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Войти в исследования Seizure · 2026
Fenfluramine in developmental and epileptic encephalopathies: An age- and syndrome-stratified systematic review and meta-analysis.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод в очереди
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de Oliveira Helen Michaela, Fonseca Pandora Eloa Oliveira, de Paula Guilherme Oliveira, Blaskoski Amanda Pinzon, da Costa Pablo Ramon Fruett
Аннотация
PURPOSE: Developmental and epileptic encephalopathies (DEEs) are heterogeneous developmental encephalopathies in which ongoing epileptic activity contributes to worsening of pre-existing cognitive, behavioral, and motor impairment. Fenfluramine evidence is strongest in Dravet syndrome (DS), but limited in Lennox-Gastaut syndrome (LGS), other DEEs, and adults. We evaluated efficacy by syndrome and age, considering follow-up for durability.
METHODS: We conducted a systematic review and meta-analysis (PROSPERO CRD420251161054). PubMed, Embase, and CENTRAL were searched from inception to 15 September 2025. Eligible studies enrolled individuals with DEE treated with fenfluramine. Subgroup analy RESULTS: Twenty studies (4 randomized, 16 observational) comprising 1387 patients met criteria. Pooled estimates were 16.7% (95% CI 10.3-25.8) for minimal/no benefit, 64.8% (56.1-72.7) for ≥50% response, 41.6% (32.1-51.8) for ≥70% reduction, and 11.4% (7.2-17.6) for seizure freedom. Syndrome-stratified analyses strengthened the signal of differential efficacy: response was consistently attenuated in LGS compared with DS in ≥50% and ≥70% thresholds, with significant subgroup interactions, supporting a credible between-syndrome difference. Other DEEs showed higher point estimates (e.g.: ≥50%=100%; ≥70%=77.8%) but were informed by few studies. Adults had higher seizure-freedom estimates (38.2%vs 11.3% mixed and 8.2% pediatric); this signal is clinically relevant but should be interpreted in light of DS predominance and the age-related evolution of seizure burden in DS. Follow-up was heterogeneous; long-term data, mainly from DS cohorts, did not suggest systematic loss of efficacy.
CONCLUSION: Fenfluramine provides clinically meaningful seizure reduction across DEEs, with differential efficacy by syndrome and encouraging long-term durability, particularly in DS.
METHODS: We conducted a systematic review and meta-analysis (PROSPERO CRD420251161054). PubMed, Embase, and CENTRAL were searched from inception to 15 September 2025. Eligible studies enrolled individuals with DEE treated with fenfluramine. Subgroup analy RESULTS: Twenty studies (4 randomized, 16 observational) comprising 1387 patients met criteria. Pooled estimates were 16.7% (95% CI 10.3-25.8) for minimal/no benefit, 64.8% (56.1-72.7) for ≥50% response, 41.6% (32.1-51.8) for ≥70% reduction, and 11.4% (7.2-17.6) for seizure freedom. Syndrome-stratified analyses strengthened the signal of differential efficacy: response was consistently attenuated in LGS compared with DS in ≥50% and ≥70% thresholds, with significant subgroup interactions, supporting a credible between-syndrome difference. Other DEEs showed higher point estimates (e.g.: ≥50%=100%; ≥70%=77.8%) but were informed by few studies. Adults had higher seizure-freedom estimates (38.2%vs 11.3% mixed and 8.2% pediatric); this signal is clinically relevant but should be interpreted in light of DS predominance and the age-related evolution of seizure burden in DS. Follow-up was heterogeneous; long-term data, mainly from DS cohorts, did not suggest systematic loss of efficacy.
CONCLUSION: Fenfluramine provides clinically meaningful seizure reduction across DEEs, with differential efficacy by syndrome and encouraging long-term durability, particularly in DS.