Greater need for treatment optimization in patients with epilepsy initiating adjunctive therapy: Results of a retrospective claims analysis of antiseizure medication drug load in the United States.

BACKGROUND: This retrospective, observational study used US claims data to assess changes in antiseizure medication (ASM) drug load for a cohort of patients with epilepsy. METHODS: Adults (≥18 years) with a diagnosis of epilepsy (ICD-10 code G40.xxx) who started new adjunctive ASM treatment with one of 4 branded (brivaracetam, eslicarbazepine, lacosamide, perampanel) or 4 unbranded (carbamazepine, lamotrigine, levetiracetam, topiramate) ASMs between January 1, 2016 and December 31, 2020 were identified from IBM MarketScan® research databases (primary study population). Patients must have been continuously enrolled 360 days before the start of the new ASM (eligibility period). Follow-up was from the start of new ASM until Day 540 (∼18 months). The primary endpoint was concomitant ASM drug load, which included all ASMs except the new (comparator) ASM. A sensitivity analysis population included adults with epilepsy who were continuously enrolled for ≥ 180 days during at least one calendar year in the study period (2016-2020), whether or not the comparator ASM was new or existing during that period. Total ASM drug load, which included comparator ASM and concomitant ASMs, was assessed in the sensitivity analysis population. RESULTS: In total, 21,332 patients were included in the primary study population, of which 5767 initiated branded ASMs and 15,565 initiated unbranded ASMs. A total of 392,426 patients were included in the sensitivity analysis population during at least one calendar year 2016-2020. Concomitant ASM drug load increased in the 360 days prior to new ASM start and slightly declined thereafter. Mean concomitant ASM drug load for the primary population was 1.6 (SD 1.8) at new ASM start. Concomitant drug load was higher among those starting branded ASM comparators compared to those starting unbranded comparators. Mean total ASM drug load for patients increased over time and was approximately double for patients exposed to branded ASMs (mean range 2.1 to 2.7) compared to that of patients exposed to any unbranded ASM (mean range 1.0 to 1.3). CONCLUSION: Concomitant ASM drug load increased prior to addition of new ASM, with higher increases observed among patients starting branded vs unbranded ASMs, followed by slight decreases thereafter. Total drug load increased linearly among all patients. These findings underscore the need for ongoing ASM regimen evaluation and treatment optimization in patients with epilepsy.

Healthcare resource utilization and costs before and after lacosamide initiation as adjunctive therapy among patients with epilepsy in the United States.

OBJECTIVE: The objective of this study was to evaluate all-cause and epilepsy-specific healthcare resource utilization and costs following lacosamide (LCM) initiation as adjunctive therapy for the treatment of epilepsy. METHODS: A noninterventional retrospective database analysis was conducted that examined patients diagnosed as having epilepsy who added LCM to existing antiepileptic drug (AED) therapy between 2009 and 2016 (the first LCM prescription was the index event). This study used a single-case design whereby patients served as their own controls. Patients were further required to have a minimum of 12 months of continuous eligibility before (preindex period) and after (postindex period) their index event. In the 12-month postindex period, the only allowed AED regimen change was the addition of LCM. Demographic and clinical characteristics were measured at index and during the preindex period, respectively. All-cause and epilepsy-specific healthcare resource utilization and costs were measured and compared in the pre- and postindex periods. Paired t- and McNemar's tests were conducted to assess the significant differences between pre- and postindex. Univariate analyses were used to analyze the impact of LCM on specific subpopulations. RESULTS: The study sample comprised of 2171 patients: mean (standard deviation [SD]) age: 38.9 (19.3) years; 52.6% female. Just over half (56%) of these patients were on monotherapy before adding LCM. Prior to adding LCM, 28.8% of patients had an epilepsy-specific inpatient (IP) admission, and 35.7% of patients had an all-cause IP admission, compared with 18.2% and 26.1% of patients in the post-LCM period, respectively (both p < 0.0001). Likewise, 35.6% of patients had an epilepsy-specific emergency room (ER) visit, and 50.0% had an all-cause ER visit prior to adding LCM, compared with 23.8% and 42.1% in post-LCM, respectively (both p < 0.0001). After adding LCM, one-year mean [SD] epilepsy-specific IP admission costs decreased by 42.9% ($13,647 [$52,290] to $7788 [$32,321]), and all-cause IP admission costs decreased by 38.6% ($20,654 [$72,716] to $12,688 [$46,120]) (both p < 0.0001). One-year epilepsy-specific mean [SD] ER costs decreased by 35.2% ($691 [$1756] to $448 [$1909]; p < 0.0001), and all-cause ER cost decreased by 17.8% ($1217 [$3014] to $1000 [$2970]; p < 0.01). CONCLUSIONS: Epilepsy-related IP hospitalizations and ER visits (indicators of seizures) were significantly reduced in patients with epilepsy 12 months after adding LCM as an adjunctive therapy to existing AED treatment in a real-world setting, leading to reduced healthcare resource utilization and epilepsy costs.

