Brivaracetam effectiveness and tolerability in older and younger adults with epilepsy: EXPERIENCE, a pooled analysis of international data from retrospective studies.

This analysis assessed the effectiveness and tolerability of brivaracetam (BRV) in older (≥65 years of age) and younger (≥16 to <65 years of age) adults with epilepsy. This was a subgroup analysis from EXPERIENCE/EPD332, a pooled analysis of individual patient records from multiple independent, non-interventional studies of patients with epilepsy starting BRV in Australia, Europe, and the United States. Included patients had ≥6 months of follow-up data. Outcomes included responders (≥50 % reduction from baseline in seizure frequency), seizure freedom (no seizures within 3 months before the time point), and continuous seizure freedom (no seizures from baseline) at 12 months; BRV discontinuation during the whole study follow-up; and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were deemed non-responders/not seizure-free. Analysis populations included the Full Analysis Set (FAS; patients who received ≥1 BRV dose and had seizure type and age documented at baseline) and the modified FAS (FAS patients who had ≥1 seizure recorded during baseline). The FAS was used for all outcomes except seizure reduction. The FAS included 147 (8.9 %) patients aged ≥65 years and 1497 (91.1 %) aged ≥16 to <65 years. Compared with the younger subgroup, patients aged ≥65 years had a longer median epilepsy duration (33.0 years [n = 144] vs 17.0 years [n = 1460]) and lower median seizure frequency at index (2.0 seizures/28 days [n = 129] vs 4.0 seizures/28 days [n = 1256]), and less commonly had >1 prior antiseizure medication (106/141 [75.2 %] vs 1265/1479 [85.5 %]). At 12 months, a numerically higher percentage of patients aged ≥65 years versus the younger subgroup achieved ≥50 % seizure reduction (46.5 % [n = 71] vs 36.0 % [n = 751]), seizure freedom (26.0 % [n = 100] vs 13.9 % [n = 1011]), and continuous seizure freedom (22.0 % [n = 100] vs 10.7 % [n = 1011]). During the whole study follow-up, 43/147 (29.3 %) patients aged ≥65 years and 508/1492 (34.0 %) aged ≥16 to <65 years discontinued BRV. The incidence of TEAEs since the prior visit was similar in both subgroups at 3 months (≥65 years vs ≥16 to <65 years: 38/138 [27.5 %] vs 356/1404 [25.4 %]), 6 months (19/119 [16.0 %] vs 176/1257 [14.0 %]), and 12 months (8/104 [7.7 %] vs 107/1128 [9.5 %]). This real-world analysis suggests BRV was effective in patients aged ≥65 years and ≥16 to <65 years, with numerically higher effectiveness in the older subgroup. BRV was well tolerated in both subgroups.

Management of epilepsy in older adults: A critical review by the ILAE Task Force on Epilepsy in the elderly.

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.

The epidemiology of epilepsy in older adults: A narrative review by the ILAE Task Force on Epilepsy in the Elderly.

In an aging world, it is important to know the burden of epilepsy affecting populations of older persons. We performed a selective review of epidemiological studies that we considered to be most informative, trying to include data from all parts of the world. We emphasized primary reports rather than review articles. We reviewed studies reporting the incidence and prevalence of epilepsy that focused on an older population as well as studies that included a wider age range if older persons were tabulated as a subgroup. There is strong evidence that persons older than approximately 60 years incur an increasing risk of both acute symptomatic seizures and epilepsy. In wealthier countries, the incidence of epilepsy increases sharply after age 60 or 65 years. This phenomenon was not always observed among reports from populations with lower socioeconomic status. This discrepancy may reflect differences in etiologies, methods of ascertainment, or distribution of ages; this is an area for more research. We identified other areas for which there are inadequate data. Incidence data are scarcer than prevalence data and are missing for large areas of the world. Prevalence is lower than would be expected from cumulative incidence, possibly because of remissions, excess mortality, or misdiagnosis of acute symptomatic seizures as epilepsy. Segmentation by age, frailty, and comorbidities is desirable, because "epilepsy in the elderly" is otherwise too broad a concept. Data are needed on rates of status epilepticus and drug-resistant epilepsy using the newer definitions. Many more data are needed from low-income populations and from developing countries. Greater awareness of the high rates of seizures among older adults should lead to more focused diagnostic efforts for individuals. Accurate data on epilepsy among older adults should drive proper allocation of treatments for individuals and resources for societies.

Economic aspects of treating seizure clusters.

