fluticasone-propionate--salmeterol-xinafoate-drug-combination and Pulmonary-Disease--Chronic-Obstructive

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Drugs, Generic; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Health Services Needs and Demand; Humans; Nebulizers and Vaporizers; Powders; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Standard of Care; Therapeutic Equivalency

This review identifies and evaluates the comprehensive reporting of peer-reviewed economic evaluations of the effectiveness of fluticasone-propionate/salmeterol combination (FSC) therapy for maintenance treatment of chronic obstructive pulmonary disease (COPD). Economic evaluations were included if published in English since 2003. Evaluation categories included in the review were cost-effectiveness, cost-utility, and cost-consequence analyses. FSC is cost-effective in comparison to short-acting bronchodilators (SABDs). Cost and outcome differences between FSC and other long-acting therapies were modest. Studies exhibited large variations in populations, designs and environment, limiting the ability to draw conclusions. Many new maintenance treatments for COPD have been approved since 2010. Most have yet to be compared to older treatments like FSC. Evaluations are needed that consider costs and outcomes from a societal perspective (e.g., patients' ability to keep working) and evaluations that include subgroup analyses to investigate differential impacts according to clusters of patient characteristics.

Topics: Bronchodilator Agents; Cost-Benefit Analysis; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

COPD guidelines recommend the combined use of inhaled long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) if symptoms are not improved by a single agent. This systematic review tested the hypothesis that the bronchodilator effect of the LABA/LAMA combination, umeclidinium (UMEC)/vilanterol (VIL), would translate into better outcomes without incurring increased adverse events (AEs).. This was a systematic review of randomized, placebo-controlled or crossover trials (> 4 weeks) involving UMEC/VIL compared with its monocomponents, tiotropium, or fluticasone/salmeterol. Primary outcomes were trough FEV1, serious adverse events (SAEs), and serious cardiovascular events (SCVEs).. Eleven trials from 10 studies (9,609 patients) showed that UMEV/VIL provided superior improvements in lung function compared with UMEC, VIL, tiotropium, and fluticasone propionate/salmeterol (mean trough FEV1, 60, 110, 90, and 90 mL, respectively; P < .0001). Also, UMEC/VIL had a greater likelihood of demonstrating a minimal clinically important difference on the Transition Dyspnea Index compared with UMEC and VIL (number needed to treat for benefit [NNTB] = 14 and 10, respectively). UMEC/VIL therapy significantly reduced the risk of COPD exacerbations compared with UMEC and VIL (NNTB = 42 and 41, respectively). On the contrary, we noted no significant differences between UMEC/VIL and tiotropium with respect to dyspnea, health status, or risk of COPD exacerbation. Regarding safety issues, the incidence of AEs, SAEs, SCVEs, and mortality on treatment was similar across treatments, suggesting reduced safety concerns with the use of the UMEC/VIL combination.. Once-daily inhaled UMEC/VIL showed superior efficacy compared with its monocomponents, tiotropium, and fluticasone/combination in patients with moderate to severe COPD.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Benzyl Alcohols; Chlorobenzenes; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg is a once-daily inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment approved in the United States, Canada and Europe for the long-term maintenance therapy of COPD. We report data from mixed treatment comparisons (MTC) of once-daily FF/VI against established twice-daily ICS/LABA combination therapies on clinical efficacy outcomes.. Data from 33 parallel-group randomised controlled trials (RCTs) of ICS/LABAs, of ≥8 weeks' duration in patients ≥12 years of age with COPD, identified by systematic review, were analysed using covariate-adjusted Bayesian hierarchical models for three efficacy outcomes. Lung function, assessed by change from baseline in forced expiratory volume in one second (FEV1), was the outcome of primary interest (n = 28 studies). Secondary objectives were assessment of annual rate of moderate/severe exacerbations (n = 15) and patient-reported health status, measured by change from baseline in St George's Respiratory Questionnaire (SGRQ) Total score (n = 20). Overall, 25 different treatments were included in the MTC; we report findings, including probabilities of non-inferiority, for comparisons of once-daily FF/VI 100/25 mcg with twice-daily fluticasone propionate (FP)/salmeterol (SAL) 500/50 mcg and budesonide (BUD)/formoterol (FORM) 400/12 mcg.. For FEV1, FF/VI 100/25 mcg demonstrated >99% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg using a 50 mL margin. For annual rate of moderate/severe exacerbations, FF/VI 100/25 mcg demonstrated 73% and 77% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg, respectively, using a 10% rate ratio margin. For SGRQ Total score, the corresponding probabilities of non-inferiority were 99% and 98%, respectively, on a 2-unit margin. Significant covariate effects were identified: increased age was associated with deterioration in FEV1 and reduced exacerbation frequency; shorter study duration was associated with reduced exacerbation frequency.. FF/VI 100/25 mcg was comparable with corresponding doses of FP/SAL and BUD/FORM on lung function and health status outcomes. Non-inferiority on moderate/severe exacerbation rate was not demonstrated to the same degree of confidence, though observed rates were similar. Model limitations include a weak treatment network for the exacerbation analysis and variability across the included studies. Our data support previous RCT findings suggesting that the efficacy of FF/VI 100/25 mcg on lung function and health status in COPD is comparable with twice-daily ICS/LABAs.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Androstadienes; Bayes Theorem; Benzyl Alcohols; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Disease Progression; Drug Administration Schedule; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Time Factors; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) and asthma are common airway disorders characterized by chronic airway inflammation and airflow obstruction, and are a leading cause of morbidity and mortality in the People's Republic of China. These two diseases pose a high economic burden on the family and the whole of society. Despite evidence-based Global Initiative for Chronic Obstructive Lung Disease and Global Initiative for Asthma guidelines being available for the diagnosis and management of COPD and asthma, many of these patients are not properly diagnosed or managed in the People's Republic of China. The value of combination therapy with inhaled corticosteroids and long-acting β2-agonists has been established in the management of asthma and COPD globally. Combinations of inhaled corticosteroids and long-acting β2-agonists such as fluticasone and salmeterol, have been shown to be effective for improving symptoms, health status, and reducing exacerbations in both diseases. In this review, we discuss the efficacy and safety of this combination therapy from key studies, particularly in the People's Republic of China.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Asian People; Asthma; Bronchodilator Agents; China; Cost-Benefit Analysis; Drug Costs; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Lung; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD, however, is a heterogeneous collection of diseases with differing causes, pathogenic mechanisms, and physiological effects. Therefore a comprehensive approach to COPD prevention will need to address the complexity of COPD. Advances in the understanding of the natural history of COPD and the development of strategies to assess COPD in its early stages make prevention a reasonable, if ambitious, goal.