Indications and methodology for video-electroencephalographic studies in the epilepsy monitoring unit.

Although the epilepsy and neurology communities have position papers on a number of topics pertaining to epilepsy diagnosis and management, no current paper exists for the rationale and appropriate indications for epilepsy monitoring unit (EMU) evaluation. General neurologists, hospital administrators, and insurers also have yet to fully understand the role this type of testing has in the diagnosis and management of individuals with paroxysmal neurologic symptoms. This review outlines the indications for long-term video-electroencephalography (VEEG) for typical elective admissions to a specialized inpatient setting. The common techniques used in EMUs to obtain diagnostic information are reviewed. The added benefit of safety measures and clinical testing above that available for routine or long-term ambulatory electroencephalography is also discussed. The indications for admission to the EMU include differential diagnosis of paroxysmal spells, characterization of seizure types, presurgical epilepsy evaluations, seizure quantification, monitoring medication adjustment in a safe setting, and differentiation between seizures and side effects. We conclude that the appropriate use of this specialized testing can lead to an early and correct diagnosis in a variety of clinical circumstances. The EMU evaluation is considered the gold standard test for the definitive diagnosis of epilepsy and seizure-like spells.

Economic impact of epilepsy and the cost of nonadherence to antiepileptic drugs in older Medicare beneficiaries.

Epilepsy is most prevalent among older individuals, and its economic impact is substantial. The development of economic burden estimates that account for known confounders, and using percent incremental costs may provide meaningful comparison across time and different health systems. The first objective of the current study was to estimate the percent incremental healthcare costs and the odds ratio (OR) for inpatient utilization for older Medicare beneficiaries with epilepsy and without epilepsy. The second objective was to estimate the percent incremental healthcare costs and the OR for inpatient utilization associated with antiepileptic drug (AED) nonadherence among Medicare beneficiaries with epilepsy. The OR of inpatient utilization for cases compared with controls (i.e., non-cases) were 2.4 (95% CI 2.3 to 2.6, p-value<0.0001) for prevalent epilepsy and 3.6 (95% CI 3.2 to 4.0, p-value<0.0001) for incident epilepsy. With respect to total health care costs, prevalent cases incurred 61.8% (95% CI 56.6 to 67.1%, p-value<0.0001) higher costs than controls while incident cases incurred 71.2% (95% CI 63.2 to 79.5%, p-value <0.0001) higher costs than controls. The nonadherence rates were 33.6 and 32.9% for prevalent and incident cases, respectively. Compared to nonadherent cases, the OR of inpatient utilization for adherent prevalent cases was 0.66 (95% CI 0.55 to 0.81, p-value <0.0001). The cost saving for a prevalent case adherent to AEDs was 13.2% (95% CI 6.6 to 19.4%, p-value=0.0001) compared to a nonadherent case. An incident case adherent to AEDs spent 16.4% (95% CI 6.5 to 25.2%, p-value=0.002) less than a nonadherent incident case on health care. Epilepsy is associated with higher health care costs and utilization. Older Medicare beneficiaries with epilepsy incur higher total health care spending and have higher inpatient utilization than those without epilepsy. Total health care spending is less for older Medicare beneficiaries who have prevalent or incident epilepsy if they are adherent to AEDs.

Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy.

Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of <0.05. Four genes and seven RNA probes were with prognostic value for post-operative seizure-free outcome. Gene expression associated with seizure-free outcome included relative down-regulation of zinc finger protein 852 (ZNF852), CUB domain-containing protein 2 (CDCP2), proline-rich transmembrane protein 1 (PRRT1), hypothetical LOC440200 (FLJ41170), RNA probe 8047763, RNA probe 8126238, RNA probe 8113489, RNA probe 8092883, RNA probe 7935228, RNA probe 806293, and RNA probe 8104131. This study describes the predictive value of temporal cortical gene expression for seizure-free outcome after ATL/AH. Four genes and seven RNA probes were found to predict post-operative seizure-free outcome. Future prospective investigation of these genes and probes in human brain tissue and blood could establish new biomarkers predictive of seizure outcome following ATL/AH.

