[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.

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.

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.

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.

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.

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.

Management of focal epilepsy in adults treated with polytherapy in France: the direct cost of drug resistance (ESPERA study).

PURPOSE: To estimate the direct costs associated with the current management of focal epilepsy in adults treated with a combination of antiepileptic drugs (AEDs) in France and the supplementary costs of drug resistant epilepsy as defined by the International League Against Epilepsy (ILAE) in 2009. METHODS: ESPERA was a multicentre, observational, cross-sectional study conducted in France in 2010. A random sample of neurologists, including specialists in epilepsy, prospectively enrolled adults with focal epilepsy treated with a combination of AEDs. Investigators classified their patients according to the 2009 ILAE criteria for drug resistance and this classification was then reviewed by two experts. All items of healthcare resource use associated with epilepsy over the previous year were documented retrospectively and valued from a societal perspective. RESULTS: Seventy-one neurologists enrolled 405 patients. After experts' review, 70.6% of patients were classified with drug-resistant epilepsy, 22.4% with drug-responsive epilepsy and 7% with undefined epilepsy. The mean annual epilepsy-related direct costs per patient were €4485±€4313 in patients with drug-resistant epilepsy compared to €1926±€1795 in patients with drug-responsive epilepsy. In these two groups, costs of AEDs were estimated at €2603 and €1544, respectively. Patients with drug-resistant epilepsy were more often hospitalised (mean annual cost: €1270 vs. €97) and underwent more additional tests (mean annual cost: €194 vs. €53). CONCLUSION: The direct cost of focal epilepsy in adults on AED combinations was estimated at €3850/patient/year. Drug resistance, as defined by the 2009 ILAE criteria, resulted in significant extra costs which varied with seizure frequency.

Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital.

BACKGROUND: Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy. METHODS: This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis. RESULTS: Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a treatment retention rate of 100%. The effectiveness of AED in terms of reduction of seizure frequency was highest for PHT (100%) and PHB (98%) followed by CBZ (96%) and VPA (95%). PHB and PHT were the cheapest of all AEDs (42 I$ and 56 I$/ year respectively). The costs of VPA and CBZ were two times and LTG and TOP were six to eight times higher. Adverse drug reaction (ADR) were observed among 140 (24.5%) of those with monotherapy. PHT (64%) was the most common drug to cause ADR, CBZ was at the bottom of the list to cause adverse effect (11.6%). VPA and PHB caused weight gain commonly. Adjustment of drug dose or withdrawal due to ADRs was necessary in 39% with PHT and 26% with PHB. CONCLUSION: Though PHT and PHB are cheapest and efficacious among all, CBZ and VPA are less costly, effective and well tolerated drug for seizure control in context of Bangladesh.

[A pharmacoeconomical analysis of idiopathic epilepsy].

We have analyzed pharmacoeconomical indicators in the treatment of idiopathic (generalized and focal) epilepsy in children and adolescence in an ambulatory treatment/diagnostic center of a big industrial city. In the total structure, focal epilepsy made up 41.73% (255 patients, 128 boys (50.2%) and 128 girls (49.8%)). Generalized forms were diagnosed in 61.96% (n=158) and partial forms - in 37.6% (n=97%) patients. Minimal direct and indirect costs for one patient were calculated for patients in remission and did not depend on the form of epilepsy. The costs increased by a magnitude of two or more for treatment efficiency 50% and by 3 times for insufficient efficiency of treatment of different forms of epilepsy. In case of a loss of control of seizures, indirect costs exceeded the economy of direct costs. Adequate treatment of idiopathic epilepsy in children is economically profitable because it allows to improve quality of life of a child and maintain manpower resources in the nearest future.