Topics: Albuterol; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Disease Progression; Drug Combinations; Early Diagnosis; Early Medical Intervention; Exercise Test; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Severity of Illness Index; Smoking Cessation

Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients. Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers.. A systematic review was conducted to identify RCTs of COPD treatments reporting mortality; evidence was synthesised using network meta-analysis (NMA). The analysis included 40 RCTs; a quantitative indirect comparison between 14 treatments using data from 55,220 patients was conducted.. The analysis reported two treatments reducing all-cause mortality; salmeterol/fluticasone propionate combination (SFC) was associated with a reduction in mortality versus placebo in the fixed effects (HR 0.79; 95 % Crl 0.67, 0.94) but not the random effects model (0.79; 0.56, 1.09). Indacaterol was associated with a reduction in mortality versus placebo in fixed (0.28; 0.08 to 0.85) and random effects (0.29; 0.08, 0.89) models. Mean estimates and credible intervals for hazard ratios for indacaterol versus placebo are based on a small number of events; estimates may change when the results of future studies are included. These results were maintained across a variety of assumptions and provide evidence that SFC and indacaterol may lead to improved survival in COPD patients.. Results of an NMA of COPD treatments suggest that SFC and indacaterol may reduce mortality. Further research is warranted to strengthen this conclusion.

Topics: Albuterol; Aminopyridines; Beclomethasone; Benzamides; Benzyl Alcohols; Bronchodilator Agents; Budesonide; Chlorobenzenes; Cyclopropanes; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Indans; Ipratropium; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Quinolones; Survival Rate; Theophylline; Tiotropium Bromide; Triamcinolone

This meta-analysis was performed to evaluate the efficacy and safety of adding fluticasone propionate/salmeterol (FSC) to tiotropium (Tio) in COPD patients.. A systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases, and a hand search of leading respiratory journals. Randomized clinical trials on treatment of stable COPD with the addition of FSC, compared with tiotropium alone, were reviewed. Studies were pooled to odds ratio (OR) and weighted mean differences (WMD), with 95% confidence interval (CI).. Six trials met the inclusion criteria. Compared with tiotropium, addition of FSC presented significant effects on trough forced expiratory volume in 1s (FEV1) (WMD 54.64 mL; 95% CI 51.76 to 57.52 mL; P<0.001), COPD exacerbations (OR 0.73; 95% CI 0.55 to 0.96; p=0.03), and health-related quality of life (WMD 4.63; 95% CI 4.26 to 5.01; P<0.001). No significant increase was noticed in adverse events in the Tio+FSC group (OR 1.24; 95% CI 0.98 to 1.57; p=0.07).. The addition of FSC to subjects with COPD treated with tiotropium significantly improves lung function, quality of life and COPD exacerbations without increasing the risk of adverse events.

Topics: Albuterol; Androstadienes; Disease Progression; Drug Combinations; Drug Therapy, Combination; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Current clinical guidelines recommend long-acting bronchodilators as the mainstay of the pharmacotherapy of patients with chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS), in conjunction with long-acting beta-agonists (LABA), are routinely considered at severe and very severe stages of COPD when patients lack adequate response to single-therapy with LABAs. Although the study methodologies evaluating the clinical effectiveness of the combination therapy using salmeterol and fluticasone (SAL/FLU) for patients with COPD have been questioned, a number of studies have suggested that using ICS, in combination with a LABA agent, may improve survival of patients with COPD.. This article attempts to review the most current evidence for using SAL/FLU in the management of COPD and summarizes the results of outcome measures reported in randomized controlled trials.. Until new forms of drug combinations are made available, the use of dual-therapy containing a LABA and ICS remain as the most logical and appropriate approach for the treatment of patients suffering from severe and very severe COPD with repeated exacerbations.

Topics: Albuterol; Androstadienes; Costs and Cost Analysis; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Pulmonary Disease, Chronic Obstructive

