Cost-Effectiveness of Single- versus Multiple-Inhaler Triple Therapy in a UK COPD Population: The INTREPID Trial.

Purpose: The 24-week INTREPID trial demonstrated the clinical benefits of once-daily single-inhaler triple therapy (SITT) with fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) versus non-ELLIPTA multiple-inhaler triple therapy (MITT) in patients with symptomatic chronic obstructive pulmonary disease (COPD). This analysis assessed the cost-effectiveness of FF/UMEC/VI versus non-ELLIPTA MITT for the treatment of symptomatic COPD from a United Kingdom (UK) National Health Service (NHS) perspective. Patients and Methods: The analysis was conducted using the validated GALAXY COPD disease progression model. Baseline characteristics, treatment effect parameters (forced expiratory volume in 1 second and St. George's Respiratory Questionnaire score [derived from exploratory COPD Assessment Test score mapping]), and discontinuation data from INTREPID were used to populate the model. UK healthcare resource and drug costs (2020 British pounds) were applied, and costs and outcomes were discounted at 3.5%. Analyses were conducted over a lifetime horizon from a UK NHS perspective. Model outputs included exacerbation rates, total costs, life years (LYs), quality-adjusted LYs (QALYs) and incremental cost-effectiveness ratio per QALY. Sensitivity analyses were conducted to assess the robustness of the results by varying parameter values and assumptions. Results: Over a lifetime horizon, FF/UMEC/VI provided an additional 0.174 (95% confidence interval [CI]: 0.024, 0.344) LYs (approximately 2 months), and 0.253 (95% CI: 0.167, 0.346) QALYs (approximately 3 months), at a cost saving of £1764 (95% CI: -£2600, -£678) per patient, compared with non-ELLIPTA MITT. FF/UMEC/VI remained the dominant treatment option, meaning greater benefits at lower costs, across all scenario and sensitivity analyses. Conclusion: Based on this analysis, in a UK setting, FF/UMEC/VI would improve health outcomes and reduce costs compared with non-ELLIPTA MITT for the treatment of patients with symptomatic COPD. SITT may help to reduce the clinical and economic burden of COPD and should be considered by physicians as a preferred treatment option.

Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis.

INTRODUCTION: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting ß2-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD. METHODS: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV1), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible). RESULTS: The NMA was informed by five trials reporting FEV1 at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV1 (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6). CONCLUSION: The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.

Economic Evaluation of Umeclidinium/Vilanterol versus Umeclidinium or Salmeterol in Symptomatic Non-Exacerbating Patients with COPD from a UK Perspective Using the GALAXY Model.

INTRODUCTION: Dual bronchodilators are recommended as maintenance treatment for patients with symptomatic COPD in the UK; further evidence is needed to evaluate cost-effectiveness versus monotherapy. Cost-effectiveness of umeclidinium/vilanterol versus umeclidinium and salmeterol from a UK healthcare perspective in patients without exacerbations in the previous year was assessed using post hoc EMAX trial data. METHODS: The validated GALAXY model was populated with baseline characteristics and treatment effects from the non-exacerbating subgroup of the symptomatic EMAX population (COPD assessment test score ≥10) and 2020 UK healthcare and drug costs. Outputs included estimated exacerbation rates, costs, life-years (LYs), and quality-adjusted LYs (QALYs); incremental cost-effectiveness ratio (ICER) was calculated as incremental cost/QALY gained. The base case (probabilistic model) used a 10-year time horizon, assumed no treatment discontinuation, and discounted future costs and QALYs by 3.5% annually. Sensitivity and scenario analyses assessed robustness of model results. RESULTS: Umeclidinium/vilanterol treatment was dominant versus umeclidinium and salmeterol, providing an additional 0.090 LYs (95% range: 0.035, 0.158) and 0.055 QALYs (-0.059, 0.168) with total cost savings of £690 (£231, £1306) versus umeclidinium, and 0.174 LYs (0.076, 0.286) and 0.204 QALYs (0.079, 0.326) with savings of £1336 (£1006, £2032) versus salmeterol. In scenario and sensitivity analyses, umeclidinium/vilanterol was dominant versus umeclidinium except over a 5-year time horizon (more QALYs at higher total cost; ICER=£4/QALY gained) and at the lowest estimate of the St George's Respiratory Questionnaire treatment effect (fewer QALYs at lower total cost; ICER=£12,284/QALY gained); umeclidinium/vilanterol was consistently dominant versus salmeterol. At willingness-to-pay threshold of £20,000/QALY, probability that umeclidinium/vilanterol was cost-effective in this non-exacerbating subgroup was 95% versus umeclidinium and 100% versus salmeterol. CONCLUSION: Based on model predictions from a UK perspective, symptomatic patients with COPD and no exacerbations in the prior year receiving umeclidinium/vilanterol are expected to have better outcomes at lower costs versus umeclidinium and salmeterol.