Seizure clusters may initiate a chain of events that have economic as well as clinical consequences. The potential economic consequences of seizure clusters must be weighed against the cost of medication to attenuate them. This is true both for individual patients and for society. Data needed for economic analyses include the chance that a cluster will progress to an adverse outcome, such as a need for emergency care, the costs of such an outcome, the cost of a rescue medication (RM), and the effectiveness of the RM. Indirect costs, such as lost employment for patients and caregivers, must also be considered. Several types of economic analyses can be used to determine costs and benefits of a medical intervention. There are studies comparing different RMs from an economic perspective, but there is little direct information on the costs of using an RM versus allowing clusters to run their course. However, the high expense of consequences of seizure clusters makes it likely that effective RMs will make economic as well as medical sense for many patients.

Quality-of-life results in adults with epilepsy using diazepam nasal spray for seizure clusters from a long-term, open-label safety study.

BACKGROUND: The impact of seizure clusters and the use of intermittent rescue therapy for clusters on the quality of life (QoL) of patients with epilepsy has not been widely studied. The present analysis assessed QoL as a secondary endpoint among adult patients with seizure clusters enrolled in a long-term, phase 3, open-label safety study (NCT02721069) of diazepam nasal spray (Valtoco®). The QoL aspect of patients in this study has not been previously published. METHODS: The 12-month safety study of diazepam nasal spray enrolled patients aged 6-65 years with seizure clusters. Adults aged ≥18 years completed the Quality of Life in Epilepsy (QOLIE)-31-P at baseline (day 0) and days 30, 150, 270, and 365. This instrument includes questions about patient health and daily activities with numeric values (1-100) assigned to responses; higher scores indicate better QoL. The QOLIE-31-P includes 7 subscales: Seizure Worry, Overall QoL, Emotional Well-Being, Energy/Fatigue, Cognitive Functioning, Medication Effects, and Social Functioning; an Overall Score is calculated as a weighted composite of the 7 subscales. Comparisons were made between subgroups of patients who had frequent (≥2) and infrequent (<2) monthly dosing of diazepam nasal spray and those whose doses were administered by the patient or a care partner. This safety study was not powered to assess efficacy endpoints; descriptive statistics were calculated across time points. In addition, safety measures, including treatment-emergent adverse events, are reported. RESULTS: Seventy-two adults who responded to the QOLIE-31-P were included in the analyses. Mean QOLIE-31-P scores were stable or increased across time points. The mean total scores increased from day 0 to day 365 by 5.2 among patients providing data for ≥1 time point (follow-up group) and 2.2 among patients providing data at all time points (QOLIE all-assessments subgroup). Subscale means for Seizure Worry and Social Functioning showed the greatest numeric increase from baseline. Mean QOLIE-31-P scores were similar in all subgroups. The safety profile in the follow-up group was similar to that seen in all study adults. CONCLUSIONS: Adults with refractory epilepsy who were treated with diazepam nasal spray for seizure clusters maintained or improved QOLIE subscale scores across the 12-month study period. Seizure Worry and Social Functioning subscale scores increased over time, suggesting improvement in these domains for this population with intractable epilepsy. Changes among subscale results suggest differences in sensitivity to the use of an intermittent treatment. The potential to improve patient function with treatment for seizure clusters warrants further study.

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

OBJECTIVES: Combination regimens of antiepileptic drugs (AEDs) with various mechanisms of action (MOA) are commonly used in patients with refractory epilepsy. However, outcomes related to combination AEDs with novel MOA, such as perampanel (PER), are not well described. This study compared healthcare resource utilization (HRU) among recipients of PER-based combinations versus recipients of other non-PER-based combinations. METHODS: This retrospective study used claims data from the Symphony Health's IDV® (Integrated Dataverse) database (August 2012 to July 2018). Patients were aged ≥12 years with epilepsy or non-febrile convulsions, were treated with AED combinations, and had ≥12 and ≥6 months pre- and post-index date, respectively (date of initiation of the second AED in the combination). AEDs were categorized based on MOA: selective non-competitive antagonist of AMPA receptors (i.e., PER), sodium channel blocker (SC), synaptic vesicle protein 2A binding (SV2), and gamma-aminobutyric acid analog (G). Patients were then classified into MOA-based cohorts: PER + SC, PER + SV2, PER + G, SC + SC, SC + SV2, SC + G, SV2 + G, and G + G. HRU outcomes were evaluated during follow-up and compared between PER-based cohorts and non-PER-based cohorts. RESULTS: On average, patients in the PER + SC (N = 3,592), PER + SV2 (N = 2,200), and PER + G (N = 1,313) cohorts were younger and had a lower Quan-Charlson comorbidity index than those in non-PER-based cohorts. PER + SC and PER + SV2 users had significantly fewer all-cause hospitalizations than non-PER-based users (adjusted RR range: 0.66-0.89, all P < 0.05), while PER + G recipients had fewer all-cause hospitalizations than recipients of SV2 + G and G + G (adjusted RR range: 0.92-0.94). Similar trends were observed for epilepsy-related hospitalizations. Across all comparisons, PER-based combinations were associated with significantly lower rates of all-cause clinic/office/outpatient visits relative to non-PER-based combinations (adjusted RR range: 0.69-0.86, all P < 0.05). SIGNIFICANCE: Results showed that patients treated with PER-based combinations had fewer all-cause and epilepsy-related hospitalizations, and fewer all-cause clinic/office/outpatient visits compared with patients treated with most other non-PER-based combinations.