Both long-acting beta(2)-agonists and inhaled corticosteroids have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease (COPD). Their co-administration in a combined inhaler is intended to facilitate adherence to medication regimens and to improve efficacy. Three preparations are currently available: fluticasone propionate/salmeterol (FPS). budesonide/formoterol (BDF) and mometasone furoate/formoterol (MF/F).. To assess the efficacy and safety of combined long-acting beta2-agonist and inhaled corticosteroid (LABA/ICS) preparations, as measured by clinical endpoints and pulmonary function testing, compared with inhaled corticosteroids (ICS) alone, in the treatment of adults with chronic obstructive pulmonary disease (COPD).. We searched the Cochrane Airways Group Specialised Register of trials, which is compiled from systematic searches of multiple literature databases. The search was conducted in June 2013. In addition, we checked the reference lists of included studies and contacted the relevant manufacturers.. Studies were included if they were randomised and double-blind. Compared studies combined LABA/ICS with the ICS component.. Two review authors independently assessed trial quality and extracted data. The primary outcomes were exacerbations, mortality and pneumonia. Health-related quality of life (as measured by validated scales), lung function and side effects were secondary outcomes. Dichotomous data were analysed as fixed-effect odds ratios with 95% confidence intervals (CIs), and continuous data as mean differences or rate ratios and 95% CIs.. A total of 15 studies of good methodological quality met the inclusion criteria by randomly assigning 7814 participants with predominantly poorly reversible, severe COPD. Data were most plentiful for the FPS combination. Exacerbation rates were significantly reduced with combination therapies (rate ratio 0.87, 95% CI 0.80 to 0.94, 6 studies, N = 5601) compared with ICS alone. The mean exacerbation rate in the control (ICS) arms of the six included studies was 1.21 exacerbations per participant per year (range 0.88 to 1.60), and we would expect this to be reduced to a rate of 1.05 (95% CI 0.97 to 1.14) among those given combination therapy. Mortality was also lower with the combination (odds ratio (OR) 0.78, 95% CI 0.64 to 0.94, 12 studies, N = 7518) than with ICS alone, but this was heavily weighted by a three-year study of FPS. When this study was removed, no significant mortality difference was noted. The reduction in exacerbations did not translate into significantly reduced rates of hospitalisation due to COPD exacerbation (OR 0.93, 95% CI 0.80 to 1.07, 10 studies, N = 7060). Lung function data favoured combination treatment in the FPS, BDF and MF/F trials, but the improvement was small. Small improvements in health-related quality of life were measured on the St George's Respiratory Questionnaire (SGRQ) with FPS or BDF compared with ICS, but this was well below the minimum clinically important difference. Adverse event profiles were similar between the two treatments arms, and rates of pneumonia when it was diagnosed by chest x-ray (CXR) were lower than those reported in earlier trials.. Combination ICS and LABA offer some clinical benefits in COPD compared with ICS alone, especially for reduction in exacerbations. This review does not support the use of ICS alone when LABAs are available. Adverse events were not significantly different between treatments. Further long-term assessments using practical outcomes of current and new 24-hour LABAs will help determine their efficacy and safety. For robust comparisons as to their relative effects, long-term head-to-head comparisons are needed.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Pneumonia; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Steroids

The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials.. Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)) and transitional dyspnea index at 12 weeks.. Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV(1) at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (-0.49 points [-1.87-0.89]).. Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function. In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Dyspnea; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Indans; Outcome Assessment, Health Care; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic

To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).. Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg (n = 1). Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)), total scores for St. George's Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.. Indacaterol 150 μg resulted in a higher change from baseline (CFB) in FEV(1) at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 μg (0.02 L [-0.04, 0.08]) and SAL/FP 50/500 μg (0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 μg at 12 weeks and indacaterol 150/300 μg at 6 months. Indacaterol 150 μg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 μg (-2.16 point improvement [-4.96, 0.95]). Indacaterol 150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21 points (-0.57, 0.99); 0.39 [-0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6 months.. Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of lung function. Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 μg) and SAL/FP 50/500 μg in terms of health status and to SAL/FP (50/250 and 50/500 μg) in terms of breathlessness.

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Indans; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Treatment Outcome

Exacerbations contribute significantly to the morbidity of COPD, leading to an accelerated decline in lung function, reduced functional status, reduced health status and quality of life, poorer prognosis and increased mortality. Prevention of exacerbations is thus an important goal of COPD management. In patients with COPD, treatment with a combination of the inhaled corticosteroid fluticasone propionate (250 microg) and the long-acting beta(2)-agonist salmeterol (50 microg) in a single inhaler (250/50 microg) is an effective therapy option that has been shown to reduce the frequency of exacerbations, to improve lung function, dyspnea and health status, and to be relatively cost-effective as a COPD maintenance therapy. Importantly, results of various studies suggest that fluticasone propionate and salmeterol have synergistic effects when administered together that improve their efficacy in controlling symptoms and reducing exacerbations. The present non-systematic review summarizes the role of fluticasone propionate/salmeterol combination therapy in the prevention of exacerbations of COPD and its related effects on lung function, survival, health status, and healthcare costs.

Topics: Albuterol; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

Influencing the progression of COPD has long been an elusive goal of drug therapy. Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT). Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced. The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD. The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease. With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted.

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Cholinergic Antagonists; Disease Progression; Double-Blind Method; Drug Combinations; Evidence-Based Medicine; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Scopolamine Derivatives; Severity of Illness Index; Time Factors; Tiotropium Bromide; Treatment Outcome

The costs of asthma and chronic obstructive pulmonary disease (COPD), the two most common chronic respiratory illnesses, are substantial and rising. The fixed-dose combination of fluticasone and salmeterol has been a safe and effective therapy for these diseases.. To review the pharmacoeconomic impact of the fixed-dose combination of inhaled fluticasone and salmeterol in asthma and COPD.. A systematic review of the literature was carried out to identify pharmacoeconomic studies with fixed-dose salmeterol and fluticasone (Seretide, Advair, Viani). In addition, abstracts from recent respiratory meetings were sought, and any unpublished data were requested from the manufacturer.. For asthma, when compared to treatment with inhaled corticosteroid monotherapy and antileukotrienes, alone or combined, salmeterol/fluticasone inhalation produced a higher proportion of successfully treated weeks, improvement in lung function and quality of life, and fewer treatment failures. The costs per quality-adjusted life year (QALY) for fluticasone/salmeterol have been favourable not only in patients with moderate to severe disease but also in patients with mild disease or patients not previously treated with a maintenance therapy. The excess cost per QALY varied from US$2,670 to US$26,445. For COPD, a clear reduction in exacerbation rates and improvement in quality of life has been demonstrated with salmeterol/fluticasone along with a likely improvement in survival rates. The incremental cost per QALY ratio for fluticasone/salmeterol against placebo ranged from US$9,512 to US$64,038.. The data currently available suggest that the cost effectiveness of combination therapy with fluticasone and salmeterol is favourable for asthma and COPD in a variety of clinical settings.