Lifetime Cost-effectiveness of Oral Semaglutide Versus Dulaglutide and Liraglutide in Patients With Type 2 Diabetes Inadequately Controlled With Oral Antidiabetics.

PURPOSE: To estimate the incremental cost-utility ratio of oral semaglutide (14 mg once daily) vs other glucagon-like peptide 1 receptor agonist treatments among adults with type 2 diabetes that was inadequately controlled with 1 to 2 oral antidiabetic drugs from a US payer perspective. METHODS: A state-transition model with a competing risk approach was developed for diabetic complications and risk of cardiovascular events based on the UK Prospective Diabetes Study Outcomes Model 1 equations. Baseline population characteristics reflect the PIONEER 4 trial (Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus) of oral semaglutide. Model comparators included subcutaneous semaglutide, dulaglutide, and liraglutide. Treatment effects (change in glycosylated hemoglobin, weight, and systolic blood pressure) were estimated by network meta-analysis. Drug, management, and event costs (in 2019 US dollars), survival after nonfatal events, and utilities were obtained from the literature. Costs and quality-adjusted life-year (QALY) outcomes were discounted at 3% annually over a lifetime horizon. Probabilistic and 1-way sensitivity analyses were performed. FINDINGS: Total estimated costs and QALYs were $144,065 and 12.98 for oral semaglutide, $145,721 and 12.96 for dulaglutide, $145,833 and 12.99 for SC semaglutide, and $149,428 and 12.97 for liraglutide, respectively. Oral semaglutide was less costly and more effective than dulaglutide and liraglutide but less costly than subcutaneous semaglutide with similar effectiveness. Oral semaglutide was favored versus subcutaneous semaglutide in 52.10% of model replications at a willingness-to-pay of $150,000 per QALY. IMPLICATIONS: Oral semaglutide is predicted to offer health benefits similar to subcutaneous semaglutide and ahead of dulaglutide and liraglutide. Oral semaglutide is a cost-effective glucagon-like peptide 1 receptor agonist treatment option.

Cost-effectiveness and budget impact of liraglutide in type 2 diabetes patients with elevated cardiovascular risk: a US-managed care perspective.

BACKGROUND: The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcomes Results (LEADER) clinical trial demonstrated that liraglutide added to standard-of-care (SoC) therapy for type 2 diabetes (T2D) with established cardiovascular disease (CVD) or elevated cardiovascular (CV) risk was associated with lower rates of death from CVD, nonfatal myocardial infarction (MI), or nonfatal stroke than SoC alone. OBJECTIVE: The objective of this study was to assess the cost-effectiveness (CE) and budget impact of liraglutide vs SoC in T2D patients with established CVD or elevated CV risk, over a lifetime horizon from a US managed care perspective. METHODS: A cohort state-transition model (costs and benefits discounted at 3% per year) was used to predict diabetes-related complications and death (CV and all-cause). Events, treatment effects, and discontinuation rates were from LEADER trial; utility and cost data (US$, 2017) were from literature. Sensitivity analysis explored the impact of uncertainty on results. Additionally, a budget impact analysis was conducted to evaluate the financial impact of liraglutide use in this population, with displacement from dulaglutide, assuming a health care plan with 1 million members. RESULTS: Liraglutide patients experienced 6.3% fewer events, had event-related cost-savings of $15,182, gained additional life-years of 0.67 and quality-adjusted life-years (QALYs) of 0.57, and had additional total costs ($60,928) vs SoC. Liraglutide was cost-effective with an incremental CE ratio of $106,749/QALY which was below the willingness-to-pay threshold of $150,000/QALY accepted by the Institute of Clinical and Economic Research. Liraglutide was cost-effective across all sensitivity analyses, except when the hazard ratio for all-cause mortality varied. The budget impact was neutral, with a per-plan-per-year and per-member-per-month cost-savings of $266,334 and $0.02, respectively. CONCLUSION: From a US-managed care perspective, for T2D patients with established CVD or elevated CV risk, liraglutide is a cost-effective and a budget neutral treatment option for health care plans.

Prediction models for exacerbations in different COPD patient populations: comparing results of five large data sources.

