Long-term reduction of health care costs and utilization after epilepsy surgery.

OBJECTIVE: To assess long-term direct medical costs, health care utilization, and mortality following resective surgery in persons with uncontrolled epilepsy. METHODS: Retrospective longitudinal cohort study of Medicaid beneficiaries with epilepsy from 2000 to 2008. The study population included 7,835 persons with uncontrolled focal epilepsy ages 18-64 years, with an average follow-up time of 5 years. Of these, 135 received surgery during the study period. To account for selection bias, we used risk-set optimal pairwise matching on a time-varying propensity score, and inverse probability of treatment weighting. Repeated measures generalized linear models were used to model utilization and cost outcomes. Cox proportional hazard was used to model survival. RESULTS: The mean direct medical cost difference between the surgical group and control group was $6,806 after risk-set matching. The incidence rate ratio of inpatient, emergency room, and outpatient utilization was lower among the surgical group in both unadjusted and adjusted analyses. There was no significant difference in mortality after adjustment. Among surgical cases, mean annual costs per subject were on average $6,484 lower, and all utilization measures were lower after surgery compared to before. SIGNIFICANCE: Subjects that underwent epilepsy surgery had lower direct medical care costs and health care utilization. These findings support that epilepsy surgery yields substantial health care cost savings.

Cost-effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: A 5-year follow-up study.

OBJECTIVE: Despite its well-known effectiveness, the cost-effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost-effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy. METHODS: A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed over 5 years in the 15 French centers. Effectiveness was defined as 1 year without a seizure, based on the International League Against Epilepsy (ILAE) classification. Clinical outcomes and direct costs were compared between surgical and medical groups. Long-term direct costs and effectiveness were extrapolated over the patients' lifetimes with a Monte-Carlo simulation using a Markov model, and an incremental cost-effectiveness ratio (ICER) was computed. Indirect costs were also evaluated. RESULTS: Among the 289 enrolled surgery candidates, 207 were operable-119 in the surgical group and 88 in the medical group-65 were not operable and not analyzed here, 7 were finally not eligible, and 10 were not followed. The proportion of patients completely seizure-free during the last 12 months (ILAE class 1) was 69.0% in the operated group and 12.3% in the medical group during the second year (p < 0.001), and it was respectively 76.8% and 21% during the fifth year (p < 0.001). Direct costs became significantly lower in the surgical group the third year after surgery, as a result of less antiepileptic drug use. The value of the discounted ICER was 10,406 (95% confidence interval [CI] 10,182-10,634) at 2 years and 2,630 (CI 95% 2,549-2,713) at 5 years. Surgery became cost-effective between 9 and 10 years after surgery, and even earlier if indirect costs were taken into account as well. SIGNIFICANCE: Our study suggests that in addition to being safe and effective, resective surgery of epilepsy is cost-effective in the medium term. It should therefore be considered earlier in the development of epilepsy.

Retigabine as add-on treatment of refractory epilepsy--a cost-utility study in a Swedish setting.

OBJECTIVES: To calculate comparative incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) and net marginal benefits for retigabine as add-on treatment for patients with uncontrolled focal seizures as compared to add-on lacosamide treatment and no add-on treatment, respectively. MATERIALS & METHODS: Calculations were performed using a validated decision-tree model. The study population consisted of adult patients with focal-onset epilepsy in published randomized placebo-controlled add-on trials of retigabine or lacosamide. Healthcare utilization and QALY for each treatment alternative were calculated. Probabilistic sensitivity analysis was performed using the specification of this model as a basis for Monte Carlo simulations. 2009 prices were used for all costs. RESULTS: Results were reported for a 2-year follow-up period. Retigabine add-on treatment was both more effective and less costly than lacosamide add-on treatment, and the cost per additional QALY for the retigabine no add-on (standard) therapy comparison was estimated at 2009€ 15,753. Using a willingness-to-pay threshold for a QALY of € 50,000, the net marginal values were estimated at 2009€ 605,874 for retigabine vs lacosamide and 2009€ 2,114,203 for retigabine vs no add-on, per 1,000 patients. The probabilistic analyses showed that the likelihood that retigabine treatment is cost-effective is at least 70%. CONCLUSIONS: The estimated cost per additional QALY, for the retigabine vs no add-on treatment comparison, is well within the range of newly published estimates of willingness to pay for an additional QALY. Thus, add-on retigabine treatment for people with focal-onset epilepsy with no/limited response to standard antiepileptic treatment appears to be cost-effective.