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Quality-Adjusted Life Years

Inhaled corticosteroids with or without long-acting beta2 adrenergic agonists are commonly used to treat patients with chronic obstructive pulmonary disease to attenuate symptoms and to prevent exacerbations. Whether these medications prolong survival is uncertain.. Inhaled corticosteroids attenuate airway and systemic inflammation, reduce airway hyperreactivity, improve patient symptoms and prevent exacerbations in chronic obstructive pulmonary disease patients. The data on mortality are mixed. A pooled analysis of published randomized controlled trials indicated that inhaled corticosteroids reduced mortality by around 25%; however other studies have failed to show a beneficial effect on mortality. The addition of long-acting beta2 adrenergic agonists to inhaled corticosteroids enhances the clinical effectiveness of these medications and confers incremental mortality benefits to patients. Interestingly, these medications appear to be especially beneficial in reducing cardiovascular morbidity and mortality, though large randomized controlled trials powered specifically on these endpoints are needed to confirm these early findings.. Inhaled corticosteroids, especially with long-acting beta2 adrenergic agonists, reduce airway inflammation and appear to prolong survival in chronic obstructive pulmonary disease patients. They may be particularly effective in reducing cardiovascular morbidity and mortality of patients, pending confirmation by additional clinical studies powered specifically on these endpoints.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Survival Analysis

Salmeterol/fluticasone propionate (Seretide, Advair, Viani) administered using a multidose dry powder inhaler (Diskus, Accuhaler) is approved for use in the treatment of chronic obstructive pulmonary disease (COPD) in numerous countries.Salmeterol/fluticasone propionate administered twice daily via dry powder inhaler is effective and generally well tolerated in patients with COPD. Although not associated with a statistically significant reduction in mortality versus placebo in the TORCH study (p = 0.052), salmeterol/fluticasone propionate reduced the rate of decline in lung function over the 3 years of the trial and was associated with lower exacerbation rates than the component monotherapies or placebo; other trials revealed clinically significant improvements in health status and dyspnoea scores with salmeterol/fluticasone propionate. Results of the INSPIRE trial suggest that salmeterol/fluticasone propionate is associated with a significantly lower mortality rate than tiotropium bromide monotherapy in patients with COPD; the two treatments had similar effects in terms of exacerbation rates and lung function. Thus, salmeterol/fluticasone propionate is an important option in the treatment of patients with COPD who are appropriate candidates for combination therapy with a long-acting bronchodilator and an inhaled corticosteroid.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Indications for the use of long-acting beta-agonists (LABAs) and inhaled corticosteroids (ICS) in patients with COPD are described in the various international guidelines, but no special recommendations are made concerning the use of combination inhalers containing a LABA as well as an ICS. To determine the place of combination inhalers in the treatment of COPD we reviewed recent literature concerning this subject. On molecular level ICS/LABA combination therapy has anti-inflammatory properties which cannot be attributed to ICS alone. All clinical studies indicate that the two available combinations (salmeterol/fluticasone and formoterol/budesonide) significantly reduce exacerbation rate of moderate/severe exacerbations when compared with placebo. Some studies also showed a significant reduction in exacerbation rate compared with LABA monotherapy, but not compared with ICS monotherapy. From the patient's perspective, ICS/LABA combination inhalers are the first choice when both need to be prescribed, possibly improving patient compliance for ICS. Currently little evidence is available to predict if flexible treatment with LABA/ICS combination inhalers will improve disease control in COPD. Further studies are needed to elucidate the clinical benefit of combination inhalers versus the individual components in different inhalers, and to investigate the clinical benefit of flexible dosing of combination inhalers in patients with COPD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Bronchoconstrictor Agents; Budesonide; Drug Administration Schedule; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Patient Compliance; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor agonists is increasingly used as maintenance therapy in patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of inhaled corticosteroids is thought to be mediated through suppression of airway inflammation, while long-acting beta2-adrenoceptor agonists are thought to work by inducing bronchodilation. However, there is emerging data to indicate that these two classes of drugs interact positively with each other, leading to added or perhaps synergistic benefits for patients. Corticosteroids enhance the expression of beta2-adrenoceptor, thus providing protection against desensitization and development of tolerance to beta2-adrenoceptor agonists, which may occur with prolonged use of these medications. Long-acting beta2-adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory effects of corticosteroids by accelerating nuclear translocation of the glucocorticoid receptor complex, and enhancing transcription and expression of steroid-inducible genes in pro-inflammatory cells. In clinical trials, corticosteroids in combination with long-acting beta2-adrenoceptor agonists reduce exacerbation rates, and improve lung function and health status of patients with moderate to severe asthma or COPD beyond that achieved by individual component therapy. Their effects on mortality are unknown. There is a large clinical trial currently underway, which will provide mortality data by the year 2006. On balance, clinical evidence supports the use of combination therapy in moderate to severe asthma and COPD.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Androstadienes; Animals; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Gene Expression Regulation; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Receptors, Glucocorticoid