Felt and enacted stigma in elderly persons with epilepsy: A qualitative approach.

Stigma is a common psychological consequence of chronic diseases, including epilepsy; however, little research has been done to determine the effect of stigma on persons with epilepsy, especially the elderly. We interviewed 57 older adults with epilepsy to discover the extent and consequences of, and reasons for, epilepsy-related stigma in their lives. Felt stigma was more frequently reported than enacted stigma, with over 70% having experienced this form of stigma. Participants described ignorance and fear of the disease as the foundation of epilepsy-related stigma. The most common response to stigmatizing events was a decrease in epilepsy disclosure to family or friends. Results from this study could inform interventions designed for elderly persons with epilepsy and their support networks, as well as educational campaigns for the general public.

Cortical gene expression correlates of temporal lobe epileptogenicity.

INTRODUCTION: Despite being one of the most common neurological diseases, it is unknown whether there may be a genetic basis to temporal lobe epilepsy (TLE). Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between TLE patients with high vs. low baseline seizure frequency. METHODS: Baseline seizure frequency was used as a clinical measure of epileptogenicity. Twenty-four patients in high or low seizure frequency groups (median seizures/month) underwent anterior temporal lobectomy with amygdalohippocampectomy for intractable TLE. RNA was isolated from the lateral temporal cortex and submitted for expression analysis. Genes significantly associated with baseline seizure frequency on likelihood ratio test were identified based on >0.90 area under the ROC curve, P value of <0.05. RESULTS: Expression levels of forty genes were significantly associated with baseline seizure frequency. Of the seven most significant, four have been linked to other neurologic diseases. Expression levels associated with high seizure frequency included low expression of Homeobox A10, Forkhead box A2, Lymphoblastic leukemia derived sequence 1, HGF activator, Kelch repeat and BTB (POZ) domain containing 11, Thanatos-associated protein domain containing 8 and Heparin sulfate (glucosamine) 3-O-sulfotransferase 3A1. CONCLUSIONS: This study describes novel associations between forty known genes and a clinical marker of epileptogenicity, baseline seizure frequency. Four of the seven discussed have been previously related to other neurologic diseases. Future investigation of these genes could establish new biomarkers for predicting epileptogenicity, and could have significant implications for diagnosis and management of temporal lobe epilepsy, as well as epilepsy pathogenesis.

Healthcare utilization of patients with epilepsy in Yuma County, Arizona: do disparities exist?

The aim of this study was to describe the disparities in healthcare utilization and costs between Hispanic and non-Hispanic patients with seizures or epilepsy. We reviewed the insurance status and healthcare resource utilization data from 2005 to 2008 for all patients with seizures and epilepsy seen at the Yuma Regional Medical Center (YRMC). Charges for medical services provided to Hispanic patients with epilepsy between the ages of 18 and 49 were significantly less than those for non-Hispanic patients with epilepsy (Hispanic: $3167.63 versus non-Hispanic: $5154.36, P<0.001). Taking into account the differences in insurance status, setting of care, and total number of procedures, we still saw a significant difference in charges between the two groups at the outpatient settings. These data differ from currently available data on national and Eastern US Hispanic patients with epilepsy, suggesting that patients in this border community are somehow different from Hispanics elsewhere in the US.

Emergency department care of seizure patients: demographic trends in southern Arizona.

The aim of this study was to describe the epidemiology of epilepsy and characteristics of patients with seizures who presented at the Yuma Regional Medical Center Emergency Department (YRMC ED) from 2005 to 2008. A seizure diagnosis was present in 2.7% of the patients, and accounted for 1.7% of all ED visits. Visits by patients identified as having epilepsy accounted for 0.3% of all ED visits. Patients with seizures were 2.8 times more likely to have used the ED for 2 or more years of the study period compared with control patients. Patients with at least one ED visit because of seizures were more likely to have multiyear visits, 43.6% visiting the ED within 2 or more years. Patients with epilepsy and seizures were significantly younger than the no-seizure control group. Patients who had ever been admitted to the ED for seizures or epilepsy had higher ED utilization even if the subsequent admissions were not seizure related.