Impacto económico y en calidad de vida de la epilepsia resistente en España: estudio ESPERA / Quality of life and economic impact of refractory epilepsy in Spain: the ESPERA study

Introducción: El 30% de los pacientes con epilepsia no permanece libre de crisis con los fármacos antiepilépticos (FAE) disponibles actualmente. El objetivo del estudio fue estimar el impacto económico y en calidad de vida de la epilepsia resistente a fármacos (ERF) en España, según la definición de la Liga Internacional contra la Epilepsia (ILAE). Métodos: Estudio observacional retrospectivo (12 meses) que incluyó pacientes adultos con epilepsia focal en tratamiento con, al menos, 2 FAE. Los costes sanitarios directos (€ 2010) se cuantificaron a partir de los recursos sanitarios y de sus costes unitarios. El análisis se realizó desde las perspectivas del Sistema Nacional de Salud (SNS) y la sociedad. El impacto de la ERF en la calidad de vida se valoró mediante los cuestionarios QOLIE 31-P, EQ-5D-3L y NDDIE. Resultados: Se analizaron 263 pacientes (304 seleccionados). El 70,0% tenía ERF y el 20,3% estaban controlados. Bajo la perspectiva del SNS el coste anual por paciente con ERF y por paciente controlado fue de 4.964 y 2.978 €, respectivamente (p<0,01). En relación con los pacientes con ERF, los pacientes controlados presentaron mejores puntuaciones en el QOLIE-31P (70,8 vs 56,4, p<0,0001) y EQ-5D-3L (75,6 vs 64,7, p<0,001), y menor incidencia de depresión mayor según la escala NDDIE (23 vs 8,3%, p<0,05). Conclusiones: En relación con la epilepsia controlada, la ERF se asocia a mayor consumo de recursos y costes, peor calidad de vida y mayor incidencia de depresión mayor, resultando, por tanto, en una considerable carga para el SNS y la sociedad (AU)

Introduction: Despite use of currently available anti-epileptic drugs (AED), 30% of epilepsy patients are not seizure-free. The purpose of this study was to estimate the quality of life and economic impact in Spain of drug-resistant epilepsy (DRE), as defined by the International League Against Epilepsy (ILAE). Methods: Observational retrospective 12-month study conducted in Spain including adults with focal epilepsy treated with at least two AEDs. Direct costs (€ 2010) were calculated based on health care resources used and their official unit costs. Costs were analysed from the perspectives of the Spanish National Health System (SNS) and society. The impact of DRE on patients’ quality of life was examined using the QOLIE 31-P, EQ-5D-3L, and NDDIE questionnaires. Results: We analysed 263 patients out of the 304 recruited. According to ILAE criteria, 70.0% of the patients had drug-resistant epilepsy, while 20.3% achieved seizure freedom. From the viewpoint of the SNS, annual costs for resistant and seizure-free patients were € 4964 and € 2978 respectively (P<.01). Compared to resistant patients, seizure-free patients showed better scores on QOLIE-31P (70.8 vs 56.4, P<.0001) and EQ-5D-3L (75.6 vs 64.7, P<.001). Seizure-free patients showed a lower incidence of major depression compared to resistant patients according to the NDDIE scale (23 vs 8.3%, P<.05). Conclusions: Results suggest that DRE is associated with increased use of healthcare resources and consequently with higher costs, poorer quality of life and higher incidence of major depression compared to seizure-free patients, thus representing a considerable burden to the SNS and society (AU)

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.

