Seizure management and prescription patterns of anticonvulsants in Dravet syndrome: A multicenter cohort study from Germany and review of literature

Schubert‐Bast, Susanne; Wolff, Markus; Wiemer‐Kruel, Adelheid; Spiczak, Sarah von; Trollmann, Regina; Reif, Philipp S.; Pritchard, Clive; Polster, Tilman; Neubauer, Bernd A.; Mayer, Thomas; Macdonald, Daniel; Kurlemann, Gerhard; Kluger, Gerhard; Klein, Karl Martin; Kieslich, Matthias; Kay, Lara; Kalski, Malin; Irwin, J. David; Herting, A.; Carroll, J.; Bettendorf, U; Bast, Thomas; Rosenow, Felix; Strzelczyk, Adam

doi:10.1016/j.yebeh.2019.06.021

Cited by 28 publications

(30 citation statements)

References 32 publications

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“…Some support for this has been found in our study's high patient spend in the DS group on specialist equipment, as well as high use of rescue medication. 29 Furthermore, two pediatric DRE patients were reported to have spent the entire 3-month duration of the study in hospital, which caused a significant increase in the direct costs of this patient group and served to illustrate the heterogeneity in this group.…”

Section: T a B L Ementioning

confidence: 99%

A multicenter, matched case‐control analysis comparing burden‐of‐illness in Dravet syndrome to refractory epilepsy and seizure remission in patients and caregivers in Germany

et al. 2019

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Objective To compare direct and indirect costs and quality of life (QoL) of pediatric and adult patients with Dravet syndrome (DS), with drug‐resistant epilepsy (DRE) and in seizure remission (SR), and their caregivers, in Germany. Methods Questionnaire responses from 93 DS patients and their caregivers were matched by age and gender with responses from 93 DRE and 93 SR patients collected in independent studies, and were compared across main components of QoL, direct costs (patient visits, medication use, care level, medical equipment, and ancillary treatments), and indirect costs (quitting job, reduced working hours, missed days). Results Mean total direct costs were highest for DS patients (€4864 [median €3564] vs €3049 [median €1506] for DRE [excluding outliers], P = 0.01; and €1007 [median €311], P < 0.001 for SR). Total lost productivity over 3 months was highest among caregivers of pediatric DS (€4757, median €2841), compared with those of DRE (€1541, P < 0.001; median €0) and SR patients (€891, P < 0.001; median €0). The proportions of caregivers in employment were similar across groups (62% DS, 63% DRE, and 63% SR) but DS caregivers were more likely to experience changes to their working situation, such as quitting their job (40% DS vs 16% DRE and 9% SR, P < 0.001 in both comparisons). KINDL scores were significantly lower for DS patients (62 vs 74 and 72, P < 0.001 in both comparisons), and lower than for the average German population (77). Pediatric caregiver EQ‐5D scores across all cohorts were comparable with population norms, but more DS caregivers experienced moderate to severe depressive symptoms (24% vs 11% and 5%). Mean Beck Depression Inventory (BDI‐II) score was significantly higher in DS caregivers than either of the other groups (P < 0.001). Significance This first comparative study of Dravet syndrome to difficult‐to‐treat epilepsy and to epilepsy patients in seizure remission emphasizes the excess burden of DS in components of QoL and direct costs. The caregivers of DS patients have a greater impairment of their working lives (indirect costs) and increased depression symptoms.

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Section: T a B L Ementioning

confidence: 99%

A multicenter, matched case‐control analysis comparing burden‐of‐illness in Dravet syndrome to refractory epilepsy and seizure remission in patients and caregivers in Germany

et al. 2019

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“…No significant impact on the pharmacokinetics of clobazam, valproate and cannabidiol has been observed with fenfluramine [107,108]. A combination of stiripentol with valproate + clobazam led to an increase in the peak plasma levels and systematic exposure of fenfluramine, requiring a reduction in the dose of fenfluramine (to a maximum dose of 0.4 mg/kg/day) when administered in combination with the stiripentol regimen, although this is more relevant to the treatment of DS [107,109].…”

Section: Other Considerations: Drug-drug Interactionsmentioning

confidence: 99%

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies

Strzelczyk

Schubert‐Bast

2021

CNS Drugs

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Lennox-Gastaut syndrome (LGS), a childhood-onset severe developmental and epileptic encephalopathy (DEE), is an entity that encompasses a heterogenous group of aetiologies, with no single genetic cause. It is characterised by multiple seizure types, an abnormal EEG with generalised slow spike and wave discharges and cognitive impairment, associated with high morbidity and profound effects on the quality of life of patients and their families. Drug-refractory seizures are a hallmark and treatment is further complicated by its multiple morbidities, which evolve over the patient’s lifetime. This review provides a comprehensive overview of the current and future options for the treatment of seizures associated with LGS. Six treatments are specifically indicated as adjunct therapies for the treatment of seizures associated with LGS in the US: lamotrigine, clobazam, rufinamide, topiramate, felbamate and most recently cannabidiol. These therapies have demonstrated reductions in drop seizures in 15%–68% of patients across trials, with responder rates (≥ 50% reduction in drop seizures) of 37%–78%. Valproate is still the preferred first-line treatment, generally in combination with lamotrigine or clobazam. Other treatments frequently used off-label include the broad spectrum anti-epileptic drugs (AED) levetiracetam, zonisamide and perampanel, while recent evidence from observational studies has indicated that a newer AED, the levetiracetam analogue brivaracetam, may be effective and well tolerated in LGS patients. Other treatments in clinical development include fenfluramine in late phase III, perampanel, soticlestat–OV953/TAK-953, carisbamate and ganaxolone. Non-pharmacologic interventions include the ketogenic diet, vagus nerve stimulation and surgical interventions; these are also expanding, with the potential for less invasive techniques for corpus callosotomy that have promise for reducing complications. However, despite these advancements, patients continue to experience a significant burden. Because LGS is not a single entity, tailoring of treatment is needed as opposed to a ‘one size fits all’ approach. Further research is needed into the underlying aetiologies and pathophysiology of LGS, together with advancements in treatments that encompass the spectrum of seizures associated with this complex syndrome.