Seretide (fluticasone + salmeterol--Allen & Hanburys) and Symbicort (budesonide + formoterol--AstraZeneca) inhalers have recently been licensed in the UK for the symptomatic treatment of patients with severe chronic obstructive pulmonary disease (COPD) and a history of repeated exacerbations. Advertising for Seretide depicts a man and states that the drug "has improved his ability to breathe and reduced his risk of exacerbations", while promotional claims for Symbicort include benefits in "reducing symptoms" and "improving quality of life". Here we assess the place of these fixed-dose combination inhalers containing a corticosteroid and a long-acting beta 2 agonist in the management of patients with COPD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Treatment Outcome

Chronic-obstructive pulmonary disease (COPD) is a global public health problem and its impact is increasing. Although only smoking cessation has been shown to alter the natural history of the disease, current treatment guidelines recommend the use of inhaled bronchodilators to decrease symptoms, improve lung function and quality of life and to prevent exacerbations. For a subset of patients with more severe disease, inhaled corticosteroids may also have a role in achieving these goals. Fluticasone propionate/salmeterol (Advair) or Seretide), GlaxoSmithKline) is a combination inhaled steroid and long-acting bronchodilator that is delivered by a dry-powder inhaler and was recently approved for use in COPD in the US. Fluticasone propionate/salmeterol is a potent bronchodilator and also appears to have important effects on the frequency of exacerbations and overall quality of life for some patients with COPD. Issues of patient selection as well as the pharmacology, efficacy and safety of the drug are discussed.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive

The salmeterol/fluticasone propionate dry powder inhaler (DPI) [Advair Diskus, Seretide Accuhaler] contains the long-acting beta2-adrenoceptor agonist salmeterol and the inhaled corticosteroid fluticasone propionate. In the US, twice-daily salmeterol/fluticasone propionate 50/250 microg is approved for use in adults with chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis, and in the EU, the twice-daily 50/500 microg dosage is approved for use in patients with severe COPD, repeat exacerbations and significant symptoms despite bronchodilator therapy. In patients with moderate-to-severe COPD, twice-daily inhaled salmeterol/fluticasone propionate 50/250 or 50/500 microg for 24-52 weeks improves predose forced expiratory volume in 1 second (FEV1) significantly more than salmeterol monotherapy, improves postdose or postbronchodilator FEV1 significantly more than fluticasone propionate monotherapy and results in clinically significant improvements in health-related quality of life. Salmeterol/fluticasone propionate 50/500 microg significantly reduced annual COPD exacerbations, especially in severe COPD. Some corticosteroid-related adverse events were increased in recipients of fluticasone propionate with or without salmeterol versus salmeterol monotherapy or placebo; withdrawal from fluticasone propionate, including combination therapy, needs careful management to minimise COPD exacerbations. The DPI combining a corticosteroid and long-acting beta2-agonist provides benefits over monotherapy and may encourage patient compliance in COPD.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Area Under Curve; Bronchodilator Agents; Clinical Trials as Topic; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Half-Life; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life

Seretide (Advair [North America], GlaxoSmithKline) is an inhaler combination formulation intended for the maintenance therapy of obstructive airways disease. Seretide was developed and made available initially as three multi-dose, dry powder inhaler formulations delivering 50 microg/puff of the long acting beta(2) agonist salmeterol and either 100, 250 or 500 microg/puff of the inhaled corticosteroid fluticasone propionate. In addition to the initial multi-dose dry powder inhaler system (Diskus or Accuhaler), a chlorofluorocarbon (CFC)-free pressurised aerosol formulation has become available. Studied mostly extensively as a maintenance therapy for patients with persistent asthma, the combination inhaler is at least equivalent to its components administered separately and is superior to monotherapy with salmeterol or inhaled corticosteroid in both paediatric and adult populations. The combination has a logical role in the treatment of moderate-to-severe asthma, offering the advantage of increased convenience and possibly improved compliance. In addition to improvements in lung function, symptom scores and quality of life, the combination therapy reduces exacerbation rates, an outcome that contributes to favourable cost-effectiveness. A role as initial maintenance therapy in all forms of persistent asthma is also plausible but there are fewer data concerning the impact of Seretide in milder forms of persistent asthma. Clinical trials are underway to examine the potential role of Seretide in patients with chronic obstructive pulmonary disease (COPD). Salmeterol has been shown to be an effective first-line bronchodilator in COPD and fluticasone has been shown to reduce the frequency and or severity of exacerbations in COPD patients in two key trials. At a time when the prevalence of both asthma and COPD is increasing, Seretide is a valuable step in the management of these common obstructive lung diseases.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Inflammatory Agents; Clinical Trials as Topic; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Maintenance and reliever therapy (MART) with inhaled corticosteroid (ICS)/formoterol effectively reduces exacerbations in asthma. We aimed to investigate its efficacy compared with fixed-dose fluticasone/salmeterol in chronic obstructive pulmonary disease (COPD).. Patients with COPD and ≥1 exacerbation in the previous 2 years were randomly assigned to open-label MART (Spiromax budesonide/formoterol 160/4.5 µg 2 inhalations twice daily+1 prn) or fixed-dose therapy (Diskus fluticasone propionate/salmeterol combination (FSC) 500/50 µg 1 inhalation twice daily+salbutamol 100 µg prn) for 1 year. The primary outcome was rate of moderate/severe exacerbations, defined by treatment with oral prednisolone and/or antibiotics.. In total, 195 patients were randomised (MART Bud/Form n=103; fixed-dose FSC n=92). No significant difference was seen between MART and FSC therapy in exacerbation rates (1.32 vs 1.32 /year, respectively, rate ratio 1.05 (95% CI 0.79 to 1.39); p=0.741). No differences in lung function parameters or health status were observed. Total ICS dose was significantly lower with MART than FSC therapy (budesonide-equivalent 928 µg/day vs 1747 µg/day, respectively, p<0.05). Similar proportions of patients reported adverse events (MART Bud/Form: 73% vs fixed-dose FSC: 68%, p=0.408) and pneumonias (MART: 5% vs FSC: 1%, p=0.216).. This first study of MART in COPD found that budesonide/formoterol MART might be similarly effective to fluticasone/salmeterol fixed-dose therapy in moderate to severe patients with COPD, at a lower daily ICS dosage. Further evidence is needed about long-term safety.