Retigabine for the adjunctive treatment of adults with partial-onset seizures in epilepsy with and without secondary generalization : a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of retigabine (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of adults with partial-onset seizures in epilepsy, with and without secondary generalization, as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination was commissioned to act as the Evidence Review Group (ERG). The ERG undertakes a critical review of the clinical and cost-effectiveness evidence of the technology based upon the manufacturer's submission to NICE. The ERG also independently searches for relevant evidence and evaluates modifications to the manufacturer's decision-analytic model. This paper provides a description of the company submission, the ERG review and NICE's subsequent decisions. The clinical effectiveness data were derived from three placebo-controlled randomized controlled trials (RCTs). A meta-analysis pooling across all doses of retigabine found beneficial effects of retigabine in terms of responder rate (odds ratio [OR] 2.79; 95 % CI 2.08, 3.76) and rate of seizure freedom (OR 2.54; 95 % CI 0.92, 6.98) [both double-blind phase analyses]. When compared in a network meta-analysis with the selected comparator antiepileptic drugs (AEDs) [eslicarbazepine acetate, lacosamide, pregabalin, tiagabine and zonisamide], retigabine offered broadly similar efficacy in terms of responder rate and freedom from seizure. The de novo decision-analytic model presented within the submission evaluated the cost effectiveness of retigabine compared with these AEDs and no treatment (i.e. maintenance therapy). After numerous additional analyses, the ERG considered the use of retigabine to be not cost effective for NICE at thresholds below £43,000 if no treatment was considered a relevant comparator. The NICE Appraisal Committee decided that an appropriate comparator was an active treatment. The Committee recommended that retigabine is offered as an option for the adjunctive treatment of partial-onset seizures with or without secondary generalization in adults aged 18 years and older with epilepsy, only when previous treatment with carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate and topiramate has not provided an adequate response, or has not been tolerated.

Antiepileptic drug treatment patterns and economic burden of commercially-insured patients with refractory epilepsy with partial onset seizures in the United States.

OBJECTIVE: To assess the economic burden in direct healthcare utilization and costs for refractory epileptic patients with partial onset seizures (POS) and assess the antiepileptic drug (AED) treatment patterns among these patients. METHODS: This retrospective database study analyzed administrative claims of commercially-insured patients with POS from 2004-2008. Healthcare costs and utilization were compared between refractory (defined as ≥3 AEDs) and non-refractory patients by calendar year and AED treatment patterns were described for refractory patients. RESULTS: Of the 79,149 patients identified (mean age 33 years; 54.8% female), 8714 (11%) were classified as refractory. In 2008, average annual healthcare costs for refractory patients were significantly higher than non-refractory patients ($33,613 vs $19,085), also by settings for inpatient ($11,780 vs $6076), outpatient ($13,431 vs $8637), and pharmacy costs ($8402 vs $4372) (all p < 0.001). Among refractory patients, close to one-third of total costs were for POS-related services. Similar trends were observed when assessing POS-related utilization and costs. The differences were consistent across all calendar years examined. Among refractory patients, 80.5% were on monotherapy at the beginning of the follow-up period. Levetiracetam is the common AED in mono/combination therapy as well as add-on/switch-to. LIMITATIONS: The onset of seizure cannot be identified, and the indication of each AED could not be confirmed from the pharmacy claims. Only direct medical costs were assessed. CONCLUSIONS: Pattern of use was very dynamic, suggesting seizures are not well-controlled. Improving seizure control and reducing economic burden of refractory epilepsy remain important unmet medical needs in this population.

The cost effectiveness of newer epilepsy treatments: a review of the literature on partial-onset seizures.

BACKGROUND AND OBJECTIVE: Epilepsy is one of the most common neurological disorders, affecting more than 3 million people in Europe. This paper reviews the published evidence regarding the cost effectiveness of second-generation antiepileptic drugs (AEDs). METHODS: A systematic literature search was performed, using the databases Academic Search Complete, Econlit, EMBASE and MEDLINE. Health economic evaluations of newer (second-generation) AEDs, published as full-length journal articles, were searched for. We focused on evaluations of newer AEDs as treatment for partial-onset seizures. 470 studies were initially identified and 19 were finally included. Information regarding (i) AEDs studied, (ii) cost effectiveness, and (iii) a variety of health economic modelling specifics was extracted from each study. Then, the included studies were summarized and a quality assessment was performed, according to the British Medical Journal's guidelines for economic studies. RESULTS: The results were as follows: (i) the cost per additional QALY for newer AEDs used as adjunctive treatment, compared with standard therapy, ranged between $US19 139 (levetiracetam) and $US57 210 (pregabalin) [year 2010 values]; no cost-effectiveness evidence was identified for felbamate, eslicarbazepine, oxcarbazepine or tiagabine; and (ii) all studies met at least 60% of the British Medical Journal's guidelines criteria, and seven studies were found to satisfy more than 80% of the criteria. Guidelines criteria not met involve inadequate reporting of input data and modelling details, including validation and availability of models used for cost-effectiveness calculations. CONCLUSIONS: Although failure to meet good practice guidelines influences the reliability of the presented evidence adversely, a sufficient number of the included studies were found to comply enough with the guidelines in order for the qualitative content of the cost-effectiveness results - that some of the newer AEDs are cost effective - to be reliable. In fact, this conclusion is likely to be relatively robust, since the effect of improved seizure control on labour market performance was not included in the base-case results in any of the included studies and improved seizure control need only to have a moderate effect on sickness absenteeism in order for the corresponding treatment to be cost effective even when willingness to pay for an additional QALY is low. However, the cost effectiveness of newer AEDs has only been studied for a small number of settings, and hence future studies incorporating additional settings are needed.

