Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain.

OBJECTIVE: This study aims to assess the cost utility of Brivaracetam compared with the third-generation anti-epileptic drugs used as standard care. METHODS: A cost utility analysis of Brivaracetam was carried out with other third-generation comparators. The treatment pathway of a hypothetical cohort over a period of 2 years was simulated using the Markov model. Data for effectiveness and the QALYs of each health status for epilepsy, as well as for the disutilities of adverse events of treatments, were analyzed through a studies review. The cost of the anti-epileptics and the use of medical resources linked to the different health statuses were taken into consideration. A probabilistic sensitivity analysis was performed using a Monte Carlo simulation. RESULTS: Brivaracetam was shown to be the dominant alternative, with Incremental Cost Utility Ratio (ICUR) values from -11,318 for Lacosamide to -128,482 for Zonisamide. The probabilistic sensitivity analysis validates these results. The ICUR sensitivity is greater for increases in the price of Brivaracetam than for decreases, and for Eslicarbizapine over the other adjunctives considered in the analysis. CONCLUSIONS: Treatment with Brivaracetam resulted in cost effective and incremental quality adjusted life years come at an acceptable cost.

Comparative economic outcomes in patients with focal seizures initiating eslicarbazepine acetate versus brivaracetam as their first adjunctive ASD.

AIMS: To study the association between initiation of first adjunctive therapy with eslicarbazepine acetate (ESL) vs. brivaracetam (BRV) on healthcare resource utilization (HCRU) and charges among patients with treated focal seizures (FS). MATERIALS AND METHODS: Symphony Health's Integrated Dataverse (IDV) claims data (1 April 2015 to 30 June 2018) were used to identify two cohorts as first adjunctive therapy with ESL or BRV following a generic anti-seizure drug (ASD). The index date was the earliest claim for a new ESL or BRV prescription. Key inclusion criteria were only 1 generic ASD in the 12 months before the index date; ≥1 medical claim with an FS diagnosis. Unit of analysis was the 90-day person-time-block. Changes in HCRU and charges were assessed using a difference-in-differences framework. Both unadjusted and adjusted analyses were performed. The adjusted model utilized person-specific fixed effects and propensity score-based weighting to control for differences in baseline covariates. Bias-corrected bootstrap confidence intervals (CIs) were calculated for charge outcomes. RESULTS: 208 and 137 patients initiated first adjunctive therapy with ESL (43.7 years, 51.9% female) or BRV (39.3 years, 51.8% female). Patients in the ESL cohort had numerically larger reductions in all-cause and FS-related inpatient hospitalizations and outpatient visits and FS-related emergency department visits. Compared to patients initiating BRV, patients treated with ESL had significantly larger reductions in total charges (-$3,446, CI: -$13,716, -$425), all-cause (-$3,166, CI: -$13,991, -$323) and FS-related (-$2,969, CI: -$21,547, -$842) medical charges, all-cause (-$3,397, CI: -$15,676, -$818) and FS-related (-$2,863, CI: -$19,707, -$787) outpatient charges, and non-ASD-related prescription charges (-$420, CI: -$1,058, -$78). LIMITATIONS: Claims may be missing, or miscoded; outcomes may be influenced by variables not accounted for in the analysis; only information on submitted charges was included. CONCLUSIONS: Among patients with FS, initiation of first adjunctive therapy with ESL was associated with significantly larger reductions in medical and non-ASD-related prescriptions charges compared to BRV.

Economic Value of Adjunctive Brivaracetam Treatment Strategy for Focal Onset Seizures in Finland.

INTRODUCTION: There is an unmet need for well-tolerated antiepileptic drugs (AEDs) that effectively control focal onset seizures. This study aimed to evaluate the economic value of new AEDs in the treatment of focal onset seizure, with or without secondary generalization, in Finnish adults and adolescents with epilepsy, comparing brivaracetam with perampanel as adjunctive AEDs. METHODS: Economic value was assessed using cost-utility analysis. Periods of AED initiation, titration, response assessment (seizure freedom, ≥ 50% reduction, no response), switching in no response or treatment-emergent adverse events (TEAEs), and death were simulated using a discrete-event simulation model. Responses and switching were simulated based on a comprehensive Bayesian network meta-analysis. The primary modeled outcome was the 3%/year discounted incremental cost-effectiveness ratio (ICER). Discounted quality-adjusted life-years (QALYs), payer costs (year 2017 Euro) per patient, and net monetary benefit (NMB) were secondary outcomes. Probabilistic and comprehensive deterministic sensitivity analyses were conducted. RESULTS: Brivaracetam was more efficacious and had fewer TEAEs than perampanel and other AEDs. Modeled average 5-year QALYs and costs were 3.671 and €28,297 for brivaracetam and 3.611 and €27,979 for perampanel, respectively. The resulting ICER for brivaracetam versus perampanel was only €5345/QALY gained in a deterministic base case scenario. Brivaracetam had a positive NMB and high probability of cost-effectiveness of €1190 and 71% or €1944 and 80% with the assumed willingness to pay of €25,358 or €38,036/QALY gained, respectively. The primary result was robust, with a positive NMB persistent in all sensitivity analysis scenarios. When switching from brivaracetam to perampanel was excluded from the modeling or switching from perampanel to brivaracetam was included, brivaracetam was cost-saving and more effective than perampanel (dominant). CONCLUSION: These simulated comparisons demonstrated that brivaracetam was more effective and potentially also more affordable than perampanel. Thus, brivaracetam is likely a cost-effective and net beneficial alternative to perampanel for treatment of focal onset seizures. Plain language summary available for this article.

