Real-world hospitalization risk in patients with epilepsy treated with perampanel

https://doi.org/10.1016/j.yebeh.2020.107270Get rights and content

Highlights

  • One-third of epilepsy patients fail to respond to antiepileptic drugs.

  • Patients with refractory epilepsy account for most of the burden of epilepsy.

  • Adherence to perampanel treatment was associated with reductions in hospitalizations and ED visits.

  • Findings support the theory that adjunctive AEDs may lead to better economic outcomes of treating refractory epilepsy.

Abstract

Aim

The aim of this study was to evaluate the risk of hospitalization and emergency department admission following initiation of perampanel treatment in patients with epilepsy.

Methods

This study is a retrospective longitudinal cohort study (Optum® Clinformatics® Datamart). Patients 4 to 11 years of age with a diagnosis of partial onset seizures or ≥ 12 years of age with primary generalized tonic–clonic seizures who had ≥ 1 perampanel prescription between 1/1/2014 and 3/31/2018 were eligible for the study. Additionally, patients were required to have 12-months of continuous enrollment before (pre-) and after (post-) the date of the first perampanel prescription (index-date). One-year relative-risks of all-cause and epilepsy-related hospitalizations and emergency department (ED) visits were estimated following initiation of perampanel treatment. Outcomes were also evaluated among a subsets of patients who were adherent to perampanel treatment, defined as a Medication Possession Ratio (MPR) ≥ 80%.

Results

A total of 320 patients were included in the study, mean age 38.2 ± 19 years, 56.6% female. In the overall population, the relative risks of hospitalizations or ED visits after perampanel initiation were not significantly different. Among the 145 patients who had an MPR ≥ 80%, initiation of perampanel treatment resulted in a significantly lower risk of epilepsy-related hospitalization (relative risk [RR] = 0.68, confidence interval [CI] [0.47, 0.98]), all-cause ED visits (RR = 0.80, CI [0.66, 0.98]), and epilepsy-related ED visits (RR = 0.74, CI [0.57, 0.95]) in the follow-up period.

Conclusions

Adherence to perampanel treatment was associated with significant reductions in one-year hospitalizations and ED visit risk in real world settings.

Introduction

Epilepsy, a chronic and debilitating disease affects 3.4 million individuals in the United States (US), including 470,000 children [1]. It is the fourth most common neurological disorder [2] with an estimated annual economic impact of approximately $15 billion (2004 dollars) in direct and indirect costs [3,4]. Despite the availability of multiple treatment options including vagus nerve stimulation, surgery, and diet control, initiation of monotherapy with an antiepileptic drug (AED) remains the cornerstone of epilepsy treatment [[5], [6], [7]]. Although half of the patients with new diagnosis achieve seizure freedom with their first, and nearly two-thirds do so with their second or third prescribed AED [8], between 20% and 40% of patients with epilepsy remain refractory to treatment [9,10].

Adjunctive or combination therapy with two different AEDs is considered in patients who fail to achieve adequate seizure control with monotherapy alone. Evidence suggests that combination therapy using AEDs with different mechanisms of action (MOA) might be more effective in patients with refractory epilepsy [11]. In a retrospective database study of patients with partial onset seizures (POS) receiving combination AED therapy, patients who received a gaba analog and an adjunctive AED with a different MOA had a significantly lower risk of inpatient hospitalization compared to those who received two gamma-aminobutyric acid (GABA) analogs [12].

Most AEDs act by attenuating calcium and/or sodium channels or enhancing inhibitory signals. Perampanel is the first orally active drug in a novel class of noncompetitive a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor antagonists. Perampanel is approved for the treatment POS and as adjunctive therapy for the treatment of primary generalized tonic–clonic (PGTC) seizures in patients with epilepsy ≥ 12 years of age, and for the treatment of POS in pediatric patients 4–11 years old [13].

