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Objective: To examine the factors and reasons influencing treatment initiation decisions in patients with newly diagnosed epilepsy., Methods: We assessed antiseizure medication initiation decisions in adults with newly diagnosed epilepsy seen at first seizure clinics in Western Australia between 1999 and 2016 and followed to 2018., Results: Of 610 patients (median age 40 years, 61.0% male), 426 (69.8%) were diagnosed after two or more seizures and 184 (30.2%) after a single seizure with risk factors for recurrence. Treatment was commenced in 427 patients (70.0%) at diagnosis, 112 (18.4%) during follow-up, mostly after further seizures, whereas 71 (11.6%) remained untreated at last follow-up. Elders (≥65 years, odds ratio [OR] = 3.06, 95% confidence interval [CI]: 1.62-5.80), more seizures (OR = 3.48, 95% CI: 2.03-5.96), and epileptogenic lesions on neuroimaging (OR = 2.15, 95% CI: 1.26-3.68) had a higher likelihood of treatment at diagnosis. Patients with less than one seizure per year within the preceding year (OR = 0.40, 95% CI: 0.21-0.73) and of higher socioeconomic status (OR = 0.985, 95% CI: 0.977-0.994) were less likely to be treated. For 93 patients (15.2%), treatment was not recommended at diagnosis, most commonly because only a single seizure had occurred. Ninety patients (14.8%) declined recommended treatment, mostly because they were unconvinced of the need for treatment or the diagnosis., Significance: Thirty percent of adults with newly diagnosed epilepsy were not immediately treated. Treatment initiation in this real-world cohort was influenced by age, number of seizures prior to diagnosis, imaging findings, patient preferences, and socioeconomic status., (Wiley Periodicals, Inc. © 2020 International League Against Epilepsy.)

Purpose: Describe treatment patterns in patients from the United States with new-onset epilepsy, comparing those with and without lesional epilepsy., Methods: In this observational study we used Truven Health MarketScan databases derived from commercial health insurance, Medicare and Medicaid claims covering at least 5 years, commencing in 2008. We identified incident epilepsy cases based on International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating epilepsy or recurrent seizures, taking into account antiepileptic drug (AED) claims, consistent with International League Against Epilepsy Commission on Epidemiology recommendations. We identified patients with lesional epilepsy when associated diagnoses indicated central nervous system infection, neoplasm, traumatic brain injury, stroke, senile dementia and static encephalopathy. Lesional and nonlesional cohorts were matched 1:1 on baseline characteristics of age, sex and insurance type for group comparisons., Results: In unmatched cohorts lesional epilepsy patients (N = 15,302) were more commonly older (mean age 48.7 years) compared with nonlesional epilepsy patients (N = 15,970; mean age 18.5 years). Among lesional patients <20 years of age, the leading putative etiology was static encephalopathy, while among ages ≥20 years and older, the leading putative etiology was stroke or cerebrovascular disease. In matched cohorts (7063 patients each), those with lesional epilepsy were significantly less likely to be untreated at 1 year versus those with nonlesional epilepsy (37.2% vs 56.1%). In children and adults among matched cohorts, levetiracetam was the most common AED prescribed for initial AED therapy for the lesional (39.5%) and nonlesional (32.1%) groups. Lesional epilepsy patients on monotherapy were only slightly less likely than nonlesional epilepsy patients to be on the same AED 1 year after treatment initiation (55.6% vs 59.7%)., Significance: Compared with patients with lesional epilepsy, a higher proportion of patients with nonlesional epilepsy remain untreated 1 year after diagnosis. There were differences in AED selection by epilepsy etiology; levetiracetam is the most commonly prescribed drug for both cohorts., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to describe antiepileptic drug (AED) treatment patterns in patients with epilepsy, with and without psychiatric comorbidities., Methods: This was a retrospective claims-based cohort study using Truven Health MarketScan databases (Commercial and supplemental Medicare, calendar years 2012-2017; Medicaid, 2012-2016). Persons met epilepsy diagnostic criteria, had an index date (first epilepsy diagnosis) with a preceding 2-year baseline (<1 year for persons of 1 to <2 years of age; none for persons <1 year), and continuous medical and pharmacy enrolment without epilepsy/seizure diagnosis or AED prescription during baseline. Based on presence/absence of psychiatric diagnosis codes in the baseline period, persons were