14 (95% CI: –0.222 to –0.059), also favoring FFA. The RD for change in median convulsive seizure frequency showed consistent trends but with wider confidence intervals (e.g., RD for 0.7 mg/kg/day: –55.7; 95% CI: –105.6 to 217.0), likely due to heterogeneity in baseline seizure rates. Subgroup analysis by dose suggested greater efficacy at 0.4–0.7 mg/kg/day compared to 0.2 mg/kg/day.Conclusions:
This meta-analysis supports the efficacy of fenfluramine as a first-line add-on therapy in reducing seizure frequency in patients with Dravet syndrome. Clinically meaningful improvements were observed in both ≥50% and ≥75% responder rates. The benefit appeared dose-dependent, with higher doses yielding greater seizure control. These findings support consideration of FFA in early treatment algorithms for DS, although further studies are needed to confirm long-term effectiveness and safety in broader clinical practice.
Funding:
None to disclose.