Topics: Adrenal Cortex Hormones; Androstadienes; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

In 2019, the U.S. Food and Drug Administration (FDA) approved the first generic maintenance inhaler for asthma and chronic obstructive pulmonary disease (COPD). The inhaler, Wixela Inhub (fluticasone-salmeterol; Viatris), is a substitutable version of the dry powder inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline). When approving complex generic products like inhalers, the FDA applies a special "weight-of-evidence" approach. In this case, manufacturers were required to perform a randomized controlled trial in patients with asthma but not COPD, although the product received approval for both indications.. To compare the effectiveness and safety of generic (Wixela Inhub) and brand-name (Advair Diskus) fluticasone-salmeterol among patients with COPD treated in routine care.. A 1:1 propensity score-matched cohort study.. A large, longitudinal health care database.. Adults older than 40 years with a diagnosis of COPD.. Incidence of first moderate or severe COPD exacerbation (effectiveness outcome) and incidence of first pneumonia hospitalization (safety outcome) in the 365 days after cohort entry.. Among 45 369 patients (27 305 Advair Diskus users and 18 064 Wixela Inhub users), 10 012 matched pairs were identified for the primary analysis. Compared with Advair Diskus use, Wixela Inhub use was associated with a nearly identical incidence of first moderate or severe COPD exacerbation (hazard ratio [HR], 0.97 [95% CI, 0.90 to 1.04]) and first pneumonia hospitalization (HR, 0.99 [CI, 0.86 to 1.15]).. Follow-up times were short, reflecting real-world clinical practice. The possibility of residual confounding cannot be completely excluded.. Use of generic and brand-name fluticasone-salmeterol was associated with similar outcomes among patients with COPD treated in routine practice.. National Heart, Lung, and Blood Institute.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchodilator Agents; Cohort Studies; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Pneumonia; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

COPD is a heterogeneous disease and patients may respond differently to therapies depending on baseline symptom burden.. This post-hoc analysis from the 52-week FLAME study investigated the impact of baseline symptom burden in terms of health status, dyspnoea, bronchitis status, eosinophil levels and smoking status on the subsequent risk of moderate or severe exacerbations. Health status was measured by St. George's Respiratory Questionnaire (SGRQ) score (higher ≥46.6 and lower < 46.6) and COPD Assessment Test (CAT) score (higher ≥17 and lower < 17); dyspnoea and bronchitis were assessed via an electronic diary (eDiary). Differential response to once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg versus twice-daily salmeterol/fluticasone (SFC) 50/500 μg was assessed.. Data from 3354 patients was analysed. The risk of exacerbations was lower in patients who had less severe health impairment (rate ratio [RR] [95% CI]): SGRQ-C, (0.88 [0.78, 0.99]); CAT, 0.85 [0.75, 0.96]) and lower dyspnoea (0.79 [0.69, 0.90]) at baseline versus those with more severe health impairment and higher dyspnoea, respectively. Compared with SFC, IND/GLY led to better prevention of moderate-to-severe exacerbations in the majority of groups studied.. Patients with more severe health status impairment and greater symptom burden at baseline subsequently experienced more exacerbations in the FLAME study. IND/GLY was overall more effective in preventing exacerbations versus SFC, regardless of baseline symptom burden. Our results suggest that future studies on novel exacerbation therapies should consider targeting patients with higher symptom burden at baseline.. NCT01782326.

Topics: Aged; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glycopyrrolate; Health Status; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Surveys and Questionnaires

The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes.. FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations. In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50 μg once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use.. This post-hoc analysis included 2557 men and 805 women. Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ≥2 exacerbations in the previous year. Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73-0.91], 0.89 [0.74-1.07] in men and women, respectively). Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70-0.89] and 0.76 [0.63-0.91] in men and women, respectively). Results were similar for all (mild/moderate/severe) exacerbations. Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women. The smaller sample size for women may account for some observed discrepancies in treatment responses.. Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC. Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis.. Post hoc analysis of the FLAME study. ClinicalTrials.gov number: NCT01782326 . Registered 1 February 2013.

Topics: Aged; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Sex Characteristics; Treatment Outcome

There are no studies on withdrawal of inhaled corticosteroids in patients on long-term triple therapy in the absence of frequent exacerbations.. To evaluate the efficacy and safety of direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in nonfrequently exacerbating patients with chronic obstructive pulmonary disease (COPD).. This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50 μg once daily) or continuation of triple therapy (tiotropium [18 μg] once daily plus combination of salmeterol/fluticasone propionate [50/500 μg] twice daily) in nonfrequently exacerbating patients with moderate-to-severe COPD. Primary endpoint was noninferiority on change from baseline in trough FEV. In patients with COPD without frequent exacerbations on long-term triple therapy, the direct de-escalation to indacaterol/glycopyrronium led to a small decrease in lung function, with no difference in exacerbations. The higher exacerbation risk in patients with ≥300 blood eosinophils/μl suggests that these patients are likely to benefit from triple therapy. Clinical trial registered with www.clinicaltrials.gov (NCT 02603393).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Tiotropium Bromide; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.. CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV. IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID- patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID- patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID- patients.. IND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.. Clinicaltrials.gov NCT01782326 .

