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

Abstract

Purpose: To evaluate long-term outcome of three years and treatment patterns of patients suffering from severely drug-refractory epilepsy (SDRE).

Methods: This 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.

Results: A 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.

Conclusion: SDRE 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.

Keywords: epidemiology; morbidity; population-based; secondary data analysis; seizure.

Figure 1

Prescription patterns of the anticonvulsants most used among severely drug-refractory epilepsy patients (FU, follow-up).

Figure 2

Prescription patterns of anticonvulsants of which <10% were used among severely drug-refractory epilepsy patients (FU, follow-up).

Figure 3

Annual inpatient admissions, epilepsy-specific admissions, and outpatient visits during baseline and FU in patients with epilepsy (FU, follow-up).

Figure 4

Comorbidities among patients with epilepsy and control group (FU, follow-up). (A) Hypertension, (B) depression, (C) gastrointestinal disorders, and (D) stroke, vascular disorders.

Figure 5

Injuries among patients with epilepsy and control group (FU, follow-up). (A) Injuries to trunk, limb, or body region (ICD-10 T08–T14), (B) injuries to the head (ICD-10 S00–S09), (C) injuries to the knee and lower leg (ICD-10 S80–S89), and (D) injuries to the ankle and foot (S90–S99).

Figure 6

Mortality among patients with epilepsy (A) and control group (B).

Figure 7

Annual inpatient treatment, medication, ancillary treatment, special equipment, outpatient visits, and dialysis costs, separately and as total direct costs.