High health care costs in minority groups of older US Medicare beneficiaries with epilepsy.

OBJECTIVE: To examine health care costs in diverse older Medicare beneficiaries with epilepsy. METHODS: Using 2008-2010 claims data, we conducted a longitudinal cohort study of a random sample of Medicare beneficiaries augmented for minority representation. Epilepsy cases (n = 36 912) had ≥1 International Classification of Diseases, Ninth Edition (ICD-9) 345.x or ≥2 ICD-9 780.3x claims, and ≥1 antiepileptic drug (AED) in 2009; new cases (n = 3706) had no seizure/epilepsy claims nor AEDs in the previous 365 days. Costs were measured by reimbursements for all care received. High cost was defined as follow-up 1-year cost ≥ 75th percentile. Logistic regressions examined association of high cost with race/ethnicity, adjusting for demographic, clinical, economic, and treatment quality factors. In cases with continuous 2-year data, we obtained costs in two 6-month periods before and two after the index event. RESULTS: Cohort was ~62% African Americans (AAs), 11% Hispanics, 5% Asians, and 2% American Indian/Alaska Natives. Mean costs in the follow-up were ~$30 000 (median = $11 547; new cases, mean = $44 642; median = $25 008). About 19% white compared to 27% AA cases had high cost. AA had higher odds of high cost in adjusted analyses (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.11-1.29), although this was only marginally significant when adjusting for AED adherence (OR = 1.09, 95% CI = 1.01-1.18, P = 0.03). Factors associated with high cost included ≥1 comorbidity, neurological care, and low AED adherence. Costs were highest at ~$17 000 in the 6 months immediately before and after the index event (>$29 000 for new cases). SIGNIFICANCE: The financial sequelae of epilepsy among older Americans disproportionally affect minorities. Studies should examine contributors to high costs.

Risk of pharmacokinetic interactions between antiepileptic and other drugs in older persons and factors associated with risk.

OBJECTIVE: To determine the frequency of older Americans with epilepsy receiving concomitant prescriptions for antiepileptic drugs (AEDs) and non-epilepsy drugs (NEDs) which could result in significant pharmacokinetic (PK) interaction, and to assess the contributions of racial/ethnic, socioeconomic, and demographic factors. METHODS: Retrospective analyses of 2008-2010 Medicare claims for a 5% random sample of beneficiaries ≥67 years old in 2009 augmented for minority representation. Prevalent cases had ≥1 ICD-9 345.x or ≥2 ICD-9 780.3x, and ≥1 AED. Among them, incident cases had no seizure/epilepsy claim codes nor AEDs in preceding 365 days. Drug claims for AEDs, and for the 50 most common NEDs within +/- 60 days of the index epilepsy date were tabulated. Interacting pairs of AEDs/NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. RESULTS: Interacting drug pairs affecting NED efficacy were found in 24.5% of incident, 39% of prevalent cases. Combinations affecting AED efficacy were found in 20.4% of incident, 29.3% of prevalent cases. Factors predicting higher interaction risk included having ≥ 1 comorbidity, being eligible for Part D low Income Subsidy, and not living in the northeastern US. Protective factors were Asian race/ethnicity, and treatment by a neurologist. SIGNIFICANCE: A substantial portion of older epilepsy patients received NED-AED combinations that could cause important PK interactions. The lower frequency among incident vs. prevalent cases may reflect changes in prescribing practices. Avoidance of interacting AEDs is feasible for most persons because of the availability of newer drugs.

The Impact of Interictal Discharges on Performance.