Topics: Aged; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones

In this 12-week, multicentre, double-blind study, patients with moderate-to-severe COPD and up to one exacerbation in previous year, receiving SFC for ≥3 months, were randomized to continue SFC 50/500 μg twice daily (bd) or switch to IND/GLY 110/50 μg once daily (od). Primary endpoint was pre-dose trough forced expiratory volume in 1 s (FEV. FLASH demonstrated that a direct switch to IND/GLY from SFC improved pre-dose FEV

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Drug Monitoring; Drug Substitution; Female; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Respiratory Function Tests; Treatment Outcome

In this pooled analysis, we compared the effect of indacaterol/glycopyrronium (IND/GLY) by sex versus other commonly used chronic obstructive pulmonary disease (COPD) treatments and placebo. Male and female patients with moderate-to-very-severe COPD who had participated in six randomized controlled trials were included in the analysis. Baseline demographics and disease characteristics were analyzed by sex, and any differences noted. The effects of IND/GLY versus salmeterol/fluticasone (SFC), glycopyrronium, tiotropium and placebo, on lung function and the patient-reported outcomes (health status, dyspnea, rescue medication use and symptoms) were assessed by sex after 26 weeks treatment. The analysis population comprised 4719 men and 1389 women. Most baseline parameters differed significantly between men and women. Nonetheless, despite these differences in baseline characteristics, IND/GLY significantly improved lung function versus placebo (p < 0.0001) and all active comparators (p < 0.01) in men and women. Overall, IND/GLY showed better improvement in dyspnea and health status compared with all other treatments in both sex. Greater reduction of rescue medication use was observed with IND/GLY versus placebo and other treatments (all p < 0.01 expect IND/GLY versus SFC). Although some variability was observed, improvements in health status, dyspnea, rescue medication use and symptoms were generally larger in women than in men. Irrespective of sex, IND/GLY provided superior efficacy to monotherapy or SFC in both men and women. Small differences in efficacy response by sex were observed, which should be evaluated further in prospective clinical studies. Nevertheless, the benefits observed with IND/GLY confirm dual bronchodilator as the preferred therapy in patients with moderate-to-very-severe COPD regardless of sex.

Topics: Aged; Bronchodilator Agents; Drug Combinations; Dyspnea; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Glycopyrrolate; Health Status; Humans; Indans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Severity of Illness Index; Sex Factors; Tiotropium Bromide; Vital Capacity

This study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year.. A previously published and validated patient-level simulation model was adapted using clinical data from the FLAME trial and real-world cost data from the ARCTIC study. Costs (total monetary costs comprising drug, maintenance, exacerbation, and pneumonia costs) and health outcomes (life-years (LYs), quality-adjusted life-years (QALYs)) were projected over various time horizons (1, 5, 10 years, and lifetime) from the Swedish payer's perspective and were discounted at 3% annually. Uncertainty in model input values was studied through one-way and probabilistic sensitivity analyses. Subgroup analyses were also performed.. IND/GLY was associated with lower costs and better outcomes compared with SFC over all the analysed time horizons. Use of IND/GLY resulted in additional 0.192 LYs and 0.134 QALYs with cost savings of €1211 compared with SFC over lifetime. The net monetary benefit (NMB) was estimated to be €8560 based on a willingness-to-pay threshold of €55,000/QALY. The NMB was higher in the following subgroups: severe (GOLD 3), high risk and more symptoms (GOLD D), females, and current smokers.. IND/GLY is a cost-effective treatment compared with SFC in COPD patients with mMRC dyspnea grade ≥ 2, moderate to very severe airflow limitation, and ≥1 exacerbation in the preceding year.

Topics: Aged; Cost-Benefit Analysis; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Models, Economic; Population Surveillance; Pulmonary Disease, Chronic Obstructive; Quinolones; Sweden

Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo. During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.In patients using ICS during GL1 and using ICS 0-50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Bronchi; Bronchodilator Agents; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Forced Expiratory Volume; Humans; Inflammation; Linear Models; Male; Middle Aged; Netherlands; Neutrophils; Pulmonary Disease, Chronic Obstructive; Sputum; Withholding Treatment

Combinations of drugs with distinct and complementary mechanisms of action may offer improved efficacy in the treatment of chronic obstructive pulmonary disease (COPD). In two 12-week, double-blind, parallel-group studies, patients with COPD were randomized 1:1:1 to once-daily umeclidinium (UMEC; 62.5 μg and 125 μg) or placebo (PBO), added to twice-daily fluticasone propionate/salmeterol (FP/SAL; 250/50 μg). In both studies, the primary efficacy measure was trough forced expiratory volume in 1 second (FEV1) at Day 85. Secondary endpoints were weighted-mean (WM) FEV1 over 0-6 hours post-dose (Day 84) and rescue albuterol use. Health-related quality of life outcomes (St. George's Respiratory Questionnaire [SGRQ] and COPD assessment test [CAT]) were also examined. Safety was assessed throughout. Both UMEC+FP/SAL doses provided statistically significant improvements in trough FEV1 (Day 85: 0.127-0.148 L) versus PBO+FP/SAL. Similarly, both UMEC+FP/SAL doses provided statistically-significant improvements in 0-6 hours post-dose WM FEV1 versus PBO+FP/SAL (Day 84: 0.144-0.165 L). Rescue use over Weeks 1-12 decreased with UMEC+FP/SAL in both studies versus PBO+FP/SAL (Study 1, 0.3 puffs/day [both doses]; Study 2, 0.5 puffs/day [UMEC 125+FP/SAL]). Decreases from baseline in CAT score were generally larger for both doses of UMEC+FP/SAL versus PBO+FP/SAL (except for Day 84 Study 2). In Study 1, no differences in SGRQ score were observed between UMEC+FP/SAL and PBO+FP/SAL; however, in Study 2, statistically significant improvements were observed with UMEC 62.5+FP/SAL (Day 28) and UMEC 125+FP/SAL (Days 28 and 84) versus PBO+FP/SAL. The incidence of on-treatment adverse events across all treatment groups was 37-41% in Study 1 and 36-38% in Study 2. Overall, these data indicate that the combination of UMEC+FP/SAL can provide additional benefits over FP/SAL alone in patients with COPD.