BACKGROUND AND OBJECTIVES: Exacerbations are important outcomes in COPD both from a clinical and an economic perspective. Most studies investigating predictors of exacerbations were performed in COPD patients participating in pharmacological clinical trials who usually have moderate to severe airflow obstruction. This study was aimed to investigate whether predictors of COPD exacerbations depend on the COPD population studied. METHODS: A network of COPD health economic modelers used data from five COPD data sources - two population-based studies (COPDGene® and The Obstructive Lung Disease in Norrbotten), one primary care study (RECODE), and two studies in secondary care (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoint and UPLIFT) - to estimate and validate several prediction models for total and severe exacerbations (= hospitalization). The models differed in terms of predictors (depending on availability) and type of model. RESULTS: FEV1% predicted and previous exacerbations were significant predictors of total exacerbations in all five data sources. Disease-specific quality of life and gender were predictors in four out of four and three out of five data sources, respectively. Age was significant only in the two studies including secondary care patients. Other significant predictors of total exacerbations available in one database were: presence of cough and wheeze, pack-years, 6-min walking distance, inhaled corticosteroid use, and oxygen saturation. Predictors of severe exacerbations were in general the same as for total exacerbations, but in addition low body mass index, cardiovascular disease, and emphysema were significant predictors of hospitalization for an exacerbation in secondary care patients. CONCLUSIONS: FEV1% predicted, previous exacerbations, and disease-specific quality of life were predictors of exacerbations in patients regardless of their COPD severity, while age, low body mass index, cardiovascular disease, and emphysema seem to be predictors in secondary care patients only.

Once-Daily Triple Therapy in Patients with Advanced COPD: Healthcare Resource Utilization Data and Associated Costs from the FULFIL Trial.

INTRODUCTION: Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden. Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study. Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg. METHODS: FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study. Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs. RESULTS: Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%). Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs. 32.7%). Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs. £763.32 and £749.22 vs. £988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs. £1,267.45). CONCLUSIONS: This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02345161. FUNDING: GSK.

Development of the Galaxy Chronic Obstructive Pulmonary Disease (COPD) Model Using Data from ECLIPSE: Internal Validation of a Linked-Equations Cohort Model.

BACKGROUND: The recent joint International Society for Pharmacoeconomics and Outcomes Research / Society for Medical Decision Making Modeling Good Research Practices Task Force emphasized the importance of conceptualizing and validating models. We report a new model of chronic obstructive pulmonary disease (COPD) (part of the Galaxy project) founded on a conceptual model, implemented using a novel linked-equation approach, and internally validated. METHODS: An expert panel developed a conceptual model including causal relationships between disease attributes, progression, and final outcomes. Risk equations describing these relationships were estimated using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, with costs estimated from the TOwards a Revolution in COPD Health (TORCH) study. Implementation as a linked-equation model enabled direct estimation of health service costs and quality-adjusted life years (QALYs) for COPD patients over their lifetimes. Internal validation compared 3 years of predicted cohort experience with ECLIPSE results. RESULTS: At 3 years, the Galaxy COPD model predictions of annual exacerbation rate and annual decline in forced expiratory volume in 1 second fell within the ECLIPSE data confidence limits, although 3-year overall survival was outside the observed confidence limits. Projections of the risk equations over time permitted extrapolation to patient lifetimes. Averaging the predicted cost/QALY outcomes for the different patients within the ECLIPSE cohort gives an estimated lifetime cost of £25,214 (undiscounted)/£20,318 (discounted) and lifetime QALYs of 6.45 (undiscounted/5.24 [discounted]) per ECLIPSE patient. CONCLUSIONS: A new form of model for COPD was conceptualized, implemented, and internally validated, based on a series of linked equations using epidemiological data (ECLIPSE) and cost data (TORCH). This Galaxy model predicts COPD outcomes from treatment effects on disease attributes such as lung function, exacerbations, symptoms, or exercise capacity; further external validation is required.

Statistical Modeling of Disease Progression for Chronic Obstructive Pulmonary Disease Using Data from the ECLIPSE Study.