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“…Die Untersuchung der Lebensqualität ergab einen mittleren EQ-5D-5L-Index-Wert von 0,60 (Standardabweichung ± 0,26) für Betroffene älter als 2 Jahre und liegt damit unterhalb des mittleren deutschen Indexwertes von 0,88 [12]. Zwi- [11,13] und denen einer anderen in 2017 prospektiv durchgeführten, multizentrischen Querschnittsstudie mit 93 befragten Eltern in Deutschland, die der vorliegenden Studie hinsichtlich demografischer und klinischer Basisdaten ähnelt, verglichen [9,14,15]. Die Diagnose eines DS erfolgt klinisch und wird durch den Nachweis einer Mutation im SCN1A-Gen unterstützt; die Zeit bis zur korrekten Diagnose eines DS hat sich in den letzten Jahren in Deutschland signifikant verkürzt, wie in dieser Untersuchung und der 2017 Kohortenstudie gezeigt werden konnte [14].…”

Section: Lebensqualitätunclassified

“…48,5 %) häufiger in der deutschen Kohorte eingenommen wurde. Die Ergebnisse decken sich mit den Ergebnissen der deutschen Querschnittsstudie aus 2017, in der diese 4 Medikamente (66,0, 35,0, 41,0 und 24,0 %) und Kaliumbromid (44,0 %) ebenfalls die am häufigsten eingenommenen AED waren [9,15]. Der Einsatz von Kaliumbromid erfolgte in der deutschen Kohorte vorwiegend in der Altersgruppe der Vorschulkinder (62,5 %) und bei den Grundschulkindern (54,2 %, .…”

Section: Einfluss Auf Familienunclassified

Klinische Charakteristika und Lebensqualität beim Dravet-Syndrom: Ergebnisse der deutschen Kohorte des „Dravet syndrome caregiver survey“ (DISCUSS)

Strzelczyk

Lagae

Kurlemann

et al. 2021

Monatsschr Kinderheilkd

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Zusammenfassung Hintergrund Das Dravet-Syndrom (DS) ist ein seltenes, in der frühen Kindheit beginnendes, therapierefraktäres Epilepsiesyndrom, das mit einer hohen Morbidität und Mortalität verbunden ist. Fragestellung Ziele der Querschnittsstudie „Dravet syndrome caregiver survey“ (DISCUSS) sind die Identifizierung und Beschreibung der Faktoren, die einen Einfluss auf die Krankheitslast von Patienten mit DS und ihre Betreuer haben können. Die Ergebnisse der deutschen Kohorte werden vorgestellt. Material und Methoden Die Datenerhebung erfolgte durch eine anonyme Befragung von Eltern. Die Ergebnisse wurden für die verschiedenen Altersgruppen statistisch ausgewertet. Ergebnisse Der Fragebogen wurde von 68 Eltern der DS-Patienten mit einem durchschnittlichen Alter von 10 Jahren (Median: 9, Spanne: 1–26) ausgefüllt. Nur 3 Patienten (4,4 %) waren in den letzten 3 Monaten anfallsfrei. Insgesamt hatten 97 % der Patienten, die älter als 5 Jahre waren (n = 45), mindestens eine Komorbidität. Die zum Befragungszeitpunkt am häufigsten eingenommenen Antiepileptika waren Valproat, Kaliumbromid, Stiripentol, Clobazam und Topiramat. In der Vergangenheit wurden Natriumkanalblocker, Phenobarbital und Levetiracetam eingesetzt, aktuell fanden diese Antiepileptika nur selten Verwendung. Die Lebensqualität der Patienten war niedriger als die der Allgemeinbevölkerung. Die Erkrankung eines Familienmitglieds mit DS beeinflusst Eltern und Geschwister in hohem Maße. Diskussion Trotz individueller Kombinationstherapien sind die meisten Patienten mit DS nicht anfallsfrei. Insgesamt hat sich der Einsatz von beim DS wenig wirksamer Medikamente und der kontraindizierten Natriumkanalblocker zugunsten von wirksameren Medikamenten verschoben. Neue Therapie- und Versorgungskonzepte sind notwendig, um die Versorgung der Patienten mit DS zu verbessern und Eltern und Geschwister zu entlasten.

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Seizure management and prescription patterns of anticonvulsants in Dravet syndrome: A multicenter cohort study from Germany and review of literature

Cited by 28 publications

References 32 publications

A multicenter, matched case‐control analysis comparing burden‐of‐illness in Dravet syndrome to refractory epilepsy and seizure remission in patients and caregivers in Germany

A multicenter, matched case‐control analysis comparing burden‐of‐illness in Dravet syndrome to refractory epilepsy and seizure remission in patients and caregivers in Germany

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies

Klinische Charakteristika und Lebensqualität beim Dravet-Syndrom: Ergebnisse der deutschen Kohorte des „Dravet syndrome caregiver survey“ (DISCUSS)

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