Cost-effectiveness of rivaroxaban versus apixaban for the initial treatment of venous thromboembolism and extended prevention of recurrences in the UK

Abstract

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban vs apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose, as the 20-mg dose has already been evaluated.

Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15?mg twice daily for 3 weeks, followed by 20?mg once daily for 6 months, then extended prevention with 10?mg once daily) or apixaban (10?mg twice daily for 1 week, followed by 5?mg twice daily for 6 months, then extended prevention with 2.5?mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0–6?months) and an extended prevention phase (6–18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature.

Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban.

Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data.

Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.     

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada.

Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($).

Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies.

Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.     

Cost analysis of plasma-derived factor VIII/von Willebrand factor versus recombinant factor VIII for treatment of previously untreated patients with severe hemophilia A in the United States

Background: Inhibitor development to factor VIII (FVIII) hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study, the first randomized controlled trial to compare the immunogenicity of plasma-derived FVIII (pdFVIII)/von Willebrand factor (VWF) and recombinant-DNA-derived FVIII (rFVIII), demonstrated higher inhibitor rates in previously untreated patients (PUPs) treated with rFVIII than in PUPs treated with pdFVIII/VWF.

Objective: To quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII.

Methods: An Excel-based clinical and economic model was developed from a US healthcare payer perspective and run over a 5-year period. The analysis utilized a cohort approach to model patient treatment and outcomes over a monthly cycle to quantify differences in costs of FVIII, bypassing agents, and hospitalizations for serious bleeds. Rates of high-titer inhibitor development were obtained from the SIPPET study. Patients developing high-titer inhibitors were treated with immune tolerance induction (ITI). Patients who developed low-titer inhibitors and those who did not develop inhibitors continued their usual FVIII treatment. Patients who were successfully treated with ITI returned to FVIII treatment, while unsuccessfully treated patients received bypassing agents. Total costs per treated patient were estimated and a one-way sensitivity analysis was conducted to quantify the impact of parameter uncertainty on the model outcomes.

Results: Total cumulative costs per patient over 5 years were $834,621 for pdFVIII/VWF patients and $1,237,163 for rFVIII patients, representing a total saving of $402,542 per patient over the 5-year period, for an average annual saving of $80,508 per patient.

Conclusions: Based on data from the SIPPET study, this analysis found that initiating FVIII treatment in severe hemophilia A PUPs with pdFVIII/VWF has the potential to offer substantial cost savings to healthcare payers, amounting to a one-third reduction in costs.     

Cost-effectiveness analysis of clopidogrel versus aspirin in patients with atherothrombosis based on the CAPRIE trial

SUMMARY

Clopidogrel has been shown to reduce the secondary risk of ischaemic events in vascular disease compared to aspirin. This article compares the economics of the two drugs for this condition, by providing an incremental cost-effectiveness ratio (iCER) of clopidogrel versus aspirin, using Belgium as a case setting.

A 2 year Markov model, in which patients with vascular disease were assumed to receive either clopidogrel or aspirin, was developed from a healthcare payer's perspective. Survival data were based on the Saskatchewan Health database. Costs included treatment and adverse events. Cost-effectiveness was expressed as the cost per life year gained (LYG).

The iCER of clopidogrel versus aspirin was €13,390/LYG (95% CI: €6,990; €26,470). The robustness of these results was shown by univariate and probabilistic sensitivity analyses.

This analysis shows that clopidogrel is cost-effective for the secondary prevention of ischaemic events in the Belgian setting.     

Indirect comparison of the effects of anti-TNF biological agents in patients with Ankylosing Spondylitis by means of a Mixed Treatment Comparison performed on efficacy data from published randomised,controlled trials

Abstract

Objectives:

To compare ASAS (Assessment in Ankylosing Spondylitis Response Criteria), 20 response patterns between anti-TNF biological agents in patients with ankylosing spondylitis by means of a mixed treatment comparison of different randomized, controlled trials (RCTs) on the efficacy of biological therapies.

Methods:

A systematic review of literature was performed to identify a number of similarly designed double-blind, randomized, placebo-controlled trials investigating the efficacy of the TNF-α inhibitors etanercept, infliximab, and adalimumab in the treatment of ankylosing spondylitis patients, conducted over an 18-year period. The end-point of interest was ASAS20 response criteria at 24 weeks. Results were analyzed simultaneously using Bayesian mixed treatment comparison techniques. Results were expressed as odds ratio (OR) of ASAS20 response and associated 95% credible intervals (CrIs). The probability of being the best treatment was also reported.

Results:

Three RCTs were selected for data extraction and further analysis. By mean of MTC, all anti-TNF agents demonstrated to be more efficacious in inducing an ASAS20 response than placebo. Infliximab shows a 72% probability of being the best treatment of all. Adalimumab and etanercept show probabilities of 13% and 15%, respectively. No differences were observed when comparing directly an anti-TNF-α agent against another. When compared with placebo, Infliximab increases the probability of response by ～7-times (OR?=?6.8), Adalimumab by ～4-times (OR?=?4.4), and Etanercept by 5-times (OR?=?4.9). Differences in trials procedures, the use of a fixed-effect model, and the small number of trials included represent limitations of this study

Conclusions:

Even if the mixed treatment comparisons between infliximab, adalimumab, and etanercept did not show a statistically signi?cant difference, this analysis suggests that infliximab, compared to placebo, is expected to provide the highest rate of ASAS20 response in SA patients naive to biologic treatments.     

Comparison of treatment costs in inadequately controlled type 2 diabetes in Germany based on the APOLLO trial with insulin glargine

Abstract

Objective: A cost analysis of once-daily insulin glargine versus three-times daily insulin lispro in combination with oral antidiabetic drugs (OADs) for insulin-naive type 2 diabetes patients in Germany based on the APOLLO trial (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetes patients failing Oral treatment).

Methods: Annual direct treatment costs were estimated from the perspective of the German statutory health insurance (SHI). Costs accounted for included insulin medication, disposable pens and consumable items (needles, blood glucose test strips and lancets). Sensitivity analyses (on resource use and unit costs) were performed to reflect current German practice.

Results: Average treatment costs per patient per year in the base case were €1,073 for glargine and €1,794 for lispro. Insulin costs represented 65% vs. 37% of total costs respectively. Acquisition costs of glargine were offset by the lower costs of consumable items (€380 vs. €1,139). Sensitivity analyses confirmed the robustness of the results in favour of glargine. All scenarios yielded cost savings in total treatment costs ranging from €84 to €727.

Conclusions: Combination therapy of once-daily insulin glargine versus three-times daily insulin lispro both with OADs, in the management of insulin-dependent type 2 diabetes offers the potential for substantial cost savings from the German SHI perspective.     

基于VAR模型的广西保险发展与经济增长关联机制研究

改革开放30年以来,随着宏观经济的迅猛发展,广西保险业不断发展壮大。通过建立VAR模型,运用脉冲响应函数与方差分解的方法,分析了广西保险发展与宏观经济之间的关联机制。分析结果表明,广西保险发展与宏观经济增长之间存在明显的正相关关系;广西宏观经济增长是保险发展的Granger原因,但保险发展对宏观经济增长的作用不显著;广西宏观经济增长与保险发展之间的具体关联过程存在较大差异,人均可支配收入的增长对保险发展具有立竿见影的效果,而保险发展对经济增长的作用较为滞后,需经历两年的时滞后才开始发挥作用,且作用相对较弱。