Linda Kalilani

Comparing the incidence of falls/fractures in Parkinson's disease patients in the US population

Patients with Parkinson’s disease (PD) may experience falls and/or fractures as a result of disease symptoms. There are limited data available from long-term studies estimating the incidence of falls/fractures in patients with PD. The objective was to compare the incidence rate of falls/fractures in PD patients with non-PD patients in a US population. This was a retrospective study using a US-based claims database (Truven Health MarketScan®) that compared the incidence rate of falls/fractures in PD subjects with non-PD subjects. The study period included the 12 months prior to index date (defined as earliest PD diagnosis [International Classification of Diseases, Ninth Revision, Clinical Modification code 332.0]) and a postindex period to the end of data availability. Fractures were defined by inpatient/outpatient claims as a principal or secondary diagnosis and accompanying procedure codes during the postindex period. Incidence rates and 95% CIs for falls/fractures were calculated as the number of events per 10,000 person-years of follow-up using negative binomial or Poisson regression models. Twenty-eight thousand two hundred and eighty PD subjects were matched to non-PD subjects for the analysis (mean [SD] age, 71.4 [11.8] years; 53% male). A higher incidence rate (adjusted for comorbidities and medications) of all fall/fracture cases and by fall and fracture types was observed for PD subjects versus non-PD subjects; the overall adjusted incidence rate ratio comparing PD to non-PD subjects was 2.05; 95% CI, 1.88–2.24. The incidence rate of falls/fractures was significantly higher in subjects with PD compared with non-PD subjects in a US population.

Lacosamide and concomitant use of antiepileptic and other medications in a US population — A retrospective cohort study ☆

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.

Antiepileptic Drug Titration and Related Health Care Resource Use and Costs

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

Characterizing Subpopulations with Better Response to Treatment Using Observational Data - an Epilepsy Case Study

80.48 to

Current state of the union of epilepsy care in the United States: Antiepileptic drugs — An introduction to the Connectors Project

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.

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

Electronic health records and health insurance claims, providing observational data on millions of patients, offer great opportunities, and challenges, for population health studies. The objective of this study is identifying subpopulations that are likely to benefit from a given treatment using observational data. We refer to these subpopulations as “better responders” and focus on characterizing these using linear scores with a limited number of variables. Building upon well-established causal inference techniques for analyzing observational data, we propose two algorithms that generate such scores for identifying better responders, as well as methods for evaluating and comparing these scores. We applied our methodology to a large dataset of ~135,000 epilepsy patients derived from claims data. Out of this sample, 85,000 were used to characterize subpopulations with better response to next-generation (“Newer”) anti-epileptic drugs (AEDs), compared to an alternative treatment by first-generation (“Older”) AEDs. The remaining 50,000 epilepsy patients were then used to evaluate our scores. Our results demonstrate the ability of our scores to identify large subpopulations of epilepsy patients with significantly better response to newer AEDs.

The challenges of assessing effectiveness of lacosamide using electronic medical record databases

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.

Comparing the healthcare utilization and direct medical costs in newly diagnosed epilepsy patients and a comparator non-epilepsy population: a US database analysis (S34.002)

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.