Cost-effectiveness of cenobamate for focal seizures in people with drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to estimate the cost-effectiveness of add-on cenobamate in the UK when used to treat drug-resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively. METHODS: We estimated the cost per quality-adjusted life-year (QALY) for cenobamate compared to brivaracetam, eslicarbazepine, lacosamide, and perampanel in the UK National Health Service over a lifetime time horizon. We used a Markov cohort structure to determine response to treatment, using pooled data from three long-term studies of cenobamate. A network meta-analysis informed the likelihood of response to therapy with brivaracetam, eslicarbazepine, lacosamide, and perampanel relative to cenobamate. Once individuals discontinued treatment, they transitioned to subsequent treatment health states, including other antiseizure medicines, surgery, and vagus nerve stimulation. Costs included treatment, administration, routine monitoring, event management, and adverse events. Published evidence and expert opinion informed the likelihood of response to subsequent treatments, associated adverse events, and costs. Utility data were based on Short-Form six-dimension form utility. Discounting was applied at 3.5% per annum as per National Institute for Health and Care Excellence guidance. Uncertainty was explored through deterministic and probabilistic sensitivity analyses. RESULTS: In the base case, cenobamate led to cost savings of £51 967 (compared to brivaracetam), £21 080 (compared to eslicarbazepine), £33 619 (compared to lacosamide), and £28 296 (compared to perampanel) and increased QALYs of 1.047 (compared to brivaracetam), 0.598 (compared to eslicarbazepine), 0.776 (compared to lacosamide), and 0.703 (compared to perampanel) per individual over a lifetime time horizon. Cenobamate also dominated the four drugs across most sensitivity analyses. Differences were due to reduced seizure frequency with cenobamate relative to comparators. SIGNIFICANCE: Cenobamate improved QALYs and was less costly than brivaracetam, eslicarbazepine, lacosamide, and perampanel. Therefore, cenobamate may be considered as a cost-effective adjunctive antiseizure medication for people with drug-resistant focal seizures.

Budget impact analysis of betrixaban for venous thromboembolism prophylaxis in nonsurgical patients with acute medical illness in the United Kingdom.

OBJECTIVES: Venous thromboembolism (VTE) incurs substantial costs to the UK National Health Service (NHS). Betrixaban is approved in the US for VTE prophylaxis with a recommended 35-42 days of treatment. This analysis modeled the budget impact of introducing betrixaban for extended-duration VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the UK, where it is not yet licensed. METHODS: The 5-year budget impact of introducing betrixaban into current prophylaxis (low molecular weight heparin and fondaparinux) was estimated for the UK NHS. The Phase 3 APEX study provided primary event (VTE, myocardial infarction, ischemic stroke, and death; all-cause or VTE-related) and treatment complications data. Literature informed risk of recurrent events and long-term complications, population, market share, and costs for treatment and management of events. Network meta-analyses informed symptomatic DVT, pulmonary embolism and VTE-related death rates in fondaparinux patients. Deterministic sensitivity analyses explored uncertainty. RESULTS: Introducing betrixaban accrued savings of £1,290,000-£23,000,000 in years 1-5. Savings were from reduced primary VTE events, which reduced recurrent events and future complications. All sensitivity analyses showed savings. CONCLUSION: Introducing extended-duration VTE prophylaxis with betrixaban in the UK would accrue substantial savings annually over the next 5 years compared to current prophylaxis. Clinical trial registration: www.clinicaltrials.gov identifier is NCT01583218.

Effectiveness and safety of betrixaban extended prophylaxis for venous thromboembolism compared with standard-duration prophylaxis intervention in acute medically ill patients: a systematic literature review and network meta-analysis.

Aims: To determine the clinical effectiveness and safety of venous thromboembolism (VTE) prophylaxis using US- and Europe-approved anticoagulants relative to extended-duration VTE prophylaxis with betrixaban. Low molecular weight heparins (LMWHs), unfractionated heparin (UFH), fondaparinux sodium and placebo were each compared to betrixaban, as standard-duration VTE prophylaxis for hospitalized, non-surgical patients with acute medical illness at risk of VTE. Materials and methods: A systematic literature review was conducted up to June 2019 to identify randomized controlled trials (RCTs) of VTE prophylaxis in hospitalized, non-surgical patients with acute medical illness at risk of VTE. Studies that reported the occurrence of VTE events (including death) and, where possible, major bleeding, from treatment initiation to 20-50 days thereafter were retrieved and extracted. A Bayesian fixed effect network meta-analysis was used to estimate efficacy and safety of betrixaban compared with standard-duration VTE prophylaxis. Results: Seven RCTs were analyzed which compared betrixaban, LMWHs, UFH, fondaparinux sodium, or placebo. There were significantly higher odds (median odds [95% credible interval]) of VTE with LMWHs (1.38 [1.12-1.70]), UFH (1.60 [1.05-2.46]), and placebo (2.37 [1.55-3.66]) compared with betrixaban. There were significantly higher odds of VTE-related death with placebo (7.76 [2.14-34.40]) compared with betrixaban. No significant differences were observed for the odds of major bleeding with all comparators, VTE-related death with any active standard-duration VTE prophylaxis, or of VTE with fondaparinux sodium, compared with betrixaban. Limitations and conclusions: In this indirect comparison, betrixaban was shown to be an effective regimen with relative benefits compared with LMWHs and UFH. This indicates that betrixaban could reduce the burden of VTE in at-risk hospitalized patients with acute medical illness who need extended prophylaxis, though without direct comparative evidence, stronger conclusions cannot be drawn.

Cost-Effectiveness of Betrixaban Compared with Enoxaparin for Venous Thromboembolism Prophylaxis in Nonsurgical Patients with Acute Medical Illness in the United States.

BACKGROUND: Studies show that the risk of venous thromboembolism (VTE) continues post-discharge in nonsurgical patients with acute medical illness. Betrixaban is the first anticoagulant approved in the United States (US) for VTE prophylaxis extending beyond hospitalization. OBJECTIVE: The aim was to establish whether betrixaban for VTE prophylaxis in nonsurgical patients with acute medical illness at risk of VTE in the US is cost-effective compared with enoxaparin. METHODS: A cost-effectiveness analysis was conducted, estimating the cost per quality-adjusted life-year (QALY) gained with betrixaban (35-42 days) compared with enoxaparin (6-14 days) from a US payer perspective over a lifetime horizon. A decision tree (DT) estimated primary VTE events, thrombotic events, and treatment complications in the first 3 months based on data from the phase III Acute Medically Ill VTE Prevention with Extended Duration Betrixaban study. A Markov model estimated recurrent events and long-term complication risks from published literature. EuroQoL-5 Dimensions utility data and costs inflated to 2017 US dollars (US$) were from published literature. Results were discounted at 3.0% per annum. Deterministic and probabilistic sensitivity analyses explored uncertainty. RESULTS: Betrixaban dominated enoxaparin, with savings of US$784 and increased QALYs of 0.017 per patient. In addition, betrixaban dominated enoxaparin across all sensitivity analyses, but was most sensitive to utilities and DT probabilities. Furthermore, probabilistic sensitivity analysis found that betrixaban was more cost-effective than enoxaparin at all willingness-to-pay thresholds. CONCLUSION: Betrixaban can be considered cost-effective for nonsurgical patients with acute medical illness at risk of VTE, requiring longer VTE prophylaxis from hospitalization through post-discharge.