Faculty Bibliography

PURPOSE/OBJECTIVE:The purpose of this study was to measure health-care resource utilization and costs in treatment-adherent, previously seizure-free patients with epilepsy who were treated in the inpatient/emergency room (ER) setting for new-onset seizures, compared with matched controls. METHODS:The study used a retrospective case/control study design using administrative claims from the IMS PharMetrics™ database. We identified adult patients with epilepsy with 1+ ER visit/hospitalization with primary diagnosis of epilepsy between 1/1/2006 and 3/31/2011, preceded by 6months of seizure-free activity and antiepileptic drug (AED) treatment adherence (≥80% of days covered by any AED); the first observed seizure defined the "breakthrough" seizure/index event. Treatment-adherent patients with epilepsy without any ER/hospital admission for seizures served as controls: an outpatient epilepsy-related medical claim within the selection window was chosen at random as the index date. The following were continuous enrollment requirements for all patients: ≥12-month pre- and ≥6-month postindex. Each case matched 1:1 to a control using propensity score matching. All-cause and epilepsy-related (epilepsy/convulsion diagnosis, AED pharmacy) resource utilization and unadjusted and adjusted direct health-care costs (per person, 2012 US dollars (USD)) were assessed in a 6-month follow-up period. PRINCIPAL RESULTS/RESULTS:There were 5729 cases and 14,437 controls eligible. The final sample comprised 5279 matched case/control pairs. In unadjusted analyses, matched cases had significantly higher rates of all-cause hospitalization and ER visits compared to controls and significantly higher total all-cause direct health-care costs (median $12,714 vs. $5095, p<0.001) and total epilepsy-related costs among cases vs. controls (median $7293 vs. $1712, p<0.001), driven by higher inpatient costs. Among cases, costs increased with each subsequent seizure (driven by inpatient costs). Cases had 2.3 times higher adjusted all-cause costs and 8.1 times higher adjusted epilepsy-related costs than controls (both p<0.001). CONCLUSION/CONCLUSIONS:Inpatient/ER-treated breakthrough seizures occurred among 28.4% of our treatment-adherent study sample and were associated with significant incremental health-care utilization and costs, primarily driven by hospitalizations. Our findings suggest the need for better seizure control via optimal patient management and the use of effective AED therapy, which can potentially lower health-care costs.

OBJECTIVE:To assess symptoms of attention-deficit/hyperactivity disorder (ADHD) and their impact among adults with epilepsy from a large community-based survey. METHODS:Adults who self-reported epilepsy were sent a postal survey including the Adult ADHD Self-Report Scale version 6 (ASRS-6), Physicians Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Assessment 7 (GAD-7), and questions about seizure frequency and number of antiepileptic drugs (AEDs) during the preceding 3 months. Individuals with ASRS-6 scores >14 were classified as ASRS+, and those with lower scores as ASRS-. Outcome measures included the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), Quality of Life and Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Sheehan Disability Scale (SDS). The relationship of ADHD symptoms to quality of life outcomes was modeled hierarchically, with linear regression controlling for sociodemographic covariates, comorbid depression and anxiety, seizure frequency, and number of AEDs. RESULTS:Among 1,361 of respondents with active epilepsy, 18.4% (n = 251) were classified as ASRS+ and at risk for ADHD. Compared to ASRS- cases, ASRS+ individuals were more likely to have elevated depression and anxiety scores as well as greater seizure frequency and more AED use (p < 0.05 for all). Modeling results comparing ASRS+ and ASRS- cases, controlling for all covariates, indicated that ASRS+ cases had lower quality of life (Beta [β] = -3.07, 95% confidence interval [CI] -4.19 to -1.96) and worse physical (β = -0.048 95% CI -0.076 to -0.020) and social functioning (β = -0.058, 95% CI -0.081 to -0.035) on the Q-LES-Q, and increases in family (β = 1.57, 95% CI 1.09-2.05), social (β = 1.68, 95% CI 1.20-2.16), and work-related disability (β-1.86, 95% CI 1.27-2.46). SIGNIFICANCE/CONCLUSIONS:ADHD symptoms occur in nearly one of five adults with epilepsy, and are associated with increased psychosocial morbidity and lowered QOL. Future studies should clarify the nature and causes of ADHD symptoms in adults with epilepsy.

OBJECTIVE: Perampanel, a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is indicated for adjunctive treatment of partial seizures in patients >/=12 years based on three phase III clinical studies. The perampanel U.S. Prescribing Information includes a boxed warning for serious psychiatric and behavioral adverse reactions. To provide context for this warning, detail on psychiatric and behavioral safety data from perampanel clinical studies is presented. METHODS: An analysis of pooled safety data from three phase III studies in patients with partial seizures is presented. Data from phase I and phase II studies in patients with and without epilepsy were also analyzed. Psychiatric and behavioral treatment-emergent adverse events (TEAEs) were evaluated according to Medical Dictionary for Regulatory Activities (MedDRA) terms, using "narrow" and "narrow-and-broad" standardized MedDRA queries (SMQs) for TEAEs suggestive of hostility/aggression. RESULTS: From the three phase III partial-seizure studies, the overall rate of psychiatric TEAEs was higher in the 8 mg (17.2%) and 12 mg (22.4%) perampanel groups versus placebo (12.4%). In the "narrow" SMQ, hostility/aggression TEAEs were observed in 2.8% for 8 mg and 6.3% for 12 mg perampanel groups, versus 0.7% of placebo patients. "Narrow-and-broad" SMQs for hostility/aggression TEAE rates were 12.3% for 8 mg and 20.4% for 12 mg perampanel groups, versus 5.7% for placebo; rates for events resulting in discontinuation were perampanel = 1.6% versus placebo = 0.7%. For events reported as serious AEs (SAEs), rates were perampanel = 0.7% versus placebo = 0.2%. In nonepilepsy patients, psychiatric TEAEs were similar between patients receiving perampanel and placebo. In phase I subjects/volunteers, all psychiatric TEAEs were mild or moderate. These analyses suggest that psychiatric adverse effects are associated with use of perampanel. SIGNIFICANCE: Patients and caregivers should be counseled regarding the potential risk of psychiatric and behavioral events with perampanel in patients with partial seizures; patients should be monitored for these events during treatment, especially during titration and at higher doses.