PURPOSE OF REVIEW: Our purpose is to review evidence relating to the concept that interictal epileptiform discharges (IEDs) impair brain performance. RECENT FINDINGS: Sophisticated measures of motor and cognitive performance have clarified older observations, confirming that in both animals and humans, IEDs affect aspects of performance, IED morphology, frequency, anatomical distribution, and duration matter. However, we now know that it is difficult to draw a line between IEDs and seizures, not only by electrical criteria but even by metabolic and molecular measures. IEDs impair performance acutely and probably chronically. Thus, there are good theoretical reasons for suppressing them, but no consensus has been reached on how much effort this deserves. Many antiepileptic medications effective for control of clinical seizures have little effect on IEDs. Better methods of measuring outcomes may allow selection of individual patients for whom treatment aimed at IEDs is worthwhile.

Patient characteristics and treatment patterns in patients with newly diagnosed epilepsy: A US database analysis.

OBJECTIVE: The objective of this study was to determine patient characteristics and antiepileptic drug (AED) treatment patterns in patients with newly diagnosed epilepsy in a United States (US) population followed for ≥180 days. METHODS: In this retrospective cohort study, Commercial, Supplemental Medicare, and Medicaid insurance claims from US-based Truven Health MarketScan® claims database were analyzed for incident epilepsy cases (index date: January 2010-June 2013; prior baseline of 2 years [1 year for ages 1 to <2 years; none for those <1 year]). Cases met epilepsy criteria consistent with the International League Against Epilepsy diagnostic guidelines, with continuous medical and pharmacy enrollment without an epilepsy or seizure diagnosis or AED prescription during baseline. Treatment was classified as monotherapy (one AED for ≥90 continuous days), polytherapy (at least two AEDs for ≥90 days), or untreated (no AED claims but other pharmacy or healthcare claims). Treatment pattern comparisons used matched cohorts across seizure types. RESULTS: Of 58,757 incident cases, 50,838 had a follow-up of ≥180 days. The median (range) follow-up duration was 529 (180-1096) days. Patient characteristics were similar across seizure types (matched focal vs. generalized epilepsy, N = 9949 each). At 6 and 12 months post-index, 46.8% and 52.2% of patients, respectively, had received AED treatment. Of 29,226 patients receiving treatment, 74.7% and 1.6% received monotherapy and polytherapy for ≥90 days, respectively, as first-line treatment; remaining patients received AED for <90 days and were excluded. The probability of remaining on initial treatment after 1 year was 61.0% for monotherapy and 36.5% for polytherapy. The most common first-line AEDs were levetiracetam (44.4%), phenytoin (6.5%), valproic acid (6.4%), lamotrigine (6.3%), oxcarbazepine (5.7%), topiramate (5.5%), and gabapentin (5.3%). CONCLUSION: Although the majority of treated patients received AED monotherapy consistent with guidelines, suboptimal rates of AED treatment and persistence of first-line treatment after initial epilepsy diagnosis suggest that efforts are needed to improve patient care.

Quality of Antiepileptic Treatment Among Older Medicare Beneficiaries With Epilepsy: A Retrospective Claims Data Analysis.

BACKGROUND: Enzyme-inducing antiepileptic drugs (EI-AEDs) are not recommended for older adults with epilepsy. Quality Indicator for Epilepsy Treatment 9 (QUIET-9) states that new patients should not receive EI-AEDs as first line of treatment. In light of reported racial/ethnic disparities in epilepsy care, we investigated EI-AED use and QUIET-9 concordance across major racial/ethnic groups of Medicare beneficiaries. RESEARCH DESIGN: Retrospective analyses of 2008-2010 Medicare claims for a 5% random sample of beneficiaries 67 years old and above in 2009 augmented for minority representation. Logistic regressions examined QUIET-9 concordance differences by race/ethnicity adjusting for individual, socioeconomic, and geography factors. SUBJECTS: Epilepsy prevalent (≥1 International Classification of Disease-version 9 code 345.x or ≥2 International Classification of Disease-version 9 code 780.3x, ≥1 AED), and new (same as prevalent+no seizure/epilepsy events nor AEDs in 365 d before index event) cases. MEASURES: Use of EI-AEDs and QUIET-9 concordance (no EI-AEDs for the first 2 AEDs). RESULTS: Cases were 21% white, 58% African American, 12% Hispanic, 6% Asian, 2% American Indian/Alaskan Native. About 65% of prevalent, 43.6% of new cases, used EI-AEDs. QUIET-9 concordance was found for 71% Asian, 65% white, 61% Hispanic, 57% African American, 55% American Indian/Alaskan new cases: racial/ethnic differences were not significant in adjusted model. Beneficiaries without neurology care, in deductible drug benefit phase, or in high poverty areas were less likely to have QUIET-9 concordant care. CONCLUSIONS: EI-AED use is high, and concordance with recommendations low, among all racial/ethnic groups of older adults with epilepsy. Potential socioeconomic disparities and drug coverage plans may affect treatment quality and opportunities to live well with epilepsy.