Long term monitoring in refractory epilepsy: the Gowers Unit experience.

INTRODUCTION: Guidelines from the National Institute for Health and Clinical Excellence (NICE) and the International League Against Epilepsy recommend long term EEG monitoring (LTM) in patients for whom seizure or syndrome type is unclear, and in patients for whom it is proving difficult to differentiate between epilepsy and non-epileptic attack disorder (NEAD). The purpose of this study was to evaluate this recommended use of LTM in the setting of an epilepsy tertiary referral unit. METHODS: This study reviewed the case notes of all admissions to the Sir William Gowers Unit at the National Society for Epilepsy in the years 2004 and 2005. A record was made of the type, duration and result of all LTM performed both prior to and during the admission. Pre- and post-admission diagnoses were compared, and patients were divided according to whether LTM had resulted in a change in diagnosis, refinement in diagnosis or no change in diagnosis. The distinction between change and a refinement in the diagnosis was made on the basis of whether or not this alteration resulted in a change in management. RESULTS: 612 patients were admitted during 2004 and 2005, 230 of whom were referred for diagnostic clarification. Of these, LTM was primarily responsible for a change in diagnosis in 133 (58%) and a refinement of diagnosis in 29 (13%). In 65 (29%) patients the diagnosis remained the same after LTM. In those patients in whom there was a change in diagnosis, the most common change was in distinguishing epilepsy from NEAD in 73 (55%) and in distinguishing between focal and generalised epilepsy in 47 (35%). LTM was particularly helpful in differentiating frontal lobe seizures from generalised seizures and non-epileptic attacks. Inpatient ambulatory EEG proved as effective as video telemetry in helping to distinguish between NEAD, focal and generalised epilepsy. DISCUSSION: The study revealed that LTM led to an alteration in the diagnosis of 71% of patients referred to a tertiary centre for diagnostic clarification of possible epilepsy. Although LTM is relatively expensive, time consuming and of limited availability, this needs to be balanced against the considerable financial and social cost of misdiagnosed and uncontrolled seizures. This service evaluation supports the use of performing LTM (either video or ambulatory) in a specialist setting in patients who present diagnostic difficulty.

Case-control analysis of ambulance, emergency room, or inpatient hospital events for epilepsy and antiepileptic drug formulation changes.

PURPOSE: Although antiepileptic drugs (AEDs) with multisource generic alternatives are becoming more prevalent, no case-control studies have been published examining multisource medication use and epilepsy-related outcomes. This study evaluated the association between inpatient/emergency epilepsy care and the occurrence of a recent switch in AED formulation. METHODS: A case-control analysis was conducted utilizing the Ingenix LabRx Database. Eligible patients were 12-64 years of age, received >or=145 days of AEDs in the preindex period, had continuous eligibility for 6 months preindex, and no prior inpatient/emergency care. Cases received care between 7/1/2006 and 12/31/2006 in an ambulance, emergency room, or inpatient hospital with a primary epilepsy diagnosis. Controls had a primary epilepsy diagnosis in a physician's office during the same period. The index date was the earliest occurrence of care in each respective setting. Cases and controls were matched 1:3 by epilepsy diagnosis and age. Odds of a switch between "A-rated" AEDs within 6 months prior to index were calculated. RESULTS: Cases (n = 416) had 81% greater odds of having had an A-rated AED formulation switch [odds ratio (OR) = 1.81; 95% confidence interval (CI) = 1.25 to 2.63] relative to controls (n = 1248). There were no significant differences between groups regarding demographics or diagnosis. Significant differences were found with regard to medical coverage type (case Medicaid = 4.6%, control Medicaid = 1.8%, p = 0.002). Post hoc analysis results excluding Medicaid recipients remained significant and concordant with the original analysis. DISCUSSION: This analysis found an association between patients receiving epilepsy care in an emergency or inpatient setting and the recent occurrence of AED formulation switching involving A-rated generics.