Cost-effectiveness of raltegravir in antiretroviral treatment-experienced HIV-1-infected patients in Switzerland.

OBJECTIVES: Raltegravir, a novel integrase inhibitor, has shown great efficacy in reducing HIV viral load among treatment-experienced patients. A cohort state-transition model was used to assess the long-term effect of raltegravir treatment on costs and quality-adjusted life expectancy from a Swiss perspective. METHODS: Patients were stratified into health states according to opportunistic infection status, HIV RNA level, and CD4 count, with each group assigned a treatment cost and utility (quality of life) score. Model inputs came from published studies, clinical trials, and database analyses. Results were used to calculate incremental cost-effectiveness ratio (ICER) of raltegravir use, expressed in Swiss francs (CHF) as incremental cost/quality-adjusted life-year (QALY) gained. Future costs and QALYs were discounted at 3% per year. RESULTS: Five years of raltegravir treatment increased discounted quality-adjusted life expectancy by 3.73 years over placebo, with additional discounted cost of CHF 170,347, resulting in an ICER of CHF 45,687/QALY. ICERs ranged from CHF 42,751 to 53,478/QALY for treatment duration of 3 and 10 years, respectively. Results were most sensitive to changes in raltegravir treatment duration, source of estimated quality of life weights, and raltegravir price. CONCLUSIONS: Adding raltegravir to optimized background therapy was a cost-effective strategy for treatment-experienced patients in Switzerland.

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.

Clinical impact and cost-effectiveness of making third-line antiretroviral therapy available in sub-Saharan Africa: a model-based analysis in Côte d'Ivoire.

OBJECTIVE: In sub-Saharan Africa, HIV-infected adults who fail second-line antiretroviral therapy (ART) often do not have access to third-line ART. We examined the clinical impact and cost-effectiveness of making third-line ART available in Côte d'Ivoire. METHODS: We used a simulation model to compare 4 strategies after second-line ART failure: continue second-line ART (C-ART2), continue second-line ART with an adherence reinforcement intervention (AR-ART2), immediate switch to third-line ART (IS-ART3), and continue second-line ART with adherence reinforcement, switching patients with persistent failure to third-line ART (AR-ART3). Third-line ART consisted of a boosted-darunavir plus raltegravir-based regimen. Primary outcomes were 10-year survival and lifetime incremental cost-effectiveness ratios (ICERs), in $/year of life saved (YLS). ICERs below $3585 (3 times the country per capita gross domestic product) were considered cost-effective. RESULTS: Ten-year survival was 6.0% with C-ART2, 17.0% with AR-ART2, 35.4% with IS-ART3, and 37.2% with AR-ART3. AR-ART2 was cost-effective ($1100/YLS). AR-ART3 had an ICER of $3600/YLS and became cost-effective if the cost of third-line ART decreased by <1%. IS-ART3 was less effective and more costly than AR-ART3. Results were robust to wide variations in the efficacy of third-line ART and of the adherence reinforcement, as well as in the cost of second-line ART. CONCLUSIONS: Access to third-line ART combined with an intense adherence reinforcement phase, used as a tool to distinguish between patients who can still benefit from their current second-line regimen and those who truly need third-line ART would provide substantial survival benefits. With minor decreases in drug costs, this strategy would be cost-effective.

The potential cost and benefits of raltegravir in simplified second-line therapy among HIV infected patients in Nigeria and South Africa.