More effective assessment of adverse effects and comorbidities in epilepsy: results of a Phase II communication study.

Research was conducted to evaluate conversations about epilepsy between community-based neurologists and patients. Adverse effects of antiepileptic drugs and mood/behavioral issues were infrequently discussed, and neurologists and patients disagreed about these issues postvisit. Follow-up research was conducted to assess the impact of a previsit assessment tool on discussions of epilepsy. Twenty neurologists reviewed a tool incorporating questions from validated instruments (Adverse Events Profile [AEP] and Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]). Naturally occurring interactions between neurologists and 60 patients were recorded. Neurologists and patients were interviewed separately. All components were transcribed and analyzed using sociolinguistics. Using the previsit assessment tool increased the number of discussions about adverse effects and mood/behavioral issues and increased neurologist-patient agreement about issues postvisit. Visit length did not increase significantly when the tool was used. Ten months after follow-up research, 50% of neurologists reported continuing to use the tool in everyday practice with patients with epilepsy.

Accreditation of Epilepsy Centers.

In 2012, the Institute of Medicine recommended that a formal process be developed for the accreditation of epilepsy centers in the United States. This article provides some of the background and processes that led to the criteria by which epilepsy centers are now accredited.

Essential services, personnel, and facilities in specialized epilepsy centers--revised 2010 guidelines.

This document was developed by the members of the Committee to Revise the Guidelines for Services, Personnel, and Facilities at Specialized Epilepsy Centers. After discussions with the general membership they were adopted by the Board of the National Association of Epilepsy Centers. The Guidelines will be reviewed and updated when considered necessary by the Board.

Behavioral risk factors among Arizonans with epilepsy: Behavioral Risk Factor Surveillance System 2005/2006.

Modifiable risk factors to help improve health outcomes for people with epilepsy in Arizona were identified using the 2005-2006 Arizona Behavioral Risk Factor Surveillance System (BRFSS). Of 9524 adults who participated in this survey, 125 reported ever being diagnosed with epilepsy (lifetime prevalence=1.3%, 95% CI=1.1-1.6%). Individuals with active epilepsy (those who had seizures in the prior 3 months and/or were taking anticonvulsants) had an overall lower quality of life. This likely resulted from a large number of medical comorbidities and poor mental and physical health days. Regression models suggested that for individuals with active epilepsy, physical activity was associated with fewer activity-limited days, whereas for individuals with inactive epilepsy, medical comorbidity was positively associated with activity-limited days. Further research is needed to increase the reliability of the findings.

Economic burden associated with the use of generic antiepileptic drugs in the United States.

This study quantifies the economic burden associated with generic-versus-branded use of antiepileptic drugs (AEDs) in the United States. Adult patients with epilepsy receiving carbamazepine, gabapentin, phenytoin, primidone, or zonisamide were selected from the PharMetrics database. By use of an open-cohort design, patients were classified into mutually exclusive periods of generic-versus-branded AED use. Annualized cost differences (CDs) between periods were estimated using multivariate regressions. Results were stratified into stable versus unstable epilepsy and newer-generation versus older-generation AEDs. A total of 33,625 patients (52% male, mean age=51 years) were observed. Periods of generic AED treatment were associated with higher medical service costs (adjusted CD [95% CI]=$3186 [$2359; $4012]), stable pharmacy costs ($69 [$-34; $171]), and greater total costs ($3254 [$2403; $4105]) versus brand use. Epilepsy-related costs represented 30% of incremental costs. Similar findings were observed for patients with stable and unstable epilepsy and users of newer-generation and older-generation AEDs. Significantly higher health care costs were observed during generic AED use across seizure control and AED subgroups.

Effects of lamotrigine compared with levetiracetam on anger, hostility, and total mood in patients with partial epilepsy.