Lacosamide: an adjunctive agent for partial-onset seizures and potential therapy for neuropathic pain.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of lacosamide, a new agent for use as adjunctive treatment in partial-onset seizures and a potential agent for treatment of neuropathic pain. DATA SOURCES: A MEDLINE search (1966-July 2009) was conducted using the key words lacosamide, harkoseride, SPM-927, ADD-234037, epilepsy, anticonvulsant, and neuropathic pain. Bibliographies of all articles retrieved were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All studies including humans and published in English with data describing lacosamide for the adjunctive treatment of partial-onset seizures and for treatment of neuropathic pain were reviewed. DATA SYNTHESIS: Lacosamide is a functionalized amino acid molecule that selectively enhances the slow inactivation of voltage-gated sodium channels and interacts with the collapsin-response mediator protein-2. With its bioavailability of approximately 100%, minimal protein binding, and few drug-drug interactions, lacosamide has a favorable pharmacokinetic profile. Recent data suggest that lacosamide may have a role as adjunctive treatment of partial-onset seizures. Open-label studies showed a 14-47% reduction in seizure frequency, while placebo-controlled trials demonstrated a 26-40% reduction in seizure frequency. The 50% responder rates ranged from 32.7% to 41.2% with varying doses of lacosamide. Although lacosamide use is not approved by the Food and Drug Administration for treatment of neuropathic pain, studies demonstrated reductions of 2.01-3.60 in pain scale scores. The most common adverse effects, occurring in greater than 10% of subjects in the clinical trials, include arthralgia, ataxia, blurred vision, diplopia, dizziness, fatigue, headache, injection site pain (only in intravenous studies), nausea, tremor, upper respiratory tract infection, and vomiting. CONCLUSIONS: Lacosamide is an effective agent for adjunctive treatment of refractory partial-onset seizures. Its exact role in the treatment of neuropathic pain needs to be determined.

[Pharmacoeconomic aspects of monotherapy of focal epilepsy]. / Farmakoékonomicheskie aspekty monoterapii fokal'noi épilepsii.

AIM: To perform a clinical/economic comparison of monotherapy with antiepileptic drugs (AED) in patients with newly diagnosed focal epilepsy (FE) based on the results of previous studies. MATERIAL AND METHODS: The most common AEDs (carbamazepine (CBZ), oxcarbazepine (OXZ), lamotrigine (LTG), lacosamide (LCM)) were compared in patients, aged 16 years and over, with illness duration of five years. RESULTS AND CONCLUSION: CBZ, OXZ and LCM can be used as monotherapy in patients with newly diagnosed FE. Monotherapy with LCM is associated with lowest costs for stopping focal seizures and the highest percentage of seizure-free patients. CBZ remains the most economical AED: the cost-effectiveness is minimal compared to all other AEDs used in the study. However, monotherapy with LCM is advisable if it is necessary to minimize side-effects in patients with newly diagnosed FE.

The cost-effective use of 18F-FDG PET in the presurgical evaluation of medically refractory focal epilepsy.

