Fenfluramine below the age of 2 years in Dravet syndrome: What about safety and efficacy?

Pietrafusa, Nicola; Trivisano, Marina; Casellato, Susanna; Correale, Cinzia; Cappelletti, Simona; De Liso, Paola; Onida, Ilaria; Sotgiu, Stefano; Butera, Ambra; Specchio, Nicola; Vigevano, Federico

doi:10.1111/epi.17854

Cited by 3 publications

(1 citation statement)

References 20 publications

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“…Studies show that fenfluramine is a highly effective drug in reducing epileptic seizures and is safe for use even in the youngest patients [ 15 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

How Has the Treatment of Polish Children with Dravet Syndrome Changed? Future Perspectives

Zielińska,

Skarżyńska,

Górka-Skoczylas

et al. 2024

Biomedicines

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Background: This report focuses on the treatment histories of 21 patients diagnosed with Dravet syndrome (DRVT) under the care of the Mother and Child Institute in Warsaw. This paper aims to present typical treatment schemes for patients with drug-resistant epilepsy, as well as to highlight the influence of genetic diagnosis on pharmacotherapeutic management and to present an economic analysis of hospitalization costs. This paper will also summarize the effectiveness of the latest drugs used in DRVT. Methods: Clinical data were collected retrospectively from available medical records. The effectiveness of anticonvulsant treatment was assessed based on epileptic seizure diaries and observations by caregivers and pediatric neurologists. Results: The study group (n = 21) consisted of patients aged 3–26 years. Orphan drugs dedicated to Dravet syndrome were introduced in all patients due to the genetic diagnosis, which significantly improved the patients’ clinical conditions. The breakthrough drugs were stiripentol (in 16/21) and fenfluramine (in 3/21). Conclusions: In recent years, molecular genetics has rapidly developed in Poland, along with a steady increase in knowledge of Dravet syndrome among the medical profession. Early and precise diagnosis provides the opportunity to target treatment with drugs dedicated to Dravet syndrome with high efficacy.

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“…Studies show that fenfluramine is a highly effective drug in reducing epileptic seizures and is safe for use even in the youngest patients [ 15 , 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

How Has the Treatment of Polish Children with Dravet Syndrome Changed? Future Perspectives

Zielińska,

Skarżyńska,

Górka-Skoczylas

et al. 2024

Biomedicines

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Fenfluramine treatment in pediatric patients with Dravet syndrome reduces seizure burden and overall healthcare costs: A retrospective and observational real‐world study

Gjerulfsen,

Nikanorova,

Olofsson

et al. 2024

Epilepsia Open

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ObjectivesDravet syndrome is a developmental and epileptic encephalopathy characterized by early onset epilepsy with multiple seizure types often intractable to treatment. Randomized clinical trials have demonstrated how treatment with fenfluramine significantly reduces seizure frequency in patients with Dravet syndrome. The study aims to (1) describe the efficacy and tolerability of fenfluramine in a Danish cohort of patients with Dravet syndrome; and (2) evaluate whether treatment with fenfluramine reduces epilepsy‐related hospital contacts administrated by pediatricians or epilepsy‐trained nurses.MethodsA retrospective registry‐based cohort study at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark, enrolled 30 pediatric patients with Dravet syndrome treated with fenfluramine between 2017 and 2023.ResultsThirty patients with Dravet syndrome (aged 3–21 years, 12 females) with a verified pathogenic SCN1A variant were included. They were treated with fenfluramine at a mean duration of 29 months with a mean maintenance dose of 0.5 mg/kg/day. The number of patient‐years on treatment was 75 years. At last follow‐up, 6 patients had discontinued treatment due to lack of efficacy or adverse effects. In the remaining 24 patients, generalized tonic–clonic seizures were reduced by ≥30% in 83%, by ≥50% in 67%, and by 100% in 25%. Additionally, 71% of the patients were reduced in concomitant anti‐seizure medication, and 75% experienced a reduction (mean reduction at 52%, range 11%–94%) in epilepsy‐related hospital contacts from baseline to the end of the treatment period.SignificanceTreatment with fenfluramine effectively reduced seizure frequency and concomitant antiseizure medication in patients with Dravet syndrome. Furthermore, a decrease in epilepsy‐related contacts by 80% was observed over 6 years of treatment, which may indicate cost‐effective benefits.Plain Language SummaryPatients with Dravet syndrome suffer from severe epileptic seizures that are difficult to treat with medication. Earlier, treatment with fenfluramine (an anti‐seizure medication) has been documented to decrease the total number of seizures in patients with Dravet syndrome. This publication summarizes the experiences with fenfluramine in children with Dravet syndrome at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark. Our publication also illustrates that treatment with fenfluramine may reduce the patients' number of yearly contacts with doctors and nurses specialized in epilepsy treatment, which may indicate cost‐effectiveness.

