Dravet syndrome in children—A population-based study

Bjurulf, Björn; Reilly, Colin; Sigurdsson, Gudmundur Vignir; Thunström, Sofia; Kolbjer, Sintia; Hallböök, Tove

doi:10.1016/j.eplepsyres.2022.106922

Cited by 18 publications

(28 citation statements)

References 44 publications

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“…Mortality was significantly higher in DS patients than in age‐ and sex‐matched controls (people without DEEs) identified from the same healthcare insurance claims database over an equal observation time (11.9% vs 1.2%, P < 0.001) 39 . The most common reasons for death across all studies were SUDEP followed by SE 14,16,31,32,40–42 …”

Section: Resultsmentioning

confidence: 94%

“…The incidence ranged from 1:15 400 to 1:40 900 (1:15 400 to 1:40 000 in studies exclusively in children, 30,31,33–36 and 1:40 900 in one study that included both children and adults 32 ). The prevalence ranged from 1.5 per 100 000 to 6.5 per 100 000 31,34,37–39 . The risk of bias was low in seven studies and moderate in three studies (Table S6).…”

Section: Resultsmentioning

confidence: 99%

“…Overall, 10 studies were identified that reported on incidence (seven studies [30][31][32][33][34][35][36] ) and/or prevalence (five studies 31,34,[37][38][39] ) (Table S2). The studies differed in their publication year (1990-2022 for incidence and 2015-2022 for prevalence), country (2 from the US, 33,35 and 5 from across Europe for incidence [30][31][32]34,36 and 1 from the US, 37 and 4 from across Europe for prevalence 31,34,38,39 ), duration of follow-up, and patient population including the diagnostic criteria, average age and population size.…”

Section: Epidemiology: Incidence Prevalence and Mortalitymentioning

confidence: 99%

“…The prevalence ranged from 1.5 per 100 000 to 6.5 per 100 000. 31,34,[37][38][39] The risk of bias was low in seven studies and moderate in three studies (Table S6).…”

Section: Epidemiology: Incidence Prevalence and Mortalitymentioning

confidence: 99%

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Dravet syndrome: A systematic literature review of the illness burden

Strzelczyk,

Lagae,

Wilmshurst

et al. 2023

Epilepsia Open

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ObjectiveWe performed a systematic literature review and narrative synthesis according to a pre‐registered protocol (Prospero: CRD42022376561) to identify the evidence associated with the burden of illness in Dravet syndrome (DS), a developmental and epileptic encephalopathy characterised by drug‐resistant epilepsy with neurocognitive and neurobehavioural impairment.MethodsWe searched MEDLINE, Embase and APA PsychInfo, Cochrane's database of systematic reviews, and Epistemonikos from inception to June 2022. Non‐interventional studies reporting on epidemiology (incidence, prevalence and mortality), patient and caregiver health‐related quality of life (HRQoL), direct and indirect costs and healthcare resource utilisation were eligible. Two reviewers independently carried out the screening. Pre‐specified data were extracted and a narrative synthesis was conducted.ResultsOverall, 49 studies met the inclusion criteria. The incidence varied from 1:15,400–1:40,900, and the prevalence varied from 1.5 per 100,000 to 6.5 per 100,000. Mortality was reported in 3.7–20.8% of DS patients, most commonly due to sudden unexpected death in epilepsy and status epilepticus. Patient HRQoL, assessed by caregivers, was lower than in non‐DS epilepsy patients; mean scores (0 [worst] to 100/1 [best]) were 62.1 for the Kiddy KINDL/ Kid‐KINDL, 46.5–54.7 for the PedsQL and 0.42 for the EQ‐5D‐5L. Caregivers, especially mothers, were severely affected, with impacts on their time, energy, sleep, career, and finances, while siblings were also affected. Symptoms of depression were reported in 47% to 70% of caregivers. Mean total direct costs were high across all studies, ranging from $11,048 to $77,914 per patient per year (PPPY), with inpatient admissions being a key cost driver across most studies. Mean costs related to lost productivity were only reported in three publications, ranging from approximately $19,000 to $20,000 PPPY ($17,596 for mothers versus $1,564 for fathers). High seizure burden was associated with higher resource utilisation, costs and poorer HRQoL.SignificanceThe burden of DS on patients, caregivers, the healthcare system and society is profound, reflecting the severe nature of the syndrome. Future studies will be able to assess the impact that newly approved therapies have on reducing the burden of DS.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Epidemiology: Incidence Prevalence and Mortalitymentioning

confidence: 99%

“…The prevalence ranged from 1.5 per 100 000 to 6.5 per 100 000. 31,34,[37][38][39] The risk of bias was low in seven studies and moderate in three studies (Table S6).…”