UNLABELLED: This study applied decision tree analysis to evaluate the sensitivity, specificity, and cost-effectiveness of clinical algorithms that incorporate 18F-FDG PET. METHODS: A cohort of 176 patients was studied. The localization rate, accuracy, therapeutic impact on the presurgical decision-making process, and correlation with the postsurgical outcome were assessed for the tests commonly performed for seizure localization. Decision tree sensitivity analysis compared 3 imaging strategies with a baseline strategy of medical therapy for all: video-electroencephalography monitoring (VEM)/MRI strategy, in which patients underwent VEM and brain MRI only, and +SPECT and +PET strategies, in which patients with an indeterminate VEM/MRI result underwent ictal SPECT or interictal 18F-FDG PET, respectively. RESULTS: The localization rates for VEM, MRI, 18F-FDG PET, ictal SPECT, and intracranial electroencephalography (EEG) were 62.2%, 35.8%, 75.0%, 60.0%, and 93.8%. The VEM/MRI strategy had the lowest cost per class I/II outcome, but the additional costs per class I/II outcome for the +PET and +SPECT strategies were always below the minimum reported cost savings for a class I/II outcome. There were no valid conditions in which the +SPECT strategy had a lower cost per class I/II outcome than the +PET strategy. Within the range of cost savings estimated to be associated with a class I/II outcome, all decision strategies produced net cost savings; however, these were significantly higher for the +PET and the +SPECT strategies. CONCLUSION: 18F-FDG PET is cost-effective in the presurgical evaluation, particularly when used in patients with a nonlocalizing or nonconcordant VEM or MRI result.

Impact of reimbursement restrictions on the choice of antiepileptic drugs: Belgian Study on Epilepsy Treatment (BESET).

BACKGROUND: In Belgium, new and costly antiepileptic drugs (AEDs) are only reimbursed as second-line treatment, after documented treatment with conventional and cheaper AEDs has failed. The objective of this study was to describe the treatment of epilepsy in Belgium and to analyze the impact of the reimbursement restrictions on the choice of AEDs. METHODS: Between May and June 2003, a sample of 100 neurologists, representative of the entire neurological community in teaching, academic, and regional hospitals in Belgium, were personally interviewed on the basis of a structured questionnaire (modified Rand method). The questionnaire contained questions on treatment choices and strategies in adult epilepsy. RESULTS: Unanimously, initial monotherapy was the preferred treatment strategy in all types of epilepsy. In the opinion of most neurologists, valproate was the first choice for idiopathic generalized and focal epilepsy with/without secondary generalization. Carbamazepine as their first choice for the treatment of focal epilepsy. New AEDs were most often prescribed as second-line therapy. Lamotrigine was the most frequently prescribed new AED and used for both generalized and focal epilepsy. It was followed by levetiracetam, topiramate and oxcarbazepine for focal epilepsy. In the absence of reimbursement restrictions, two new AEDs would be significantly more often prescribed as a first-line therapy: lamotrigine for idiopathic generalized epilepsy and oxcarbazepine for focal epilepsy. CONCLUSIONS: The neurologists reached a high level of consensus on many of the key treatment questions. Monotherapy with valproate and carbamazepine was the standard treatment strategy in Belgium. Lamotrigine and less so levetiracetam, topiramate and oxcarbazepine were commonly prescribed as second-line AEDs. In the absence of reimbursement restrictions, lamotrigine and oxcarbazepine would be more frequently prescribed.

[Medicoeconomic assessment of epilepsy surgery in adults with medically intractable partial epilepsy. Three-year outcomes from a multicenter French cohort]. / Evaluation médicoéconomique de la chirurgie des épilepsies partielles pharmacorésistantes de l'adulte. Résultats à trois ans d'une étude prospective multicentrique française.

