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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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      Modelling the Cost-Effectiveness of Indacaterol/Glycopyrronium versus Salmeterol/Fluticasone Using a Novel Markov Exacerbation-Based Approach

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          Abstract

          Purpose

          Exacerbations drive outcomes and costs in chronic obstructive pulmonary disease (COPD). While patient-level (micro) simulation cost-effectiveness models have been developed that include exacerbations, such models are complex. We developed a novel, exacerbation-based model to assess the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in COPD, using a Markov structure as a simplification of a previously validated microsimulation model.

          Methods

          The Markov model included three health states: infrequent or frequent exacerbator (IE or FE; ≤1 or ≥2 moderate/severe exacerbations in prior 12 months, respectively), or death. The model used data from the FLAME study and was run over a 10-year horizon. Cycle length was 1 year, after which patients remained in the same health state or transitioned to another. Analysis was conducted from a Swedish payer’s perspective (Swedish healthcare costs, converted into Euros), with incremental costs and quality-adjusted life-years (QALYs) calculated (discounted 3% annually).

          Results

          At all post-baseline timepoints, IND/GLY was associated with more patients in the IE health state and fewer patients in the FE and dead states relative to SFC. Over a 10-year period, IND/GLY was associated with a cost saving of €1,887/patient, an incremental benefit of 0.142 QALYs, and an addition of 0.057 life-years, compared with SFC.

          Conclusion

          This Markov model represents a novel cost-effectiveness analysis for COPD, with simpler methodology than prior microsimulation models, while retaining exacerbations as drivers of disease progression. In patients with COPD with a history of exacerbations in the previous year, IND/GLY is a cost-effective treatment option compared with SFC.

          Most cited references36

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease. The Lung Health Study.

            Previous studies of lung function in relation to smoking cessation have not adequately quantified the long-term benefit of smoking cessation, nor established the predictive value of characteristics such as airway hyperresponsiveness. In a prospective randomized clinical trial at 10 North American medical centers, we studied 3, 926 smokers with mild-to-moderate airway obstruction (3,818 with analyzable results; mean age at entry, 48.5 yr; 36% women) randomized to one of two smoking cessation groups or to a nonintervention group. We measured lung function annually for 5 yr. Participants who stopped smoking experienced an improvement in FEV(1) in the year after quitting (an average of 47 ml or 2%). The subsequent rate of decline in FEV(1) among sustained quitters was half the rate among continuing smokers, 31 +/- 48 versus 62 +/- 55 ml (mean +/- SD), comparable to that of never-smokers. Predictors of change in lung function included responsiveness to beta-agonist, baseline FEV(1), methacholine reactivity, age, sex, race, and baseline smoking rate. Respiratory symptoms were not predictive of changes in lung function. Smokers with airflow obstruction benefit from quitting despite previous heavy smoking, advanced age, poor baseline lung function, or airway hyperresponsiveness.
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              Does quality of life of COPD patients as measured by the generic EuroQol five-dimension questionnaire differentiate between COPD severity stages?

              To assess the discriminative properties of the EuroQol five-dimension questionnaire (EQ-5D) with respect to COPD severity according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria in a large multinational study. Baseline EQ-5D visual analog scale (VAS) scores, EQ-5D utility scores, and St. George Respiratory Questionnaire scores were obtained from a subset of patients in the Understanding the Potential Long-term Impact on Function with Tiotropium trial, which was a 4-year placebo-controlled trial designed to assess the effect of tiotropium on the rate of decline in FEV(1) in COPD patients aged > or = 40 years, an FEV(1) of /= 10 pack-years. A total of 1,235 patients (mean post bronchodilator FEV(1), 48.8% predicted) from 13 countries completed the EQ-5D. The EQ-5D VAS and utility scores differed significantly among patients in GOLD stages 2, 3, and 4, also after correction for age, sex, smoking, body mass index (BMI), and comorbidity (p < 0.001). The mean EQ-5D VAS scores for patients in GOLD stages 2, 3, and 4 were 68 (SD, 16), 62 (SD, 17), and 58 (SD, 16), respectively. The mean utility scores were 0.79 (SD, 0.20) for patients in GOLD stage 2, 0.75 (SD, 0.21) for patients in GOLD stage 3, and 0.65 (SD, 0.23) for patients in GOLD stage 4. Effect sizes for the difference in utility scores between patients in GOLD stages 3 and 4 were more than twice as high as those for the difference between patients in GOLD stages 2 and 3. Gender, postbronchodilator FEV(1) percent predicted, the number of hospital admissions and emergency department visits in the year prior to baseline measurements, measures of comorbidity, and BMI were independently associated with EQ-5D utility. EQ-5D utility scores also differed between patients from different countries. French patients especially had lower utility scores than US patients. Utility scores calculated with the US value set were on average 5% higher than those calculated with the UK value set. Increasing severity of COPD was associated with a significant decline in EQ-5D VAS scores and utility scores. These results demonstrate that a generic instrument can assess COPD impact on quality of life and that the scores discriminate between patient groups of known severity. These utility scores will be useful in cost-effectiveness assessments.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                COPD
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                16 April 2020
                2020
                : 15
                : 787-797
                Affiliations
                [1 ]Novartis Ireland Limited , Dublin, Ireland
                [2 ]Novartis Pharma , Basel, AG, Switzerland
                [3 ]PT Health Economics Ltd , Sheffield, UK
                Author notes
                Correspondence: Ronan Mahon Team Head, Patient Access Services Product Lifecycle Services – Novartis Global Service Center Dublin , Vista Building, Elm Park Business Campus, Dublin4, IrelandTel +353873647443 Email ronan.mahon@novartis.com
                Author information
                http://orcid.org/0000-0001-7754-5744
                http://orcid.org/0000-0003-4501-2083
                Article
                247156
                10.2147/COPD.S247156
                7174156
                e6312de8-72e4-49ce-99c6-5a4aede64fa2
                © 2020 Lakhotia et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 24 January 2020
                : 30 March 2020
                Page count
                Figures: 3, Tables: 2, References: 53, Pages: 11
                Funding
                This study was funded by Novartis Pharma AG (Basel, Switzerland).
                Categories
                Original Research

                Respiratory medicine
                chronic obstructive pulmonary disease,indacaterol/glycopyrronium,cost-effective,exacerbation,markov model

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