Medication adherence is particularly important in epilepsy because consequences of nonadherence in terms of breakthrough seizures [14] can have a substantial impact on patient quality of life [15]. Evidence also suggests that nonadherence to AED therapy results in potentially higher healthcare resource utilization and costs. In a study of patients with epilepsy in a Medicaid population, patients who were nonadherent to AED therapy, defined as a Medication Possession Ratio (MPR) < 80%, had higher inpatient (and emergency department [ED] services costs compared to patients who were adherent [MPR ≥ 80%]) [16].

Our objective was to evaluate the risk of hospitalization and emergency department admissions following initiation of perampanel treatment in adults and children with epilepsy in clinical practice. Given the critical role of medication adherence in epilepsy management, we also evaluated study outcomes in a subset of patients who were adherent to perampanel treatment.

Section snippets

Data source

This real-world retrospective longitudinal (pre vs. post) cohort study was conducted using deidentified administrative claims data from the Optum® Clinformatics® Datamart from January 1, 2014 to March 31, 2018.1 The Optum database contains a longitudinal record of deidentified medical (e.g., inpatient and outpatient services) and pharmacy claims (e.g.,

Sample selection and demographic characteristics

A total of 975 patients received at least one prescription for perampanel during the fifty-month study identification period, 418 of whom had 12-months of continuous enrollments prior to, and postinitiation of perampanel treatment. Of these, 18 patients did not have at least two medical claims with a diagnosis of epilepsy or convulsive seizures during the preindex period, three patients were less than 4 years of age at baseline, and 77 patients did not have diagnoses codes consistent with the

Discussion

Evidence suggests that adjunctive therapy with an AED with a different MOA than the primary AED is associated with better outcomes [11,12]. It has also been postulated that patients with refractory epilepsy might benefit from adjunctive therapies with novel MOAs [20]. Perampanel is the first orally active drug in a novel class of noncompetitive aamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type glutamate receptor antagonists and is approved for the treatment of POS and as adjunctive

Declaration of competing interest

Xuan Li, Feride Frech, Craig Plauschinat are employees of Eisai, Inc.

References (22)

  • National Institute for Health and Clinical Excellence

    Epilepsies: the diagnosis and management. NICE clinical guideline 137 [updated April 2018]

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      Epilepsy is a chronic neurological condition that affects nearly 50 million people worldwide (World Health Organization, 2019). However, one-third of patients fail to respond to the available antiepileptic drugs (AEDs), developing refractory epilepsy (Biase et al., 2018; Li et al., 2021; Patsalos, 2015). This is one of the main reasons for continuing to develop new generation AEDs with better efficacy and safety, as it is perampanel (PER), a highly potent third generation AED (LaPenna and Tormoehlen, 2017; Patsalos, 2015).

    • Effects of Epidiolex® (Cannabidiol) on seizure-related emergency department visits and hospital admissions: A retrospective cohort study

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      Furthermore Li et al investigated the impact on perampanel in real-world settings on ED and hospital admissions. In 320 adult and pediatric patients, it was demonstrated that while the overall relative risk of hospitalization or ED visits was not statistically different, those with demonstrated adherence to perampanel therapy had associations with significant reduction in one-year ED visits and hospitalizations in the real world [25]. The results of this study shed insight into some of the limitations of these studies where adherence to intervention is variable.

    • Use of extended-release and immediate-release anti-seizure medications with a long half-life to improve adherence in epilepsy: A guide for clinicians

      2021, Epilepsy and Behavior
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      However, the authors noted that a limitation of the analysis is that a causal relationship between missing a dose (for those who had been taking ASMs for a long period) and having or not having seizures as a consequence could not be established. For patients who regularly miss doses, this non-adherence can translate into a higher incidence of hospitalization, total inpatient days, emergency department visits, and correspondingly higher costs (Table 2; [30,44–54]). For example, in a 44-month observational, prospective study involving 282 consecutive patients with epilepsy (aged > 16 years) who were acutely hospitalized for single or serial seizures, 39% were found to be non-adherent (defined as having a serum concentration/dose [c/d] ratio of < 50% of the control c/d ratio [each patient being his/her own control]) and so poor adherence was considered an important reason for the breakthrough seizures in these patients [49].

    This study was funded by Eisai, Inc.

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