PURPOSE: To compare resective surgery and medical therapy in a cost-effectiveness analysis in a multicenter cohort of adult patients with partial intractable epilepsy. POPULATION AND METHODS: Adult patients with partial, medically intractable, potentially operable epilepsy were eligible and followed every year over five years. Effectiveness was defined as one year without seizure. The long-term costs and effectiveness were extrapolated over the patients' lifetime with a Markov model. Productivity (indirect costs) and quality of life (QOLIE-31, SEALS) were also assessed. Changes before and after surgery were compared between the two groups. RESULTS: Two hundred and eighty-nine patients were included (119 with surgery, 161 medically treated, six not eligible, three lost to follow-up). One year after surgery, 81% of the patients were seizure-free; at two and three years, this rate was 78%. In the medical group, these rates were 10, 18, and 15%, respectively. The cost of the explorations was euro 8464; including surgery, it was euro 19,700. In the medical group, the average annual direct costs were between 3500 and euro 6000. At two years after surgery, the annual direct cost decreased to euro 2768, at three years, it was euro 1233, predominately antiepileptic drug costs. Surgery became cost-effective between seven and eight years. In the surgical group, all the quality-of-life scores improved at one year after surgery and were stable during the second and third years. CONCLUSION: Surgical therapy was cost-effective at the middle term even though indirect costs were not considered.

Budget Impact Analysis of Brivaracetam Adjunctive Therapy for Partial-Onset Epileptic Seizures in Valencia Community, Spain.

BACKGROUND AND OBJECTIVE: More than 30% of patients with epilepsy have inadequate control of seizures with drug therapy. The goal of this study is to determine the budget impact (BI) of the introduction of brivaracetam to the portfolio of approved drugs in Spain as adjunctive therapy for the treatment of partial-onset epilepsy in patients over 16 years old with a 5-year time horizon in the Valencia Community, a Spanish region with a population of 5 million. METHODS: The BI model compares the pharmaceutical expenditure on antiepileptics in two scenarios: with and without brivaracetam. It assumes that the introduction and increased use of brivaracetam will lead to a proportional decrease in consumption of coexisting adjunctive antiepileptics and calculates the evolution of the consumption of brivaracetam over 5 years (2016-2020). The model was designed from the perspective of the Spanish National Health System. Data on the candidate population, consumption of antiepileptics, market share and pharmaceutical expenditure were obtained from real-world data. Finally, a sensitivity analysis was carried out on the set of variables involved in the evolution of costs using a Monte-Carlo simulation. RESULTS: The model estimates that the target population eligible for adjunctive antiepileptics will hold at around 2352 between 2016 and 2020. Annual expenditure on antiepileptics is approximately €3.6 million. The number of patients eligible for treatment with brivaracetam would increase from 42 to 179 and annual savings of 0.09-0.37% would be created, representing €41,873 over 5 years (0.23% of the total budget). The sensitivity analysis corroborates that the probability of achieving savings with brivaracetam is around 84%. CONCLUSIONS: Brivaracetam is a therapeutic alternative that allows savings for the health system in patients with non-controlled epilepsy in monotherapy, having a fixed, predictable annual cost (independent of dose) from the first day of treatment as the lack of need for titration means the patient is within a range of therapeutic doses from the first dose.

The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.

[Analysis of the cost-effectiveness of treatment for refractory partial epilepsy: a simulation model for pregabalin and levetiracetam]. / Analisis coste-efectividad del tratamiento de la epilepsia parcial refractaria: un modelo de simulación de pregabalina y levetiracetam.

AIM: To estimate the cost-effectiveness (C-E) of pregabalin (PGB) or levetiracetam (LEV) relative to standard therapy (ST) as add-on anti-epileptic therapy in patients with partial refractory epilepsy in Spain. PATIENTS AND METHODS: Using stochastic simulation techniques, we estimated the C-E of PGB (300 mg/day) and LEV (2,000 mg/day) in a hypothetical cohort of 1,000 patients (vs ST). The model used data of efficacy and safety from two randomized controlled clinical trials. Direct medical costs (caused by handling of the disease and the adverse events were estimated using year-2007 prices. Model outcomes included number of additional seizure-free days (over one year), adverse events and quality adjusted life-years (QALYs). We calculated the incremental cost-effectiveness ratio (ICER) per additional seizure-free day and QALY gained. RESULTS: Compared with ST, treatment with PGB yielded an estimated 43.3 +/- 4.8 (mean +/- standard error) additional seizure-free days, and a gain of 0.04 +/- 0.0006 QALYs over one year. Comparable results for LEV vs ST were 24.3 +/- 6.2 and 0.025 +/- 0.007 QALYs, respectively. The annual total cost (in euros) per patient was 1,843 with PGB, 3,018 with LEV and 897 with ST. Mean ICER for PGB vs ST were 22 euros (95% CI = 19-27) per additional seizure-free day, and 23,881 euros (95% CI = 19,206-30,247) per QALY gained; estimates for LEV were 95 euros (CI 95% = 60-177) and 95,904 euros (CI 95% = 57,137-203,169) respectively. CONCLUSIONS: In patients with partial refractory epilepsy, when compared with ST, PGB demonstrated better ICER per additional seizure-free day and QALY gained than LEV.