classified into two cohorts: with or without psychiatric comorbidities. Outcomes included percentage of treated persons (AED prescription), type, duration, and outcome of first-line AED treatment., Results: There were 18,062 persons in each cohort with and without psychiatric comorbidities, matched by age, sex, and insurance type, who met selection (or inclusion) criteria. More patients with psychiatric comorbidities were prescribed an AED after diagnosis (57.6% vs. 52.8%), and had at least two AEDs prescribed during follow-up (16.7% vs. 11.4%) than patients without psychiatric comorbidities. Most patients with and without psychiatric comorbidities prescribed AED monotherapy as first-line treatment (73.0% vs. 78.7%). Levetiracetam was the most common AED prescribed less frequently in patients with than without psychiatric comorbidities (40.8% vs. 56.7%). More patients with psychiatric comorbidities changed first-line AED treatment than patients without psychiatric comorbidities., Conclusion: The presence of psychiatric comorbidities may impact treatment decisions in newly diagnosed persons with epilepsy to optimize patient outcomes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Extrapolation of efficacy data from adults to children is accepted for focal epilepsy - the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear., Objectives: To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy., Design, Setting, and Participants: A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018., Exposures: Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared., Main Outcomes and Measures: Antiepileptic drug treatment pattern according to seizure type and comorbidities., Results: Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%])., Conclusions and Relevance: Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Objective: To estimate the treatment gap between a new epilepsy diagnosis and antiepileptic drug (AED) initiation in the United States., Methods: Retrospective claims-based cohort study using Truven Health MarketScan databases (commercial and supplemental Medicare, calendar years 2010-2015; Medicaid, 2010-2014) and a validation study using PharMetrics Plus Database linked to LRx claims database (2009-2014). Persons met epilepsy diagnostic criteria, had an index date (first epilepsy diagnosis) with a preceding 2-year baseline (1 year for persons aged 1 to <2 years; none for persons <1 year), and continuous medical and pharmacy enrollment without epilepsy/seizure diagnosis or AED prescription during baseline. Outcomes included percentage of untreated persons (no AED prescription) up to 3 years' follow-up and comparative outcomes (incidence rate ratio: untreated persons/treated persons), including medical events and health care resource utilization., Results: In the primary study, 59,970 persons met selection (or inclusion) criteria; 36.7% of persons with newly diagnosed epilepsy remained untreated up to 3 years after diagnosis. In the validation study (N = 30,890), 31.8% of persons remained untreated up to 3 years after diagnosis. Lack of AED treatment was associated with an adjusted incidence rate ratio (95% confidence interval) of 1.2 (1.2-1.3) for medical events, 2.3 (2.2-2.3) for hospitalizations, and 2.8 (2.7-2.9) for emergency department visits., Conclusions: One-third of newly diagnosed persons remain untreated up to 3 years after epilepsy diagnosis. The increased risk of medical events and health care utilization highlights the consequences of delayed treatment after epilepsy diagnosis, which might be preventable., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Unexpected breakthrough seizures resulting from suboptimal antiepileptic drug (AED) dosing during the titration period, as well as adverse events resulting from rapid AED titration, may influence the titration schedule and significantly increase health care resource use (HRU) and health care costs., Objective: To assess the relationship between AEDs, HRU, and costs during AED titration and maintenance., Methods: Practicing neurologists were recruited from a nationwide panel to provide up to 3 patient records each for this retrospective medical chart review. Patients with epilepsy who were aged ≥ 18 years and had initiated an AED between January 1, 2014, and January 1, 2016, were followed for 6 months from AED initiation. Titration duration was the time from AED initiation to the beginning of treatment maintenance as determined by the physician. Outcomes were epilepsy-specific HRU (hospitalizations, emergency department visits, outpatient visits, physician referral, laboratory testing/diagnostic imaging, and phone calls) and related costs that occurred during the titration or maintenance treatment periods., Results: Of 811 patients, 156, 128, 125, 120, 114, 