The Burden of Severely Drug-Refractory Epilepsy: A Comparative Longitudinal Evaluation of Mortality, Morbidity, Resource Use, and Cost Using German Health Insurance Data

Abstract

PurposeTo evaluate long-term outcome of three years and treatment patterns of patients suffering from severely drug-refractory epilepsy (SDRE).MethodsThis analysis was population-based and retrospective, with data collected from four million individuals insured by statutory German health insurance. ICD-10 codes for epilepsy (G40*) and intake of anticonvulsants were used to identify prevalent cases, which were then compared with a matched cohort drawn from the population at large. Insurance data were available from 2008 to 2013. Any patient who had been prescribed with at least four different antiepileptic drugs (AEDs) in an 18-month period was defined as an SDRE case.ResultsA total of 769 patients with SDRE were identified. Of these, 19% were children and adolescents; the overall mean age was 42.3 years, 45.4% were female and 54.6% male. An average of 2.7 AEDs per patient was prescribed during the first follow-up year. The AEDs most commonly prescribed were: levetiracetam (53.5%), lamotrigine (41.4%), valproate (41.3%), lacosamide (20.4%), and topiramate (17.8%). During 3-year follow-up, there was an annual rate of hospitalization in the range 42.7 to 55%, which was significantly higher than the 11.6–12.8% (p < 0.001) for the matched controls. Admissions to hospital because of epilepsy ranged between 1.7 and 1.9 per year, with an average duration for each epilepsy-caused hospitalization of 10–11.1 days. The number of comorbidities for SDRE patients was significantly increased compared with the matched controls: depression (28% against 10%), vascular disorders (22% against 5%), and injury rates were also higher (head 16% against 3%, trunk and limbs 16% against 8%). The 3-year mortality rate for SDRE patients was 14% against 2.1% in the matched cohort.ConclusionSDRE patients are treated with AED polytherapy for all of the 3-year follow-up period. They are hospitalized more frequently than the general population and show increased morbidity levels and a sevenfold increase in mortality rate over 3 years. Further examination is required of ways in which new approaches to treatment could lead to better outcomes in severely affected patients.

Long-Term, Targeted Delivery of GDNF from Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy

“…The benefits of GDNF also appeared to extend beyond a simple symptomatic effect as it extended, even if in a less robust manner, well beyond removal of the devices. The concept of a potential disease-modifying effect is further supported by the observation that the reduction in seizure frequency was accompanied by improvements in cognition and anxiety, both significant comorbidities of epilepsy (Strzelczyk et al, 2017;Michaelis et al, 2018). These benefits occurred without classic signs of mistargeted neurotrophic factor delivery such as alterations in food consumption, changes in daily activity, or other overt neurobehavioral changes.…”

The direct cost of seizure events in severe childhood-onset epilepsies: A retrospective claims-based analysis

“…Using US health insurance claim data, Cramer et al reported that adults with uncontrolled epilepsy (added AEDs to existing therapy) had higher annual overall (medical and pharmacy) costs and epilepsyrelated costs than those with well-controlled epilepsy (no change in AED therapy) over a one-year period [3]. Similarly, using German health insurance data, Strzelczyk et al reported that patients with severe drug-refractory epilepsy had increased rates of hospitalization, with increased morbidity and mortality rates compared with the general population [22].…”

Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus

“…Furthermore, in contrast to the perceived excellent prognosis, up to 20% of GGE patients remain refractory to AEDs . Overall, patients with drug‐refractory epilepsies are affected by increased morbidity and mortality, social stigma, reduced employment opportunities, and impaired quality of life for both themselves and their caregivers . Introduction of a new AED provides an opportunity to achieve better seizure control for some patients .…”

“…6,7 Overall, patients with drug-refractory epilepsies are affected by increased morbidity and mortality, social stigma, reduced employment opportunities, and impaired quality of life for both themselves and their caregivers. [8][9][10][11][12] Introduction of a new AED provides an opportunity to achieve better seizure control for some patients. 13,14 Data on treatment of GGE with newer drugs not yet approved for treatment of GGE, such as lacosamide, zonisamide, and brivaracetam (BRV), remain scarce.…”