BACKGROUND: There is an urgent need to improve the evidence base for provision of second-line antiretroviral therapy (ART) following first-line virological failure. This is particularly the case in Sub-Saharan Africa where 70% of all people living with HIV/AIDS (PHA) reside. The aim of this study was to simulate the potential risks and benefits of treatment simplification in second-line therapy compared to the current standard of care (SOC) in a lower-middle income and an upper-middle income country in Sub-Saharan Africa. METHODS: We developed a microsimulation model to compare outcomes associated with reducing treatment discontinuations between current SOC for second-line therapy in South Africa and Nigeria and an alternative regimen: ritonavir-boosted lopinavir (LPV/r) combined with raltegravir (RAL). We used published studies and collaborating sites to estimate efficacy, adverse effect and cost. Model outcomes were reported as incremental cost effectiveness ratios (ICERs) in 2011 USD per quality adjusted life year ($/QALY) gained. RESULTS: Reducing treatment discontinuations with LPV/r+RAL resulted in an additional 0.4 discounted QALYs and increased the undiscounted life expectancy by 0.8 years per person compared to the current SOC. The average incremental cost was $6,525 per treated patient in Nigeria and $4,409 per treated patient in South Africa. The cost-effectiveness ratios were $16,302/QALY gained and $11,085/QALY gained for Nigeria and South Africa, respectively. Our results were sensitive to the probability of ART discontinuation and the unit cost for RAL. CONCLUSIONS: The combination of raltegravir and ritonavir-boosted lopinavir was projected to be cost-effective in South Africa. However, at its current price, it is unlikely to be cost-effective in Nigeria.

Cost-effectiveness of raltegravir in HIV/AIDS.

Raltegravir is a first-in-class HIV-1 integrase inhibitor with established antiviral efficacy in treatment-naive and treatment-experienced patients with multidrug-resistant HIV-1 infection. In this article, we summarize pharmacoeconomic evaluations of raltegravir-based treatment regimens, compared with alternative therapies, in the treatment of patients with HIV infection and/or AIDS. Cost-effectiveness evaluations of raltegravir in treatment-experienced patients conducted using a continuous-time, state-transition Markov cohort model suggest that raltegravir, combined with optimized background therapy, falls within the range that would generally be considered cost effective compared with optimized therapy alone in Spanish, Swiss and UK health systems. In treatment-naive populations, raltegravir was evaluated using a three-stage continuous-time state-transition cohort model. Raltegravir-based initiation treatment strategies (first-line raltegravir) were compared with protease inhibitor and non-nucleoside reverse-transcriptase inhibitor initiation strategies, in which raltegravir was retained for salvage therapy. First-line raltegravir was cost-effective versus retaining raltegravir for salvage therapy in several European populations. A separate economic model was used to evaluate first-line raltegravir against two alternative initiation regimens representing standard clinical practice in Australia; raltegravir proved to be cost effective in both scenarios. In all studies examined, results were sensitive to factors including treatment duration, mortality rate, analytic time horizon, health utility weights, cost of raltegravir and optimized therapy, incidence of opportunistic infection and discount rates. Nonetheless, raltegravir remained cost effective under most scenarios.

Cost-effectiveness analysis of raltegravir in treatment-experienced HIV type 1-infected patients in Spain.

Raltegravir, a novel HIV-1 integrase inhibitor, has superior efficacy with optimized background treatment (OBT) vs. placebo + OBT in treatment-experienced HIV-1 patients. This study assessed the long-term cost effectiveness of raltegravir from a Spanish National Healthcare System perspective. A cohort-state-transition model was used to estimate clinical and economic outcomes associated with raltegravir + OBT vs. OBT alone. Subjects were stratified into health states according to HIV RNA level, CD4 count, and opportunistic infection (OI) history, and could transition into different health states over time based on projected long-term efficacy. Each health state was associated with a distinct treatment cost and utility (QoL) score. Model inputs for mortality, resource utilization, unit costs, OI risk, and long-term durability of viral suppression were obtained from clinical trials, published studies, and database analyses. Model outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2007 Euros per quality-adjusted life-year (euro/QALY) gained. Costs and QALYs were discounted at 6% per year based on Spanish cost-effectiveness guidelines. Extensive sensitivity analyses were conducted. Five years of treatment with raltegravir + OBT resulted in an additional 4.5 years of undiscounted life expectancy vs. OBT alone. The ICER of raltegravir + OBT vs. OBT alone was euro22,908/QALY and euro31,431/QALY for 3- and 5-year use, respectively. Lower ICERs were observed with lower discount rates (3%) for costs and benefits, lower raltegravir price (20%), and shorter treatment duration (3 years). ICER was also sensitive to analytical time horizon and alternative sources of QoL scores. In treatment-experienced Spanish patients, raltegravir was projected to provide survival benefits and be cost effective.