Cost-Utility of Video-Electroencephalography Monitoring Followed by Surgery in Adults with Drug-Resistant Focal Epilepsy in Thailand.

OBJECTIVES: This study assessed whether video-electroencephalography (VEEG) monitoring followed by surgery was cost-effective in adult patients with drug-resistant focal epilepsy under Thai health care context, as compared with continued medical treatment without VEEG. METHODS: The total cost (in Thai Baht, THB) and effectiveness (in quality-adjusted life years, QALYs) were estimated over a lifetime horizon, using a decision tree and a Markov model. Data on short-term surgical outcomes, direct health care costs, and utilities were collected from Thai patients in a specialized hospital. Long-term outcomes and relative effectiveness of the surgery over medical treatment were derived, using systematic reviews of published literature. RESULTS: Seizure-free rates at years 1 and 2 after surgery were 79.4% and 77.8%, respectively. Costs of VEEG and surgery plus 1-year follow-up care were 216,782 THB, of which the VEEG and other necessary investigations were the main cost drivers (42.8%). On the basis of societal perspective, the total cost over a 40-year horizon accrued to 1,168,679 THB for the VEEG option, 64,939 THB higher than that for no VEEG. The VEEG option contributed to an additional 1.50 QALYs over no VEEG, resulting in an incremental cost-effectiveness ratio of 43,251 THB (USD 1236) per 1 QALY gained. Changes in key parameters had a minimal impact on the incremental cost-effectiveness ratio. Accounting for uncertainty, there was an 84% probability that the VEEG option was cost-effective on the basis of Thailand's cost-effective threshold of 160,000 THB/QALY. CONCLUSIONS: For patients with drug-resistant epilepsy, VEEG monitoring followed by epilepsy surgery was cost-effective in Thailand. Therefore it should be recommended for health insurance coverage.

Direct medical costs for partial refractory epilepsy in Mexico.

BACKGROUND: The aim was to determine the direct medical costs in patients with partial refractory epilepsy at the Mexican Institute of Social Security (IMSS) in Mexico. METHODS: We carried out a multicenter, retrospective-cohort partial-economic evaluation study of partial refractory epilepsy (PRE) diagnosed patients and analyzed patient files from four secondary- and tertiary-level hospitals. PRE patients >12 years of age with two or more antiepileptic drugs and follow-up for at least 1 year were included. The perspective was institutional (IMSS). Only direct healthcare costs were considered, and the timeline was 1 year. Cost techniques were microcosting, average per-service cost, and per-day cost, all costs expressed in U.S. dollars (USD, 2004). RESULTS: We reviewed 813 files of PRE patients: 133 had a correct diagnosis, and only 72 met study inclusion criteria. Fifty eight percent were females, 64% were <35 years of age, 47% were students, in 73% maximum academic level achieved was high school, and 53% were single. Fifty one percent of cases experienced simple partial seizures and 94% had more than one monthly seizure. Annual healthcare cost of the 72 patients was 190,486 USD, ambulatory healthcare contributing 76% and hospital healthcare with 24%. CONCLUSIONS: Annual mean healthcare cost per PRE patient was 2,646 USD; time of disease evolution and severity of the patient's illness did not affect costs significantly.