Costs, work absence, and adherence in patients with partial onset seizures prescribed gabapentin or pregabalin.

BACKGROUND/OBJECTIVE: Few studies have examined cost of illness of epileptic partial onset seizures (POS) from the employer perspective or compared users of gabapentin and pregabalin in treatment of POS. This study compares pharmacotherapy, direct/indirect costs, and work absences of patients with POS newly started on gabapentin or pregabalin. METHODS: Data from employees and dependent spouses with POS starting treatment (index date) with either gabapentin or pregabalin were analyzed. Patients were required to have at least 6 months of health plan enrollment pre- and post-index. Regression modeling compared medical and prescription costs, sick leave (SL), short-term disability (STD), workers' compensation (WC) costs and absence days during the 6-month post-index period. Persistence, adherence (proportion of days covered), impact on adherence of copay, and copay as a percent of salary were modeled. RESULTS: Semiannual medical, drug, SL, STD, and WC costs for gabapentin vs. pregabalin cohorts were $10,306 vs. $9186, $2353 vs. $3387 (P=0.01), $552 vs. $342, $1280 vs. $580, and $170 vs. $30, respectively. SL days (10.8 vs. 1.5, P=0.04) and STD days (9.8 vs. 6.2) were lower in the pregabalin cohort. Persistence (median 94 vs. 70 days) and proportion with ≥ 80% adherence (30% vs. 15%, P=0.049) were greater in the pregabalin cohort. Adherence decreased as copay or copay as a percent of salary increased beyond specific levels in both cohorts. CONCLUSION: Despite higher acquisition costs for branded pregabalin over generic gabapentin, overall direct and indirect costs trended lower for pregabalin users. Additionally, pregabalin users had significantly fewer sick leave days and significantly higher adherence rates than gabapentin users.

An audit of the presurgical evaluation and patient selection for extratemporal resective epilepsy surgery in a resource-poor country.

PURPOSE: The selection of ideal candidates for extratemporal resective epilepsy surgery is a challenge in resource-poor countries because of the limited presurgical diagnostic facilities and their affordability. To audit the presurgical evaluation strategy and selection for extratemporal resective epilepsy surgery in a resource-poor region. METHODS: From the prospective database maintained at an epilepsy surgery center in southern India, we reviewed the data of consecutive patients who underwent presurgical evaluation from January 2005 through December 2008 for antiepileptic drug-resistant focal epilepsies emanating from the frontal, parietal and occipital lobes. Out of 285 patients, only 71 (24.9%) underwent resective surgery; the remaining 214 (75.1%) patients could not be selected for surgery. We inquired the reasons for their exclusion from surgery. RESULTS: The difference in the rates of seizure-free outcome between surgical and non-surgical groups was highly significant (73.2% vs. 7.7%, P<0.0005). The major reasons for exclusion from surgery were normal MRI in 107 (50%), inability to afford invasive EEG monitoring in 40 (18.7%) and lesion location adjacent to eloquent cortical areas in 27 (12.6%) patients. While clustering of seizures and presence of preoperative neurological deficits favored surgical selection, the presence of secondary generalized seizures and discordant interictal epileptiform abnormalities were associated with exclusion from surgery. CONCLUSIONS: We conclude that, in a resource-poor country, ideal candidates for extratemporal resective epilepsy surgery are those with well-circumscribed lesions not adjoining eloquent cortical areas. In such patients, concordant EEG findings and absence of preoperative secondary generalized seizures reinforce selection for surgery.