PURPOSE: To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures. METHODS: This randomized, double-blind, parallel-group study in adults with partial seizures included an 8-week escalation phase, during which adjunctive lamotrigine (n = 132) or adjunctive levetiracetam (n = 136) was titrated to a target dose, and a 12-week, double-blind maintenance phase, during which dosages of study medication and concomitant antiepileptic drugs were maintained. The primary endpoint was change from baseline to the end of the maintenance phase (week 20) in the Anger-Hostility subscale score of the Profile of Mood States (POMS). RESULTS: Improvement with lamotrigine relative to levetiracetam was observed for mean +/- SD (standard deviation) change from baseline to the end of the maintenance phase (week 20) on the Anger-Hostility subscale (lamotrigine -2.0 +/- 8.2, levetiracetam -0.3 +/- 8.4; p = 0.024) (the primary endpoint); the Anger-Hostility subscale on weeks 5, 6, 7, 8, 9, 11, 12, 14, 16, 18, and 19; and the Total Mood Disturbance score on weeks 6, 7, 8, 9, 11, 12, 17, 19, and 20. Improvement (p < 0.05) with lamotrigine relative to levetiracetam was also observed on the POMS subscales Depression-Dejection, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. No difference in seizure frequency was observed between groups. The most common adverse events with both medications were headache and dizziness. DISCUSSION: Adjunctive lamotrigine significantly improved Anger-Hostility subscale scores relative to adjunctive levetiracetam in patients with partial seizures at the end of 20 weeks. This difference was consistently observed throughout the treatment period. Similar improvement with lamotrigine versus levetiracetam was observed for other mood symptoms.

Conversations between community-based neurologists and patients with epilepsy: results of an observational linguistic study.

An in-office linguistic study was conducted to assess neurologist-patient discussions of epilepsy. Naturally occurring interactions among 20 neurologists and 60 of their patients with epilepsy were recorded. Participants were interviewed separately postvisit. Transcripts were analyzed using sociolinguistic techniques. Of 59 patients taking antiepileptic drugs previsit, 44 (75%) discussed side effects with their neurologist. Side effect discussions were most often neurologist initiated. Postvisit, patients and neurologists often disagreed about which side effects were experienced. The presence of a caregiver (e.g., spouse) usually resulted in lengthier, more detailed discussions of side effects, without drastically increasing overall visit length. Discussions of mood- and behavior-related comorbidities occurred infrequently (14 of 60 visits); postvisit, neurologists stated that they felt that management of these conditions was outside their area of expertise. Communication gaps observed in discussions of epilepsy and its treatment warrant further exploration. Additional research is currently underway to assess the efficacy of a previsit assessment tool.

Leukocyte expression profiles reveal gene sets with prognostic value for seizure-free outcome following stereotactic laser amygdalohippocampotomy.

Among patients with intractable epilepsy, the most commonly performed surgical procedure is craniotomy for amygdalohippocampectomy (AH). Stereotactic laser amygdalohippocampotomy (SLAH) has also been recently employed as a minimally invasive treatment for intractable temporal lobe epilepsy (TLE). Among patients treated with AH and SLAH approximately 65% and 54% of patients become seizure-free, respectively. Therefore, selection criteria for surgical candidates with improved prognostic value for post-operative seizure-free outcome are greatly needed. In this study, we perform RNA sequencing (RNA-Seq) on whole blood leukocyte samples taken from 16 patients with intractable TLE prior to SLAH to test the hypothesis that pre-operative leukocyte RNA expression profiles are prognostic for post-operative seizure outcome. Multidimensional scaling analysis of the RNA expression data indicated separate clustering of patients with seizure free (SF) and non-seizure-free (NSF) outcomes. Differential expression (DE) analysis performed on SF versus NSF groups revealed 24 significantly differentially expressed genes (≥2.0-fold change, p-value < 0.05, FDR <0.05). Network and pathway analyses identified differential activation of pathways involved in lipid metabolism, morphology of oligodendrocytes, inflammatory response, and development of astrocytes. These results suggest that pre-operative leukocyte expression profiles have prognostic value for seizure outcome following SLAH.

Altered expression of signaling pathways regulating neuronal excitability in hippocampal tissue of temporal lobe epilepsy patients with low and high seizure frequency.

Despite recent advances in our understanding of synaptic transmission associated with epileptogenesis, the molecular mechanisms that control seizure frequency in patients with temporal lobe epilepsy (TLE) remain obscure. RNA-Seq was performed on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. Differential expression (DE) analysis of individuals with low (LSF, mean = 4 seizure/month) versus high (HSF, mean = 60 seizures/month) seizure frequency identified 979 genes with ≥2-fold change in transcript abundance (FDR-adjusted p-value ö0.05). Comparisons with post-mortem controls revealed a large number of downregulated genes in the HSF (1676) versus LSF (399) groups. More than 50 signaling pathways were inferred to be deactivated or activated, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both groups, key neuronal system pathways were systematically deactivated in the HSF group, including calcium, CREB and Opioid signaling. We also infer that enhanced expression of a signaling cascade promoting synaptic downscaling may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE.

