Premium
Efficacy and safety of fenfluramine in patients with Dravet syndrome: A meta‐analysis
Author(s) -
Zhang Lanlan,
Li Wei,
Wang Chengzhong
Publication year - 2021
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.13387
Subject(s) - dravet syndrome , medicine , fenfluramine , placebo , meta analysis , cochrane library , randomized controlled trial , adverse effect , relative risk , epilepsy syndromes , pediatrics , epilepsy , anesthesia , confidence interval , psychiatry , receptor , alternative medicine , pathology , serotonin
Background Dravet syndrome (DS) is a severe, drug‐resistant, developmental epileptic encephalopathy. Despite multiple anti‐epileptic drug regimens, the syndrome remains poorly controlled and nearly half of patients still experience at least four tonic‐clonic seizure per month. Recently, several clinical trials demonstrated that fenfluramine may provide a significant reduction in convulsive seizure frequency in the treatment of Dravet syndrome. Methods A computerized literature search of Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar was performed from inception until December 31, 2019. We included randomized placebo‐controlled trials for the treatment of Dravet syndrome. We calculated the risk ratio (RR) of ≥50% and 100% reduction seizure frequency from baseline, along with the treatment‐related withdrawals and serious adverse events, using the fixed‐effect model. Quality assessment of included studies was performed with the Cochrane Collaboration's tool. Key Results Two trials with a total of 206 patients were included. The pooled RR of 5.49 (95% CI 3.13‐9.65) showed that a significantly greater proportion in the fenfluramine group achieved ≥50% reduction in monthly convulsive seizure frequency (MCSF). As for the complete seizure free rate, the pooled RR of 5.75 (95% CI 1.03‐32.07) also demonstrated the favorable efficacy of fenfluramine, even though the difference was not statistically significant ( p = 0.046). However, a significantly greater proportion of patients in the fenfluramine group experienced no more than one seizure during the treatment period (RR 13.82, 95% CI 2.68‐71.27, p = 0.002). There were no significant differences in withdrawals and serious adverse events between the two treatment groups. No valvular heart disease or pulmonary arterial hypertension was observed in participants. The most common adverse events reported by included trials were diarrhea, fatigue, lethargy, nasopharyngitis, pyrexia, seizure, decreased appetite, and weight loss. Conclusions Fenfluramine is an effective antiepileptic drug for pediatric patients with Dravet syndrome, demonstrating clinically meaningful reduction in convulsive frequency, and generally could be well tolerated.