Cost effectiveness of lacosamide in the adjunctive treatment of patients with refractory focal epilepsy in Belgium.

OBJECTIVES: Lacosamide is an anti-epileptic drug, indicated as adjunctive therapy for patients with focal seizures with or without secondary generalization. This study aims to assess the cost effectiveness of standard anti-epileptic drug therapy plus lacosamide 300 mg/day compared with standard therapy alone from the perspective of the Belgian healthcare payer. METHODS: The treatment pathway of a hypothetical cohort of 1000 patients over 2 years was simulated using a decision tree. Data about health state probabilities, seizure frequency and utility values were taken from lacosamide trials or from the literature. Effectiveness measures included the number of seizures avoided and the number of quality-adjusted life-years gained. Unit costs were taken from national references. Resource use was estimated by a panel of eight neurologists with extensive experience in epilepsy. The price year was 2008. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Over a 24-month period, standard anti-epileptic drug therapy plus lacosamide led to a reduction of seven seizures, an increase of 0.038 quality-adjusted life-years and a cost decrease of &U20AC;3619 per patient compared with standard therapy alone. Using a willingness to pay of &U20AC;30 000 per quality-adjusted life-year, the net monetary benefit of standard anti-epileptic drug therapy plus lacosamide amounted to &U20AC;4754. The probability of standard anti-epileptic drug therapy plus lacosamide being cost effective was 97.3%, 99.8%, 99.9% and 100% at 6, 12 , 18 and 24 months, respectively. CONCLUSION: In patients with difficult-to-treat epilepsy, standard anti-epileptic drug therapy plus lacosamide appears to be a cost-effective option in Belgium.

Lacosamide as adjunctive therapy for partial-onset epileptic seizures: a review of the clinical and economic literature.

OBJECTIVE: This article provides a short but comprehensive pharmacotherapeutic update of adjunctive therapy with lacosamide for partial-onset seizures in adult patients. RESEARCH DESIGN AND METHODS: PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, EconLit were searched from January 1999 to September 2010. Studies evaluating intravenous lacosamide were excluded because this article focuses on chronic adjunctive therapy. RESULTS: Three randomised, multicentre, double-blind, placebo-controlled trials have investigated the efficacy of lacosamide in 1300 adults with epilepsy. The median percent reduction in seizure frequency per 28 days from baseline to maintenance was 18.4% for placebo, 33.3% for lacosamide 200 mg/day (p < 0.01), 36.8% for 400 mg/day (p < 0.001), 39.4% for 600 mg/day. The percentage of patients attaining a seizure frequency reduction of ≥50% was 22.6% with placebo, 34.1% with lacosamide 200 mg/day (p < 0.05), 39.7% with lacosamide 400 mg/day (p < 0.001), 39.6% with lacosamide 600 mg/day. Three open-label extension studies showed that long-term treatment with lacosamide produced sustained efficacy in and was well-tolerated by patients. Three economic evaluations used a similar design to determine the cost effectiveness of lacosamide from the healthcare payer perspective in Sweden, Finland and Belgium. These studies showed that standard anti-epileptic drug therapy plus lacosamide is likely to constitute a cost-effective alternative. The budget impact of introducing lacosamide is likely to be limited. CONCLUSIONS: The evidence on lacosamide was limited and studies suffered from a number of methodological limitations. Lacosamide appears to be a safe, efficacious and cost-effective adjunctive therapy for partial-onset epileptic seizures in adult patients. However, these results need to be validated by studies that explore the impact of lacosamide in real-life clinical practice.

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.

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.