A cost comparison of alternative regimens for treatment-refractory partial seizure disorder: an econometric analysis.

BACKGROUND: Partial seizure disorder is typically treated by monotherapy with antiepileptic drugs (AEDs). However, when the condition is refractory to the initial treatment regimen, patients may be switched to monotherapy with another AED or to combination therapy with the initial AED plus a second AED. OBJECTIVES: The purpose of this study was to examine the economic costs associated with treatment-refractory partial seizure disorder and to compare the costs of 2 alternative approaches: a switch to oxcarbazepine (OXC) monotherapy or the addition to the regimen of another AED (AED add-on). METHODS: Adult patients with a diagnosis of partial seizure disorder who received initial AED monotherapy between January 1, 2000, and March 31, 2003, were identified from the PharMetrics Patient-Centric Database, a health plan administrative claims database. The medical and pharmacy history of these patients was analyzed from 6 months before a change to either OXC monotherapy or AED add-on therapy through 12 months after the change in treatment. Total health care resource utilization and the associated costs were compared within each cohort before and after the change, as well as between cohorts, with statistical differences tested using Wilcoxon rank sum tests. Multivariate econometric analyses were performed to examine the impact of age, sex, geographic location, Charlson Comorbidity Index, and the presence of specific comorbidities. RESULTS: Demographic and clinical characteristics 102 were similar between the OXC monotherapy cohort (n = 259) and the AED add-on cohort (n = 795). Annual direct treatment costs increased in both groups in the period after the failure of initial monotherapy, increasing from 10,462 US dollars to 11,360 US dollars in the OXC cohort and from 10,137 US dollars to 12,201 US dollars in the AED add on cohort (P < 0.01). Increased pharmacy costs were the primary driver behind cost increases in both cohorts. Patients in the AED add-on cohort were significantly more likely to have an emergency department visit during the period after the failure of initial monotherapy compared with the OXC monotherapy cohort (odds ratio = 1.52; P < 0.05). CONCLUSION: Despite limitations, the results of retrospective analysis of claims data suggest that the care of patients with treatment-refractory partial seizure disorder is costly and may vary significantly based on the pattern of care.

Outcomes associated with switching from monotherapy to adjunctive therapy for patients with partial onset seizures.

BACKGROUND: Some patients with partial onset seizures are drug-resistant and may benefit from adjunctive therapy. This study evaluated monotherapy/sequential monotherapy versus adjunctive therapy on use/costs. METHODS: Retrospective analysis using commercial/Medicare database (1 January 2007 to 31 December 2009). Patients with ≥2 diagnoses for partial onset seizures who received ≥2 prescriptions of the same antiepileptic drug were included. Outcomes assessed in the 12-month follow-up period were hospitalizations, ER visits, outpatient visits and prescription costs for patients who received monotherapy but switched to adjunctive. RESULTS: 1353 patients met criteria. After patients transitioned to adjunctive therapy, the average monthly percentage of patients with a hospitalization decreased from 5.3 to 3.0% (p < 0.0001). Similar results occurred with epilepsy-related hospitalizations (4.0 vs 1.7%, p < 0.0001). Adjusted costs decreased significantly (US$4205 vs 2944/month, p < 0.0001). Adjusted epilepsy-related costs decreased from US$1601 to 909/month (p < 0.0001). CONCLUSION: Adjunctive therapy in potentially drug-resistant patients with partial onset seizures can lead to reduced healthcare use and costs.

Analysis of direct hospital costs before and 18 months after treatment with vagus nerve stimulation therapy in 43 patients.