What does the U.S. Medicare administrative claims database tell us about initial antiepileptic drug treatment for older adults with new-onset epilepsy?

OBJECTIVE: Disparities in epilepsy treatment are not uncommon; therefore, we examined population-based estimates of initial antiepileptic drugs (AEDs) in new-onset epilepsy among racial/ethnic minority groups of older US Medicare beneficiaries. METHODS: We conducted retrospective analyses of 2008-2010 Medicare administrative claims for a 5% random sample of beneficiaries augmented for minority representation. New-onset epilepsy cases in 2009 had ≥1 International Classification of Diseases, Ninth Revision (ICD-9) 345.x or ≥2 ICD-9 780.3x, and ≥1 AED, AND no seizure/epilepsy claim codes or AEDs in preceding 365 days. We examined AED use and concordance with Quality Indicators of Epilepsy Treatment (QUIET) 6 (monotherapy as initial treatment = ≥30 day first prescription with no other concomitant AEDs), and prompt AED treatment (first AED within 30 days of diagnosis). Logistic regression examined likelihood of prompt treatment by demographic (race/ethnicity, gender, age), clinical (number of comorbid conditions, neurology care, index event occurring in the emergency room (ER)), and economic (Part D coverage phase, eligibility for Part D Low Income Subsidy [LIS], and ZIP code level poverty) factors. RESULTS: Over 1 year of follow-up, 79.6% of 3,706 new epilepsy cases had one AED only (77.89% of whites vs. 89% of American Indian/Alaska Native [AI/AN]). Levetiracetam was the most commonly prescribed AED (45.5%: from 24.6% AI/AN to 55.0% whites). The second most common was phenytoin (30.6%: from 18.8% Asians to 43.1% AI/AN). QUIET 6 concordance was 94.7% (93.9% for whites to 97.3% of AI/AN). Only 50% received prompt AED therapy (49.6% whites to 53.9% AI/AN). Race/ethnicity was not significantly associated with AED patterns, monotherapy use, or prompt treatment. SIGNIFICANCE: Monotherapy is common across all racial/ethnic groups of older adults with new-onset epilepsy, older AEDs are commonly prescribed, and treatment is frequently delayed. Further studies on reasons for treatment delays are warranted. Interventions should be developed and tested to develop paradigms that lead to better care.

Health care resource utilization before and after perampanel initiation among patients with epilepsy in the United States.

OBJECTIVE: The purpose of this study was to evaluate changes in health care resource utilization following the initiation of perampanel for the treatment of epilepsy in the United States. METHODS: Health care claims from Symphony Health's Integrated Dataverse database between December 2012 and November 2015 were analyzed. Patients newly initiated on perampanel, having ≥1 epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 345.xx, ICD-10-CM code G40.xxx) or nonfebrile convulsion (ICD-9-CM code 780.39, ICD-10-CM code R56.9) diagnosis, and having ≥6 months of baseline and observation periods were included. Patients <12 years old at perampanel initiation were excluded. RESULTS: Of the 2,508 perampanel patients included in the study, the mean [median] (±standard deviation [SD]) age was 35.8 [34] (±16.0) years and 56.2% were female. The mean [median] (±SD) observation duration was 459.8 [462] (±146.3) days in the postperampanel period. The postperampanel period was associated with significantly lower rates of all health care resource utilization outcomes than the pre-period. For the post- versus pre-period, perampanel users had 42.3 versus 53.8 overall hospitalizations per 100 person-years (rate ratio [RR] = 0.80, p < 0.001) and 1,240.2 versus 1,343.8 outpatient visits per 100 person-years (RR = 0.91, p < 0.001). Epilepsy-related hospitalizations and outpatient visits were 25.2 versus 33.6 per 100 person-years (RR = 0.76, p < 0.001) and 327.0 versus 389.0 per 100 person-years (RR = 0.84, p < 0.001), respectively. Additionally, a significantly lower rate of status epilepticus in the post-period (1.8 events per 100 person-years) was observed compared to the pre-period (4.4 events per 100 person-years; RR = 0.43, p < 0.001). The monthly time trend of hospitalizations showed an increasing trend leading up to the initiation of perampanel, after which the hospitalizations decreased steadily. SIGNIFICANCE: Use of perampanel for the treatment of epilepsy was associated with significant reduction in all-cause and epilepsy-related health care resource utilization, including hospitalizations, especially for status epilepticus, and outpatient visits.

Detection of generalized tonic-clonic seizures using surface electromyographic monitoring.