107, and 61 initiated the following AEDs: levetiracetam, lamotrigine, lacosamide, valproate, topiramate, carbamazepine, and phenytoin, respectively. Most patients (619/803 [77.1%] with complete AED data) received monotherapy. Baseline characteristics were similar across AEDs (mean [SD] age, 36.6 [14.4] years; 59.0% male). Kaplan-Meier estimates of titration duration ranged from 3.3 weeks (phenytoin) to 8.1 weeks (lamotrigine). From titration to maintenance, the overall incidence of HRU per person-month decreased 54.5%-89.3% for each HRU measure except outpatient visits (24.6% decrease). Total epilepsy-related costs decreased from $80.48 to $42.77 per person-month, or 46.9% from titration to maintenance., Conclusions: AED titration periods had higher HRU rates and costs than AED maintenance, suggesting that use of AEDs with shorter titration requirements reduces health care costs, although disease severity may also factor into overall cost., Disclosures: UCB Pharma sponsored this study and reviewed the manuscript. Fishman and Kalilani are employees of UCB Pharma. Wild was an employee of UCB Pharma at the time this analysis was conducted. Song and Swallow are employees of Analysis Group, which received funding from UCB Pharma.

Purpose: Electronic health record (EHR) databases are a potential source for conducting research to generate real world evidence on patient outcomes. The objective of the study was to evaluate the feasibility of using EHR data to assess seizure outcomes in patients treated with lacosamide (LCM) monotherapy., Methods: This was a retrospective cohort study conducted using the Optum clinical EHR database. The study sample comprised patients ≥17 years of age with epilepsy or seizures and treated with LCM monotherapy between 1 January 2009 and 31 December 2013. Structured and unstructured data from prescribed medication and abstracted physician note records were used to identify patients with epilepsy treated with LCM monotherapy and measure seizure frequency outcomes. The index date was the first date of LCM monotherapy, with a 6-month baseline period. Patients were observed for up to 12 months beginning on the index date (follow-up period). The EHR data were not sufficient to compute days supply and explicit duration of LCM and other antiepileptic drug (AED) therapies; therefore, LCM monotherapy was estimated from prescription dates of AEDs. Outcomes were change in seizures per month or change in seizure frequency category from baseline to follow-up. Descriptive statistics were used to describe baseline characteristics and study outcomes., Results: A total of 10,988 patients with at least one LCM prescription were identified during the study period, 470 of whom met all the selection criteria and were included in the study sample. Although many patients had abstracted physician note records that referred to their seizures, only 3.2% of the patients had seizure frequency information that could be used to quantify the number of seizures per month in both the baseline and follow-up periods; thus, this information could not be used to assess the effectiveness of LCM monotherapy on seizure outcomes., Conclusion: Lacosamide monotherapy effectiveness was not estimated because the EHR prescription record data did not have sufficient information on days supply. Additionally, most patients' records did not contain adequate information to allow for evaluation of quantitative changes in seizure frequency based on the number of seizures per month. More studies are needed to validate these study findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: How antiepileptic drugs (AEDs) are used in the United States (US) is one proxy public health indicator for the current state of epilepsy management. The use of phenytoin, other older AEDs, and newer AEDs may act as an indicator for the quality of epilepsy practice in addition to the current American Academy of Neurology quality measures. Data on AED used by states and populations can help identify which public health interventions are necessary to improve the status of epilepsy care. The Connectors Project, a collaboration between the Epilepsy Foundation and UCB Pharma, is a multiyear project designed to improve epilepsy awareness and management in underserved communities. The objective of the first phase of the Connectors Project was to assess geographic variation in epilepsy care and identify locations in need of improved epilepsy care by initially evaluating AED use in the US., Methods: A retrospective cross-sectional administrative claim analysis was conducted using the QuintilesIMS™ database which included US longitudinal retail prescription and office medical claims data. Patients with a confirmed epilepsy diagnosis who were prescribed AEDs were identified. Patients with an