BACKGROUND: To develop statistical models predicting disease progression and outcomes in chronic obstructive pulmonary disease (COPD), using data from ECLIPSE, a large, observational study of current and former smokers with COPD. METHODS: Based on a conceptual model of COPD disease progression and data from 2164 patients, associations were made between baseline characteristics, COPD disease progression attributes (exacerbations, lung function, exercise capacity, and symptoms), health-related quality of life (HRQoL), and survival. Linear and nonlinear functional forms of random intercept models were used to characterize these relationships. Endogeneity was addressed by time-lagging variables in the regression models. RESULTS: At the 5% significance level, an exacerbation history in the year before baseline was associated with increased risk of future exacerbations (moderate: +125.8%; severe: +89.2%) and decline in lung function (forced expiratory volume in 1 second [FEV1]) (-94.20 mL per year). Each 1% increase in FEV1 % predicted was associated with decreased risk of exacerbations (moderate: -1.1%; severe: -3.0%) and increased 6-minute walk test distance (6MWD) (+1.5 m). Increases in baseline exercise capacity (6MWD, per meter) were associated with slightly increased risk of moderate exacerbations (+0.04%) and increased FEV1 (+0.62 mL). Symptoms (dyspnea, cough, and/or sputum) were associated with an increased risk of moderate exacerbations (+13.4% to +31.1%), and baseline dyspnea (modified Medical Research Council score ≥2 v. <2) was associated with lower FEV1 (-112.3 mL). CONCLUSIONS: A series of linked statistical regression equations have been developed to express associations between indicators of COPD disease severity and HRQoL and survival. These can be used to represent disease progression, for example, in new economic models of COPD.

Cost-effectiveness of switching to exemestane versus continued tamoxifen as adjuvant therapy for postmenopausal women with primary breast cancer.

BACKGROUND: Sequential tamoxifen/exemestane therapy reportedly improves disease-free survival in women with primary breast cancer compared with continued tamoxifen therapy. The objective of the current study was to assess the cost-effectiveness of switching to exemestane after 2 to 3 years of tamoxifen versus continued tamoxifen in postmenopausal women with primary breast cancer for a total of 5 years of adjuvant therapy. METHODS: A Markov model based on the Intergroup Exemestane Study (IES) population compared switching to exemestane versus continued tamoxifen for 2.5 years of therapy and 5 years of postadjuvant therapy follow-up. Disease progression and hazards ratios (HR) for recurrence and survival were determined from datasets (IES and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute) and from the published literature. An expert panel validated treatment patterns, outcomes, and resource utilization. Direct medical costs were included based on published sources. Cost-effectiveness ratios were determined, and extensive sensitivity analyses were conducted. RESULTS: Exemestane was found to be more effective than tamoxifen alone with regard to disease-free survival (2.6% absolute improvement), life-years gained (0.1028 LY), and quality-adjusted life-years gained (0.1195 QALY), at an additional cost of 2,889 Can dollars per person over 7.5 years. Incremental cost-effectiveness ratios were 28,119 Can dollars/LY gained and 24,185 Can dollars/QALY gained. The model was most sensitive to distant recurrence HR but was robust to variations in clinical, cost, and utility parameters. CONCLUSIONS: Switching to adjuvant exemestane after 2 to 3 years of tamoxifen is cost-effective in postmenopausal women with primary breast cancer.

Economic evaluation of oseltamivir phosphate for postexposure prophylaxis of influenza in long-term care facilities.

OBJECTIVES: To compare the cost-effectiveness of oseltamivir postexposure prophylaxis during influenza A outbreaks with that of amantadine postexposure prophylaxis or no postexposure prophylaxis in long-term care facilities (LTCFs). DESIGN: Cost-effectiveness analysis based on decision analytic model from a government-payer perspective. SETTING: A Canadian LTCF, with high staff vaccination, at the beginning of influenza season. PARTICIPANTS: Elderly, influenza-vaccinated patients living in a Canadian LTCF. MEASUREMENTS: Incremental costs (or savings) per influenza-like illness case avoided compared with usual care. RESULTS: From a government-payer perspective, this analysis showed that oseltamivir was a dominant strategy because it was associated with the fewest influenza-like illness cases, with cost savings of $1,249 per 100 patients in 2001 Canadian dollars compared with amantadine and $3,357 per 100 patients compared with no prophylaxis. Costs for amantadine dose calculation and hospitalization for adverse events contributed to amantadine being a more-expensive prophylaxis strategy than oseltamivir. Both prophylaxis strategies were more cost-effective than no prophylaxis. CONCLUSION: Despite high influenza vaccination rates, influenza outbreaks continue to emerge in LTCFs, necessitating cost-effective measures to further limit the spread of influenza and related complications. Although amantadine has a lower acquisition cost than oseltamivir, it is associated with more adverse events, lower efficacy, and individualized dosing requirements, leading to higher overall costs and more influenza-like illness cases than oseltamivir. Therefore the use of oseltamivir postexposure prophylaxis is more cost-effective than the current standard of care with amantadine prophylaxis or no prophylaxis.