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Prevention of Drug Resistant Epilepsy and Developmental Epileptic Encephalopathy: Preventative Vigabatrin Treatment in Tuberous Sclerosis Complex and the Case for Fenfluramine Treatment of Children with Newly Diagnosed Dravet Syndrome

Pong,

Klein

2024

OBM Genet

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Tuberous sclerosis complex (TSC) is caused by mutations of hamartin (TSC1) or tuberin (TSC2) resulting in disinhibition of the mTOR pathway of cellular proliferation and differentiation and severe neurocognitive impairment, intractable epilepsy and tumors. Epilepsy develops in ~90% folllowed by drug-resistant epilepsy (DRE). Recently, prevention of DRE and developmental encephalopathy was shown to be possible in TSC using early administration of vigabatrin. For the first time, medical treatment successfully prevented epilepsy and reduced neurocognitive and behavioural co-morbidities. The crucial difference between the preventive and standard treatment groups was the timing of treatment initiation, not the type of the intervention. This paradigm can be extended to patients with other genetic or acquired conditions, including Dravet Syndrome (DS), a severe developmental epileptic encephalopathy (DEE) with DRE and high mortality, due to a de novo mutation of the gene SCN1A which codes for the sodium channel protein <em>a</em> subunit Na<sub>v</sub>1.1. Infants usually develop normally until their first seizure, commonly between 2-15 months. This is followed by DRE and developmental regression. Randomized controlled trials (RCTs) of adjunctive fenfluramine treatment in DS reduced median convulsive seizure frequency by 55.7% over placebo at 0.7 mg/kg/day. 50% of children had 75% seizure frequency reduction, 8% had convulsive seizure freedom versus 0% with placebo, and 18% had only one convulsive seizure versus 0% with placebo. Other pivotal studies showed similar results and efficacy was sustained in for <3 years. Fenfluramine is now a first-line therapy for DS. Given the existence of a remarkably effective treatment fenfluramine for Dravet, preventive therapy presents itself as a natural extension for its application. We hypothesize that not only may seizure outcomes such as time to second seizure and evolution to DRE be positively impacted, but moreover, protective effects on mortality and cognitive outcomes may also be seen.

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Fenfluramine below the age of 2 years in Dravet syndrome: What about safety and efficacy?

Cited by 3 publications

References 20 publications

How Has the Treatment of Polish Children with Dravet Syndrome Changed? Future Perspectives

How Has the Treatment of Polish Children with Dravet Syndrome Changed? Future Perspectives

Fenfluramine treatment in pediatric patients with Dravet syndrome reduces seizure burden and overall healthcare costs: A retrospective and observational real‐world study

Prevention of Drug Resistant Epilepsy and Developmental Epileptic Encephalopathy: Preventative Vigabatrin Treatment in Tuberous Sclerosis Complex and the Case for Fenfluramine Treatment of Children with Newly Diagnosed Dravet Syndrome

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