PDF(Pubmed)
Abstract：
UNASSIGNED: Several clinical trials have suggested that fenfluramine (FFA) is effective for the treatment of epilepsy in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). However, the exploration of its optimal target dose is ongoing. This study aimed to summarize the best evidence to inform this clinical issue.
UNASSIGNED: We searched PubMed, Embase (via Ovid), and Web of Science for relevant literature published before December 1st, 2023. Randomized, double-blind, placebo-controlled studies that evaluated the efficacy, safety, and tolerability of FFA in DS and LGS were identified and meta-analysis was performed according to doses. The study was registered with PROSPERO (CRD42023392454).
UNASSIGNED: Six hundred and twelve patients from four randomized controlled trials were enrolled. The results demonstrated that FFA at 0.2, 0.4, or 0.7 mg/kg/d showed significantly greater efficacy compared to placebo in terms of at least 50% reduction (p < 0.001, p < 0.001, p < 0.001) and at least 75% reduction (p < 0.001, p = 0.007, p < 0.001) in monthly seizure frequency from baseline. Moreover, significantly more patients receiving FFA than placebo were rated as much improved or very much improved in CGI-I by both caregivers/parents and investigators (p < 0.001). The most common treatment-emergent adverse events were decreased appetite, diarrhea, fatigue, and weight loss, with no valvular heart disease or pulmonary hypertension observed in any participant. For dose comparison, 0.7 mg/kg/d group presented higher efficacy on at least 75% reduction in seizure (p = 0.006) but not on at least 50% reduction. Weight loss (p = 0.002), decreased appetite (p = 0.04), and all-cause withdrawal (p = 0.036) were more common in 0.7 mg/kg/d group than 0.2 mg/kg/d. There was no statistical difference in other safety parameters between these two groups.
UNASSIGNED: The higher range of the licensed dose achieves the optimal balance between efficacy, safety, and tolerability in patients with DS and LGS.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392454.
UNASSIGNED: We searched PubMed, Embase (via Ovid), and Web of Science for relevant literature published before December 1st, 2023. Randomized, double-blind, placebo-controlled studies that evaluated the efficacy, safety, and tolerability of FFA in DS and LGS were identified and meta-analysis was performed according to doses. The study was registered with PROSPERO (CRD42023392454).
UNASSIGNED: Six hundred and twelve patients from four randomized controlled trials were enrolled. The results demonstrated that FFA at 0.2, 0.4, or 0.7 mg/kg/d showed significantly greater efficacy compared to placebo in terms of at least 50% reduction (p < 0.001, p < 0.001, p < 0.001) and at least 75% reduction (p < 0.001, p = 0.007, p < 0.001) in monthly seizure frequency from baseline. Moreover, significantly more patients receiving FFA than placebo were rated as much improved or very much improved in CGI-I by both caregivers/parents and investigators (p < 0.001). The most common treatment-emergent adverse events were decreased appetite, diarrhea, fatigue, and weight loss, with no valvular heart disease or pulmonary hypertension observed in any participant. For dose comparison, 0.7 mg/kg/d group presented higher efficacy on at least 75% reduction in seizure (p = 0.006) but not on at least 50% reduction. Weight loss (p = 0.002), decreased appetite (p = 0.04), and all-cause withdrawal (p = 0.036) were more common in 0.7 mg/kg/d group than 0.2 mg/kg/d. There was no statistical difference in other safety parameters between these two groups.
UNASSIGNED: The higher range of the licensed dose achieves the optimal balance between efficacy, safety, and tolerability in patients with DS and LGS.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392454.
摘要：
■一些临床试验表明，芬氟拉明（FFA）可有效治疗Dravet综合征（DS）和Lennox-Gastaut综合征（LGS）的癫痫。然而,其最佳目标剂量的探索正在进行中。本研究旨在总结最佳证据，以告知这一临床问题。
■我们搜索了PubMed，Embase（通过Ovid），和WebofScience在12月1日之前发表的相关文献，2023年。随机化,双盲,评估疗效的安慰剂对照研究，安全,确定DS和LGS中FFA的耐受性，并根据剂量进行荟萃分析。该研究在PROSPERO（CRD42023392454）注册。
■纳入了来自四项随机对照试验的六百十二名患者。结果表明，与安慰剂相比，0.2、0.4或0.7mg/kg/d的FFA在从基线开始的每月发作频率中至少减少50％（p<0.001，p<0.001，p<0.001）和至少75％减少（p<0.001，p=0.007，p<0.001）方面显示出明显更大的功效。此外，护理人员/父母和研究者将接受FFA的患者的CGI-I评分为显著改善或非常改善(p<0.001).最常见的治疗引起的不良事件是食欲下降，腹泻,疲劳,和减肥,在任何参与者中均未观察到瓣膜性心脏病或肺动脉高压。对于剂量比较，0.7mg/kg/d组在癫痫发作减少至少75％（p=0.006）但没有减少至少50％时表现出更高的疗效。体重减轻（p=0.002），食欲下降（p=0.04），全因戒断(p=0.036)在0.7mg/kg/d组比0.2mg/kg/d组更常见。两组之间的其他安全性参数没有统计学差异。
■许可剂量的较高范围实现了功效之间的最佳平衡，安全,DS和LGS患者的耐受性。
■https://www.crd.约克。AC.英国/PROSPERO/,标识符CRD42023392454。
■我们搜索了PubMed，Embase（通过Ovid），和WebofScience在12月1日之前发表的相关文献，2023年。随机化,双盲,评估疗效的安慰剂对照研究，安全,确定DS和LGS中FFA的耐受性，并根据剂量进行荟萃分析。该研究在PROSPERO（CRD42023392454）注册。
■纳入了来自四项随机对照试验的六百十二名患者。结果表明，与安慰剂相比，0.2、0.4或0.7mg/kg/d的FFA在从基线开始的每月发作频率中至少减少50％（p<0.001，p<0.001，p<0.001）和至少75％减少（p<0.001，p=0.007，p<0.001）方面显示出明显更大的功效。此外，护理人员/父母和研究者将接受FFA的患者的CGI-I评分为显著改善或非常改善(p<0.001).最常见的治疗引起的不良事件是食欲下降，腹泻,疲劳,和减肥,在任何参与者中均未观察到瓣膜性心脏病或肺动脉高压。对于剂量比较，0.7mg/kg/d组在癫痫发作减少至少75％（p=0.006）但没有减少至少50％时表现出更高的疗效。体重减轻（p=0.002），食欲下降（p=0.04），全因戒断(p=0.036)在0.7mg/kg/d组比0.2mg/kg/d组更常见。两组之间的其他安全性参数没有统计学差异。
■许可剂量的较高范围实现了功效之间的最佳平衡，安全,DS和LGS患者的耐受性。
■https://www.crd.约克。AC.英国/PROSPERO/,标识符CRD42023392454。