OBJECTIVE: A prospective multicenter phase III trial was undertaken to evaluate the performance and tolerability in the epilepsy monitoring unit (EMU) of an investigational wearable surface electromyographic (sEMG) monitoring system for the detection of generalized tonic-clonic seizures (GTCSs). METHODS: One hundred ninety-nine patients with a history of GTCSs who were admitted to the EMU in 11 level IV epilepsy centers for clinically indicated video-electroencephalographic monitoring also received sEMG monitoring with a wearable device that was worn on the arm over the biceps muscle. All recorded sEMG data were processed at a central site using a previously developed detection algorithm. Detected GTCSs were compared to events verified by a majority of three expert reviewers. RESULTS: For all subjects, the detection algorithm detected 35 of 46 (76%, 95% confidence interval [CI] = 0.61-0.87) of the GTCSs, with a positive predictive value (PPV) of 0.03 and a mean false alarm rate (FAR) of 2.52 per 24 h. For data recorded while the device was placed over the midline of the biceps muscle, the system detected 29 of 29 GTCSs (100%, 95% CI = 0.88-1.00), with a detection delay averaging 7.70 s, a PPV of 6.2%, and a mean FAR of 1.44 per 24 h. Mild to moderate adverse events were reported in 28% (55 of 199) of subjects and led to study withdrawal in 9% (17 of 199). These adverse events consisted mostly of skin irritation caused by the electrode patch that resolved without treatment. No serious adverse events were reported. SIGNIFICANCE: Detection of GTCSs using an sEMG monitoring device on the biceps is feasible. Proper positioning of this device is important for accuracy, and for some patients, minimizing the number of false positives may be challenging.

Adherence to antiepileptic drugs among diverse older Americans on Part D Medicare.

INTRODUCTION: Older minority groups are more likely to have poor AED adherence. We describe adherence to antiepileptic drugs (AEDs) among older Americans with epilepsy. METHODS: In retrospective analyses of 2008-2010 Medicare claims for a 5% random sample of beneficiaries augmented by minority representation, epilepsy cases in 2009 were those with ≥1 claim with ICD-9345.x or ≥2 with 780.3x, and ≥1 AED. New-onset cases had no such claims or AEDs in the year before the 2009 index event. We calculated the Proportion of Days Covered (PDC) (days with ≥1 AED over total follow-up days) and used logistic regression to estimate associations of non-adherence (PDC <0.8) with minority group adjusting for covariates. RESULTS: Of 36,912 epilepsy cases (19.2% White, 62.5% African American (AA), 11.3% Hispanic, 5.0% Asian and 2% American Indian/Alaskan Native), 31.8% were non-adherent (range: 24.1% Whites to 34.3% AAs). Of 3706 new-onset cases, 37% were non-adherent (range: 28.7% Whites to 40.5% AAs). In adjusted analyses, associations with minority group were significant among prevalent cases, and for AA and Asians vs. Whites among new cases. Among other findings, beneficiaries from high-poverty ZIP codes were more likely to be non-adherent than their counterparts, and those in cost-sharing drug benefit phases were less likely to be non-adherent than those in deductible phases. CONCLUSION: About a third of older adults with epilepsy have poor AED adherence; minorities are more likely than Whites. Investigations of reasons for non-adherence, and interventions to promote adherence, are needed with particular attention to the effect of cost-sharing and poverty.

Quality Indicator for Epilepsy Treatment 15 (QUIET-15): Intervening after recurrent seizures in the elderly.

In this study, we examined the provision of care to older adults with epilepsy and compliance with the "Quality Indicator for Epilepsy Treatment 15" (QUIET-15) measure. We analyzed 2008-2010, 5% random sample of Medicare beneficiaries augmented with data from all beneficiaries who identified as a minority with claims related to seizures (780.3x) or epilepsy (345.xx). Of 36,912 identified epilepsy cases, 12.6% had ≥1 emergency room (ER) visit for seizure(s). For those who presented to ER, among those taking anti-epileptic drugs (AEDs), AED was changed in 15.4%, dose adjusted in 19.7%, and stopped in 14.9%; among those not taking AED, therapy was initiated in 68.5%. In adjusted logistic regressions, African-Americans were more likely to have recurrent seizures than Whites (OR 1.41, 95%CI 1.27-1.56), while Asians were less likely to have recurrent seizures (OR 0.71, 95%CI 0.57-0.89). There were no significant racial/ethnic differences in the likelihood of a post-seizure intervention. The chance of seizure recurrence leading to ER visit decreased with age and increased with the number of comorbidities. Patients with seizure recurrence were more likely to be taking an enzyme-inducing AED (OR 1.69, 95%CI 1.57-1.82) and receiving Part D Low Income Subsidy (OR 1.36, 95%CI 1.22-1.51). The probability of AED change after a seizure was higher for patients with ≥4 comorbidities (OR 1.69, 95%CI 1.25-2.27), patients who saw a neurologist (OR 1.49, 95%CI 1.30-1.70), and patients who were taking an enzyme-inducing AED (OR 1.47, 95%CI 1.27-1.71). Overall, a minority of Medicare beneficiaries experienced seizure recurrence that resulted in an ER visit. However, only half of them received treatment concordant with QUIET-15. Though racial differences were observed in occurrence of seizures, none were noted in the provision of care.

