Seizure CostsQuality of life Depression a b s t r a c t Introduction: Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy.This study estimated cost, cost-driving factors and quality of life (QoL) in patients with Dravet syndrome and their caregivers in a prospective, multicenter study in Germany. Methods:A validated 3e12-month retrospective questionnaire and a prospective 3-month diary assessing clinical characteristics, QoL, and direct, indirect and out-of-pocket (OOP) costs were administered to caregivers of patients with DS throughout Germany.Results: Caregivers of 93 patients (mean age 10.1 years, ±7.1, range 15 monthse33.7 years) submitted questionnaires and 77 prospective diaries. The majority of patients (95%) experienced at least one seizure during the previous 12 months and 77% a status epilepticus (SE) at least once in their lives. Over 70% of patients had behavioural problems and delayed speech development and over 80% attention deficit symptoms and disturbance of motor skills and movement coordination. Patient QoL was lower than in the general population and 45% of caregivers had some form of depressive symptoms. Direct health care costs per three months were a mean of V6,043 ± V5,825 (median V4054, CI V4935-V7350) per patient. Inpatient costs formed the single most important cost category (28%, V1,702 ± V4,315), followed by care grade benefits (19%, V1,130 ± V805), anti-epileptic drug (AED) costs (15%, V892 ± V1,017) and ancillary treatments (9%, V559 ± V503). Total indirect costs were V4,399 ±V 4,989 (median V0, CI V3466-V5551) in mothers and V391 ± V1,352 (median V0, CI V195-V841) in fathers. In univariate analysis seizure frequency, experience of SE, nursing care level and severe additional symptoms were found to be associated with total direct healthcare costs. Severe additional symptoms was the single independently significant explanatory factor in a multivariate analysis. Conclusions:This study over a period up to 15 months revealed substantial direct and indirect healthcare costs of DS in Germany and highlights the relatively low patient and caregiver QoL compared with the general population.

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.

The aim of this study was to describe the treatment pattern of patients with Dravet syndrome (DS) in Germany with routine antiepileptic drugs (AEDs) and emergency medication, and to review the literature of realworld evidence on medicine utilization of patients with DS in Europe. Methods: Patient use of routine AEDs and emergency medications over 3-6 months was analyzed from a 2018 multicenter survey of 93 caregivers of patients with DS throughout Germany. Results were contextualized in a review of real-world evidence on medicine utilization of patients with DS in Europe. Results: The variety of medications and the most frequent combinations routinely used by patients with DS (AEDs and others) are described. Patients use a large number of pharmaceutical treatments to manage seizures. The five most commonly used AEDs were sodium valproate (66% of the patients; mean daily dose: 660 mg; 24.5 mg per kg bodyweight), bromide (44%; 1462 mg; 51.2 mg per kg), clobazam (41%; 10.4 mg; 0.32 mg per kg), stiripentol (35%; 797 mg; 27.6 mg per kg), and topiramate (24%; 107 mg; 3.5 mg per kg). Ninety percent had reported using emergency medications in the last 3 months;, with the most common medications being Buccolam (40%, an oromucosal form of midazolam) and diazepam (20%, mostly rectal application). No discernable relationships between current medication and age or seizure frequency were observed. Significance: This is the first comprehensive report of routine AEDs and emergency medication use in a large sample of patients with DS in Germany over a period of 3-6 months and shows that despite the most common

Zusammenfassung Fragestellung Ziel der prospektiven, multizentrischen Studie ist die Erfassung klinischer Charakteristika, des Ressourcenverbrauches sowie der Lebensqualität bei Patienten mit der Diagnose eines Dravet-Syndroms (DS) und deren Eltern in Deutschland. Methoden Die Datenerhebung erfolgte mit einem validierten retrospektiven Fragebogen über 3 bzw. 12 Monate sowie mit einem prospektiven Tagebuch über 3 Monate. Es wurden Daten zur Anfallssituation, Medikamenteneinnahme, Therapieinanspruchnahme sowie zu direkten und indirekten Kosten und zur Lebensqualität erhoben. Die Fragebögen und das Tagebuch wurden den Eltern über den Dravet-Syndrom e. V. sowie beteiligte Zentren ausgehändigt. Ergebnisse Der Fragebogen wurde von 93 Eltern der DS-Patienten und das Tagebuch von 77 ausgefüllt. Das mittlere Alter der Patienten betrug 10 Jahre (Spannweite 15 Monate bis 33,7 Jahre). Die Zeit bis zur Syndromdiagnose eines DS war in den letzten beiden Jahrzehnten deutlich kürzer. In den letzten 12 Monaten ereignete sich bei 95 % der Patienten mindestens ein epileptischer Anfall. Als anfallsauslösende Faktoren wurden Fieber (93,4 %), Aufregung (56 %), Schlafmangel (51,6 %) und starke körperliche Anstrengung (50,5 %) berichtet. Die Lebenszeitprävalenz des Status epilepticus lag bei 77 %, und bei 28 % war mindestens 1 Episode eines Status epilepticus innerhalb des letzten Jahres aufgetreten. Die Lebensqualität (QoL) der Patienten war niedriger als die der Allgemeinbevölkerung, und von 46 % der Eltern wurden Depressionssymptome berichtet. Die direkten Kosten in 3 Monaten betrugen 6043 € pro Patient. Den größten Kostenfaktor stellten die stationären Kosten dar (1702 €), gefolgt von den Leistungen für Pflege (1130 €), den Kosten für die antikonvulsiven Medikamente (892 €) und für Therapien (559 €). Bei den Müttern betrugen die gesamten indirekten Kosten 4399 € und bei den Vätern 391 € bezogen auf 3 Monate. Schlussfolgerung Das Dravet-Syndrom ist mit häufigen, oft therapierefraktären epileptischen Anfällen und Status epilepticus vergesellschaftet. Diese Studie zeigt die erhebliche Krankheitslast und die damit verbundenen Einschränkungen in der Lebensqualität sowie die hohen direkten und indirekten Kosten auf. Um eine Verbesserung der Lebensqualität bei Patienten mit DS und deren Eltern zu erreichen, bedarf es neuer Therapie- und Versorgungskonzepte.

worked in a year in Italy were derived from the public statistics database [2]. A oneway deterministic sensitivity analysis (DSA) was conducted to evaluate the variability of base case results in according to the parameters considered in the analysis. RESULTS: The economic model demonstrates an incremental annual productivity income of +V 1,355 for DMF treated patient vs IGAT patient (44% related to avoided absenteeism and 56% to increased presenteeism). The DSA demonstrate the robustness of base case result estimating the increased annual average productivity work in a range between +V 650 and +V 3,087. CONCLUSIONS: The economic model demonstrates that DMF treatment is associated with increased work productivity, suggesting greater indirect costs avoided, respect to ABCRE therapies from the Italian social perspective. Lee, A., et al.,