Risk of hospitalization among patients with epilepsy using long versus short half-life adjunctive antiepileptic drugs

Abstract

While antiepileptic drugs (AEDs) remain the primary treatment for epilepsy, many patients continue to have seizures. Uncontrolled seizures may be related to AED half-life, since short half-life (SHL) AEDs require more frequent dosing compared with the simplified regimens of long half-life (LHL) AEDs. Long half-life AEDs may also improve seizure control by extending missed dose forgiveness periods. The value of LHL AEDs may be assessed as reduced healthcare utilization. The study's objective was to examine the impact of adding an LHL versus SHL adjunctive AED on the risk of hospitalizations in patients with uncontrolled epilepsy. Methods: This was a retrospective, longitudinal cohort study using the Symphony Health Solution Patient Integrated Dataverse. Patients ≥12 years old with uncontrolled epilepsy (≥2 medical claims ≥30 days apart) were identified during a study period (8/1/2012-7/31/2017). Patients were selected if they were subsequently initiated an adjunctive AED (excluding modified release formulations), and the prescription date served as the index. Patients were stratified into two mutually exclusive cohorts based on the index AED half-life (≤20 versus N 20 h). Poisson regressions with robust error variances were performed for the relative risks (RRs) of all-cause, epilepsy-related, and injury-related hospitalizations. Results: A total of 4984 patients were identified (2705 in the LHL and 2279 in the SHL cohort). Compared with those in the SHL cohort, patients in the LHL cohort were significantly younger [mean (SD, years): 43.9 (18.5) versus 49.2 (17.2), p b 0.001] and were less comorbid [mean (SD) of Charlson comorbidity index: 1.2 (1.8) versus 1.8 (2.2), p b 0.001]. In the one-year postindex date, adjusting for group differences, the risks of both all-cause and epilepsy-related hospitalizations were significantly lower in the LHL cohort than in the SHL cohort [all-cause: 0.84 (95% CI: 0.76-0.93), p = 0.0006; epilepsy-related: 0.83 (0.73-0.94), p = 0.0046].Injury-related hospitalizations did not differ between LHL and SHL cohorts. Conclusion:In patients with uncontrolled epilepsy who were initiated on an adjunctive AED, the choice of an LHL versus SHL was associated with significantly lower risks of all-cause and epilepsy-related hospitalizations.

Real-world impact of antiepileptic drug combinations with versus without perampanel on healthcare resource utilization in patients with epilepsy in the United States

“…PER has a particularly long half-life and a convenient once-daily dosing schedule [13]; this property may underlie part of the observed reduction in HRU among users of PER-based combinations. Indeed, a previous study showed that AEDs with longer half-lives are associated with significantly lower rates of allcause and epilepsy-related hospitalizations [34]. The long halflife (105 h) possibly provides an extended protection, and the once-daily dosing schedule may increase the likelihood that patients will adhere to treatment as opposed to a twice-daily regimens where a dose can be more easily missed.…”