Vagus nerve stimulation (VNS) therapy is an established method for treating patients with refractory seizures. Although the initial cost of the device is about 10,000 US dollars, the battery life of the model 100 implanted in the patients in this analysis can exceed 5 years at standard settings. It is important to understand what type of cost-benefit can be expected after implantation. Our aim was to assess unplanned hospital costs 18 months before and 18 months after VNS implantation in 43 patients. The VNS therapy system was implanted according to standard procedures and stimulation of 0.75 to 2.0 mA was delivered either as 30 seconds on and 5 minutes off or 7 seconds on and 14 seconds off. Seizure frequency was calculated before and after 18 months of treatment. During this time no changes were made with other therapies for epilepsy. Hospitalization for emergency room (ER) visits, ward stays, and intensive care days were calculated according to the costs at Sahlgrenska University Hospital in Sweden. Therapy response was defined as 25% or greater reduction in seizure frequency. For all patients, intensive care unit (ICU) costs were reduced from 46,875 to 0 US dollars, ER visits from 13,000 to 9,000 US dollars, and ward stays from 151,125 to 21,375 US dollars. Total hospital costs for the 43 patients studied before VNS therapy were 211,000 US dollars and after 18 months of treatment were reduced to 30,375 US dollars, an average annual cost savings of approximately 3,000 US dollars per patient. The cost savings applied to all patients, irrespective of whether they responded to VNS therapy. VNS therapy resulted in annual reductions of approximately 3000 US dollars in unplanned hospital costs per study patient. Such direct savings sustained over the battery life of the VNS therapy system can equal or exceed the purchase price of the device.

Cost analysis of epilepsy surgery and of vigabatrin treatment in patients with refractory partial epilepsy.

In this study the direct actual costs associated with epilepsy-related health care, treatment with the novel antiepileptic drug vigabatrin (gamma-vinyl GABA, GVG), epilepsy surgery evaluation (ESE) and epilepsy surgery were analysed in 52 patients with intractable partial epilepsy who were on a waiting-list for ESE while trying GVG. Sixty percent of the 52 patients obtained a reduction in seizure frequency of 50% or more with GVG. Of the twenty-one operated patients 57% became seizure free, 10% had more than 75%, 5% had 50-75% and 29% had less than 50% reduction of seizure frequency. Of the 17 patients who did not go through ESE (the "GVG responders"), the corresponding outcome was 6%, 59%, 29% and 6%. For the 14 patients who were neither operated nor GVG responders, the outcome was 0%, 0%, 36% and 64%. The mean yearly costs (expressed in 1991 prices) of epilepsy-related health care including antiepileptic drug treatment was US $1,594 the year before starting GVG therapy, and US $2959 the first year of GVG treatment including a mean yearly cost of GVG of US $1,572. The mean total cost for ESE and surgery was US $46,778 (N = 21), while the mean cost of ESE in patients evaluated but not accepted for surgery (N = 14) was US $24,054. Considering the costs for ESE and surgery in the whole patient series, the mean total cost of rendering one patient seizure free with surgery was US $110,000. Surgery is the most effective treatment option in selected cases of severe partial epilepsy. If its costs are distributed over the patient's expected lifetime, the yearly cost is comparable to the present yearly cost of medication with GVG. However, since many patients achieve satisfactory seizure control with GVG, and considering the risks of surgery, we consider it a rational policy to let patients try this drug (or another of the new generation of antiepileptic drugs) before entering ESE.

Economic analysis of epilepsy treatment: a cost minimization analysis comparing carbamazepine and lamotrigine in the UK.

New anti-epileptic drugs differ from existing standard therapies not in their clinical efficacy, but in their side-effects profiles. To determine the relative economic value of these agents, one must compare drug costs, costs of resources employed in the management of adverse events, and costs associated with therapeutic switching. In this economic analysis, carbamazepine (CBZ) and lamotrigine (LTG) are evaluated in monotherapy treatment of partial and/or general tonic-clonic seizures in the UK. Adverse event and tolerability data are obtained from a published randomized controlled trial of CBZ vs. LTG. A Delphi panel of clinicians advised treatment patterns for adverse events. Cost data are obtained from public sources. Results show that CBZ therapy costs about one-third of LTG therapy (pound sterling 179 for CBZ vs. pound sterling 522 for LTG) even after the costs associated with the management of adverse events and therapeutic switching are considered.