Section: Epidemiology: Incidence Prevalence and Mortalitymentioning

confidence: 99%

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Dravet syndrome: A systematic literature review of the illness burden

Strzelczyk,

Lagae,

Wilmshurst

et al. 2023

Epilepsia Open

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“…Dravet syndrome progression is divided into three stages: heating, deterioration, and stability ( Wheless et al, 2020 ). The overall incidence of DS is approximately 1/40,900–1/22,000, accounting for approximately 29.5% of various types of myoclonic epilepsy in children ( Brunklaus et al, 2012 ; Bayat et al, 2015 ; Wu et al, 2015 ; Bjurulf et al, 2022 ). Studies have found that DS is related to mutations in the SCN1A gene, which encodes the NaV1.1 channel, and more than 85% of patients have mutations in this gene ( Claes et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A systematic review and network meta-analysis

Zhang

et al. 2022

Front. Pharmacol.

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Purpose: Recently, the U.S. Food and Drug Administration (FDA) approved stiripentol, cannabidiol, and fenfluramine to treat patients with Dravet syndrome (DS). Moreover, soticlestat was determined as a promising new drug for the treatment of DS as it has good efficacy and safety. However, the efficacy and safety of these drugs have not yet been evaluated in “head-to-head” trials. This study aimed to compare and evaluate the efficacy and safety of these adjunctive antiseizure medications in the treatment of DS.Methods: We searched in PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) and open-label extension (OLE) studies in patients with DS. We performed a random-effect meta-analysis of OLE studies and a network meta-analysis for RCTs to evaluate the efficacy and safety of antiseizure medications in the treatment of DS. Primary efficacy outcomes were defined as a ≥50% reduction in seizure frequency compared with baseline. Furthermore, safety evaluation indicators were defined as the incidence of adverse events (AEs) and serious adverse events (SAEs) during treatment. Relative ranking was assessed using the surface under the cumulative ranking curve (SUCRA) probabilities.Results: Seven RCTs involving four antiseizure medications (stiripentol, cannabidiol, fenfluramine, and soticlestat) and a total of 634 patients were included in the analysis. According to the SUCRA results, all four drugs significantly reduced the frequency of seizures compared with the placebo. Soticlestat was the most likely to reduce seizure frequency by ≥50% compared to the baseline [risk ratio (RR): 19.32; 95% confidence interval (CI): 1.20–311.40], followed by stiripentol and fenfluramine. Stiripentol was ranked highest for the near percentage reduction in the seizure rate from baseline [RR: 12.33; 95% CI: 1.71–89.17] and the occurrence of any treatment-emergent adverse events [RR: 3.73; 95% CI: 1.65–8.43] and serious adverse events [RR: 4.76; 95% CI: 0.61–37.28]. A total of ten OLE studies containing 1,121 patients were included in our study. According to the results of the meta-analysis, the order of probability of reducing seizure frequency by ≥50% was fenfluramine (0.715, 95% CI: 0.621–0.808), stiripentol (0.604, 95% CI: 0.502–0.706), cannabidiol (0.448, 95% CI: 0.403–0.493). And the probability of occurrence of AEs is ranked as fenfluramine(0.832, 95% CI: 0.795–0.869), cannabidiol (0.825, 95% CI:0.701–0.950), stiripentol (0.823, 95% CI: 0.707–0.938), soticlestat (0.688, 95% CI: 0.413–0.890).Conclusion: According to the results of indirect comparison of efficacy and safety, cannabidiol is slightly inferior to the other three antiseizure medications in terms of efficacy and safety. Soticlestat, fenfluramine, and stripentol may have little difference in efficacy, but soticlestat and fenfluramine are safer. Soticlestat is probably the best adjunctive antiseizure medication, followed by fenfluramine. This conclusion is consistent with the comparison of long-term efficacy and safety.

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