Understanding the burden of idiopathic generalized epilepsy in the United States, Europe, and Brazil: An analysis from the National Health and Wellness Survey.

The aim of this study was to understand the current burden of primary generalized tonic-clonic seizures (PGTCS) associated with idiopathic generalized epilepsy (IGE) as a function of seizure frequency. We analyzed data for (IGE) as a proxy measure of PGTCS. Little is known about the quality of life (QoL), health utility, productivity, healthcare resource utilization (HRU), and cost burden of PGTCS or IGE. Patients were identified from the US (2011, 2012, & 2013), 5EU (2011 & 2013), and Brazil (2011 & 2012) National Health and Wellness Survey, a nationally representative, internet-based survey of adults (18+ years). Patients that self-reported a diagnosis of IGE were categorized into seizure frequencies of: ≥1 seizure per week, 1-3 seizures per month, 1-4 seizures per year, or <1 seizure per year. QoL was measured using the SF-36v2 Mental (MCS) and Physical Component Summary (PCS) scores, health utilities with the SF-6D, productivity with the Work Productivity and Activity Impairment (WPAI) questionnaire, and HRU as reported in the past six months. Unit costs were estimated from the literature and multiplied against HRU values to calculate direct costs and WPAI values to calculate indirect costs. Generalized linear regression was utilized to examine the relationship between seizure frequency and each measure of burden with adjustment for covariates. Out of the general population surveyed, IGE was self-reported in 782 of 176,093 (US), 172 of 30,000 (UK), 106 of 30,001 (Germany), 87 of 30,000 (France), 31 of 12,011 (Spain), 22 of 17,500 (Italy), and 34 of 24,000 (Brazil). Persistent seizures (≥1 per year) were reported in over 40% of patients with IGE (10-15% with ≥1 seizure per week, 10-15% with 1-3 seizures per month, 20-25% with 1-4 seizures per year). Over 75% were treated with antiepileptic drugs (AEDs). Compared with those having <1 seizure per year (reference group), patients in the two most frequent seizure categories reported worse MCS and PCS scores. Patients in the three highest seizure frequency groups consistently reported worse health utility scores, and greater presenteeism (attending work while not physically or mentally capable of working), overall work impairment, activity impairment, HRU, indirect costs, and direct costs than the reference group. Despite the availability of AEDs during the year surveyed, a substantial number of patients experienced persistent seizures. Increasing seizure frequency was clearly associated with worse outcomes. The burden of PGTCS and IGE may be proportionally reduced by newer AEDs which may increase the proportion of seizure-free patients or shift more patients into lower seizure frequency categories.

Which children receive vigabatrin? Characteristics of pediatric patients enrolled in the mandatory FDA registry.

Vigabatrin (Sabril®) is an antiepileptic drug (AED) currently indicated in the US as a monotherapy for patients 1month to 2years of age with infantile spasms (IS) and as adjunctive therapy for patients ≥10years of age with refractory complex partial seizures (rCPS) whose seizures have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. The approval required an FDA mandated registry. This article describes 5years of demographic and treatment exposure data from US pediatric patients (<17years). Participation is mandatory for all US Sabril® prescribers and patients. A benefit-risk assessment must be documented for patient progression to maintenance therapy. This includes demographic diagnosis and reports of ophthalmologic assessments (where available). Patient data were grouped by age as proxies for indication (IS: <3years, rCPS: ≥3 to <17years). As of August 26, 2014, 5546/6823 enrolled patients were pediatric/total; 4472 (81%) were vigabatrin-naïve. Seventy-one percent of patients were <3years of age; 29% were ≥3 to <17years of age. Etiologies of IS were identified as cryptogenic (21%), symptomatic tuberous sclerosis (17%), and symptomatic other (42%). The majority of patients with IS (56%) attempted no prior treatments; 16% received adrenocorticotropic hormone prior to vigabatrin. A third of patients with IS were receiving 1 concomitant treatment with vigabatrin. For patients with rCPS, 39% attempted 1-3 prior treatments; 27% were receiving 2 concomitant treatments at enrollment. A total of 1852 (41%) patients did not undergo baseline ophthalmological assessment; 25% of patients with IS and 42% of patients with rCPS were exempted for neurologic disabilities. Kaplan-Meier estimates predict that 71% and 65% of vigabatrin-naïve patients with IS and rCPS, respectively, would remain in the registry at 6months. Most pediatric vigabatrin patients have IS as an underlying diagnosis, especially those <3years of age. A proportion of those with rCPS remain on long-term vigabatrin despite the risk of adverse events.