An update on the prevalence and incidence of epilepsy among older adults.

OBJECTIVE: To estimate the prevalence and incidence of epilepsy among beneficiaries of Arizona Medicare aged 65 and over. METHODS: An analysis of Medicare administrative claims data for 2009-2011 for the State of Arizona was conducted. Epilepsy was defined as a beneficiary who had either≥one claim with diagnostic code of 345.xx (epilepsy) or at least two claims with diagnosis code of 780.3x (seizure) ≥30days apart. Stroke-related and psychiatric comorbidities were determined by diagnostic codes. Average annual prevalence and incidence were calculated and stratified by demographic characteristics and comorbidities. Odds ratios (OR) and 95% confidence intervals (CI) were calculated as measures of effect for prevalence and incidence and the chi-square statistic was calculated to compare the proportions of epilepsy cases with and without comorbidities (alpha=0.05). RESULTS: The overall average annual prevalence and incidence over the study period was 15.2/1000 and 6.1/1000, respectively. Relative to the 65-69 age group and White beneficiaries, the highest prevalence was observed for beneficiaries 85 years or older (19.8/1000, OR 1.66, 95% CI 1.53-1.81) and Native Americans (21.2/1000, OR 1.42, 95% CI 1.25-1.62). In contrast, the highest incidence rates were observed for beneficiaries 85 years and older (8.5/1000, OR 1.82, 95% CI 1.60-2.07) and for Black beneficiaries (8.7/1000, OR 1.44, 95% CI 1.12-1.86). The incidence rate for Native Americans was not significantly different from that for White beneficiaries (6.2/1000, OR 1.02, 95% CI 0.81-1.29). More than one quarter of all cases (25.7%) and 31% of incident cases had either stroke-related and/or psychiatric comorbidities (all p-values < 0.001). CONCLUSIONS: Epilepsy is a significant neurological disease among Medicare beneficiaries 65 years and older. Beneficiaries aged 85 and older and Black and Native Americans experienced higher rates of epilepsy than other demographic subgroups compared to White beneficiaries.

Cost sharing for antiepileptic drugs: medication utilization and health plan costs.

OBJECTIVES: To examine the association between health plan out-of-pocket (OOP) costs for antiepileptic drugs and healthcare utilization (HCU) and overall plan spending among US-based commercial health plan beneficiaries with epilepsy. STUDY DESIGN: Retrospective cohort. METHODS: The Truven MarketScan Commercial Claims database for January 1, 2009, to June 30, 2015, was used. Patients 65 years or younger with epilepsy and at least 12 months of continuous enrollment before index (date meeting first epilepsy diagnostic criteria) were included. Analyses were adjusted for age group, gender, beneficiary relationship, insurance plan type, and Charlson Comorbidity Index score. Primary outcomes included proportion of days covered (PDC), HCU, and healthcare spending in 90-day postindex periods. Associations between OOP costs and mean PDC, HCU, and plan healthcare spending per 90-day period were estimated. RESULTS: Across 5159 plans, 187,241 beneficiaries met eligibility criteria; 54.3% were female, 41.7% were aged 45 to 65 years, and 62.4% were in preferred provider organization plans. Across postindex 90-day periods, mean (SD) PDC, epilepsy-specific hospitalizations, outpatient visits, and emergency department visits were 0.85 (0.26), 0.02 (0.13), 0.34 (0.47), and 0.05 (0.22), respectively. Median (interquartile range) spending per 90-day period was $1488 ($459-$4705); median epilepsy-specific spending was $139 ($18-$623). Multivariable linear regression without health plan fixed effects revealed that higher OOP spending was associated with a decrease in PDC (coefficient, -0.008; 95% CI, -0.009 to -0.006; P <.001) and an increase in overall spending (218.6; 95% CI, 47.9-389.2; P = .012). Health plan fixed effects model estimates were similar, except for epilepsy-specific spending, which was significant (120.6; 95% CI, 29.2-211.9; P = .010). CONCLUSIONS: Increases in beneficiaries' OOP costs led to higher overall spending and lower PDC.