AED prescription over a 3-year period from January 2013 to December 2015 were included if they had an epilepsy diagnosis in the 2-year period before their first AED prescription in the reporting period. The percentages of patients initially prescribed phenytoin, other older AEDs (carbamazepine and valproate), and newer AEDs (eslicarbazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, topiramate) were calculated and stratified by US state and Washington, DC. Patients were considered newly treated if they had an epilepsy diagnosis code and had not received an epilepsy drug in the 1-year period preceding the first AED prescription in the reporting period. Data are reported using the moving annual total ending December 2015., Results: Approximately 2.5 million US patients with epilepsy and their AED prescriptions were identified from 2013 to 2015. Predictably, states with the largest population had the highest number of patients with epilepsy who were prescribed an AED, including California, Texas, Florida, and New York. Regions with the highest total proportion of phenytoin use with a low proportion of newer AED use were Mississippi (24.4% and 53.1%, respectively) and Washington, DC (24.7% and 58.1%). Montana had the lowest proportion of phenytoin use with the highest proportion of newer AED use (7.9% and 70.4%). Among newly treated patients (N=237,347), Hawaii (39.1%) and Alaska (38.8%) had the highest percentage of phenytoin use compared with all other states. Idaho (86.1%) and Montana (84.4%) had the highest proportion of newer AED use. Washington, DC (50.9%) and Hawaii (60.9%) had the lowest proportion of patients treated with newer AEDs. North Dakota (29.6%) and Washington, DC (27.9%) had the highest rates of other older AEDs use., Conclusions: A substantial proportion of newly treated US patients with epilepsy are underserved regarding newer AED use with Mississippi and Washington, DC having the highest proportion of phenytoin use relative to newer AED use. Understanding the socioeconomic and demographic barriers for these observations is essential in planning interventions to improve the quality of life and care for patients with epilepsy, including newly treated patients. These data provide a baseline to target educational and clinical interventions for improving the quality of US epilepsy care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Information on the use of lacosamide and concomitant antiepileptic and non-antiepileptic drugs (non-AEDs) is available from clinical trials and observational studies with small sample sizes. This retrospective cohort study was conducted to gain insight into the use of lacosamide in a large number of patients with epilepsy in real-life clinical practice with less restrictive selection criteria compared with clinical trial participants. The Truven Health MarketScan (Commercial Claims and Medicare Supplemental) database was used to identify patients with a prior diagnosis of epilepsy with at least one prescription claim for lacosamide between June 2009 and September 2013 and continuous health insurance enrolment with medical and pharmacy coverage during the 1-year pre-index baseline period. A total of 8859 eligible patients were identified, of whom, at index (lacosamide initiation), 16.8% received lacosamide as monotherapy and 54.0% as polytherapy. The median prescription duration was 196days (Interquartile range 69-476days). Levetiracetam was the most frequently prescribed concomitant AED across all age groups, followed by phenytoin among older (>65years) and lamotrigine among younger patients. Older patients who had LCM monotherapy at initiation, were prescribed fewer concomitant AEDs, but more non-AEDs. The most common non-AED medications were prescribed for pain, psychiatric conditions, hyperlipidemia and gastrointestinal diseases across all age groups. Overall, results suggest that the lacosamide use is driven predominantly by age and that there is substantial use of lacosamide monotherapy (16.8%), despite lack of indication at the time of the study. Results also reveal substantial use of concomitant non-AEDs; 90.4% among patients >65years of age and 54.3% among those ≤17years, confirming the high prevalence of comorbidities among patients with epilepsy across all ages. Despite the availability of numerous newer AEDs, older AEDs are still being frequently prescribed, especially for elderly patients, notably phenytoin. This warrants careful consideration, given the strong propensity of enzyme-inducing AEDs to interact with other drugs, producing unwanted side effects. These results highlight the value of real-life prescription patterns and the potential in informing treatment decisions to ensure patients receive appropriate treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)