Sabril® registry 5-year results: Characteristics of adult patients treated with vigabatrin.

Vigabatrin (Sabril®), approved in the US in 2009, is currently indicated as adjunctive therapy for refractory complex partial seizures (rCPS) in patients ≥ 10 years old who have responded inadequately to several alternative treatments and as monotherapy for infantile spasms (IS) in patients 1 month to 2 years of age. Because of reports of vision loss following vigabatrin exposure, FDA approval required a risk evaluation mitigation strategy (REMS) program. Vigabatrin is only available in the US through Support, Help, And Resources for Epilepsy (SHARE), which includes a mandated registry. This article describes 5 years of demographic and treatment exposure data from adult patients (≥ 17 years old) in the US treated with vigabatrin and monitored in the ongoing Sabril® registry. Registry participation is mandatory for all US Sabril® prescribers and patients. A benefit-risk assessment must be documented by the physician for a patient to progress to maintenance therapy, defined as 1 month of vigabatrin treatment for patients with IS and 3 months for patients with rCPS. Ophthalmologic assessments must be documented during and after completion of therapy. As of August 26, 2014, a total of 6823 patients were enrolled in the registry, of which 1200 were adults at enrollment. Of these patients, 1031 (86%) were naïve to vigabatrin. The majority of adult patients (n=783, 65%) had previously been prescribed ≥ 4 AEDs, and 719 (60%) were receiving ≥ 3 concomitant AEDs at vigabatrin initiation. Prescribers submitted an initial ophthalmological assessment form for 863 patients; an ophthalmologic exam was not completed for 300 (35%) patients and thus, were considered exempted from vision testing. Of these patients, 128 (43%) were exempted for neurologic disabilities. Clinicians discontinued treatment in 8 patients because of visual field deficits (VFD) (5 patients naïve to vigabatrin and 3 patients previously exposed). Based on Kaplan-Meier survival estimates, it is estimated that approximately 71%, 55%, and 40% of adult patients naïve to vigabatrin would remain in the registry at 3, 6, and 12 months, respectively. These demographic data suggest that a proportion of adult patients remain on vigabatrin long-term despite the risks of adverse events and significant underlying AED resistance and neurologic disease.

Descriptive epidemiology of epilepsy in the U.S. population: A different approach.

OBJECTIVE: Determine prevalence and incidence of epilepsy within two health insurance claims databases representing large sectors of the U.S. METHODS: A retrospective observational analysis using Commercial Claims and Medicare (CC&M) Supplemental and Medicaid insurance claims data between January 1, 2007 and December 31, 2011. Over 20 million continuously enrolled lives of all ages were included. Our definition of a prevalent case of epilepsy was based on International Classification of Diseases, Ninth Revision, Clinical Modification-coded diagnoses of epilepsy or seizures and evidence of prescribed antiepileptic drugs. Incident cases were identified among prevalent cases continuously enrolled for ≥ 2 years before the year of incidence determination with no epilepsy, seizure diagnoses, or antiepileptic drug prescriptions recorded. RESULTS: During 2010 and 2011, overall age-adjusted prevalence estimate, combining weighted estimates from all datasets, was 8.5 cases of epilepsy/1,000 population. With evaluation of CC&M and Medicaid data separately, age-adjusted prevalence estimates were 5.0 and 34.3/1,000 population, respectively, for the same period. The overall age-adjusted incidence estimate for 2011, combining weighted estimates from all datasets, was 79.1/100,000 population. Age-adjusted incidence estimates from CC&M and Medicaid data were 64.5 and 182.7/100,000 enrollees, respectively. Incidence data should be interpreted with caution due to possible misclassification of some prevalent cases. SIGNIFICANCE: The large number of patients identified as having epilepsy is statistically robust and provides a credible estimate of the prevalence of epilepsy. Our study draws from multiple U.S. population sectors, making it reasonably representative of the U.S.-insured population.