Topics: Administration, Inhalation; Aged; Albuterol; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Treatment Outcome; Vital Capacity

We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.. Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57-75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.. For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.. Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Delayed-Action Preparations; Double-Blind Method; Eosinophils; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Most guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.. We conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.. A total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).. Indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.).

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones

Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE(2)SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein.. In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate-severe exacerbations within 12 months, and were receiving ICS/LABA FDC for ≥3 months. The primary efficacy measure is the rate of moderate or severe COPD exacerbations per participant per year. The secondary efficacy outcomes include mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) over 52 weeks, rate of severe exacerbations, and rate of moderate, severe, or antibiotic-treated exacerbations. Additional assessments include spirometry, rescue medication use, the COPD assessment test, daily symptoms using the EXACT-Respiratory symptoms (E-RS) questionnaire, all-cause and COPD-related hospitalizations, and safety and pharmacokinetic measures.. Across 17 countries, 2,354 participants were randomized from September 2011 to October 2014. Enrollment goal was met in October 2014, and study completion occurred in June 2016.. This study will further characterize the effects of roflumilast added to ICS/LABA on exacerbation rates, lung function, and health of severe-very severe COPD participants at risk of further exacerbations. The results will determine the clinical benefits of roflumilast combined with standard-of-care inhaled COPD treatment.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Aminopyridines; Benzamides; Bronchitis, Chronic; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Cyclopropanes; Disease Progression; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Phosphodiesterase 4 Inhibitors; Pulmonary Disease, Chronic Obstructive; Research Design; Severity of Illness Index; Spirometry; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vital Capacity

Current guidelines recommend combining long-acting bronchodilators with different modes of action in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). We evaluated the effects of airway dimensions and pulmonary function with tiotropium plus indacaterol versus Advair(®).. Subjects (n = 46) were randomized to receive tiotropium (18 μg once daily) plus indacaterol (150 μg once daily) or Advair(®) (50/250 μg twice daily) for 16 weeks. Airway geometry was determined by quantitative computed tomography (luminal area, Ai; total area of the airway, Ao; wall area, WA; and percentage wall area, WA/Ao and wall thickness, T). Spirometry (forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC and inspiratory capacity, IC) and St. George's Respiratory Questionnaire (SGRQ) were evaluated.. Tiotropium plus indacaterol significantly increased CT-indices including Ai corrected for body surface area (Ai/BSA), and decreased WA/BSA, WA/Ao and T/√BSA compared with Advair(®) (p < 0.05, respectively). In physiological parameters, mean difference in IC was significantly higher under treatment with tiotropium plus indacaterol than Advair(®) (p < 0.05). The changes in Ai/BSA, WA/BSA, WA/Ao and T/√BSA were significantly correlated with changes in IC (r = 0.535, p = 0.011; r = -0.688, p < 0.001; r = -0.555, p = 0.002 and r = -0.542, p = 0.007; respectively). There were more significant improvements in SGRQ scores after treatment with tiotropium plus indacaterol than Advair(®).. These findings suggest that dual bronchodilation with tiotropium plus indacaterol is superior in airway geometry and lung function compared with Advair(®) in COPD.

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Scopolamine Derivatives; Spirometry; Surveys and Questionnaires; Tiotropium Bromide

We previously observed that 30 months of inhaled corticosteroid (ICS) treatment can attenuate FEV1 decline in COPD, but it is unclear whether withdrawal induces a relapse. We hypothesized that FEV1 decline, airway hyperresponsiveness (AHR), and quality of life (QOL) deteriorate after ICS cessation even after prolonged use.. One hundred fourteen patients with moderate to severe COPD finished randomized 6-month or 30-month treatment with fluticasone (500 μg bid), 30-month treatment with fluticasone and salmeterol (500/50 μg bid), or placebo (first part of the Groningen and Leiden Universities Corticosteroids in Obstructive Lung Disease [GLUCOLD] study [GL1]). The subsequent 5 years, patients were prospectively followed annually, treated by their physician (GLUCOLD follow-up study [GL2]). Postbronchodilator FEV1, AHR, and QOL were initially recorded at baseline, at 30 months (GL1), and annually during GL2. Analysis was performed by linear mixed-effects models.. Among 101 adherent patients during GL1, 79 patients started and 58 completed GL2. Patients using ICSs during GL1, but only using ICSs 0% to 50% of the time during GL2 (n = 56 of 79), had significantly accelerated annual FEV1 decline compared with GL1 (difference GL2-GL1 [95% CI]: 30-month treatment with fluticasone and salmeterol, -68 mL/y [-112 to -25], P = .002; 30-month treatment with fluticasone, -73 mL/y [-119 to -26], P = .002), accompanied by deterioration in AHR and QOL.. ICS discontinuation after 30 months in COPD can worsen lung function decline, AHR, and QOL during 5-year follow-up. This suggests that ICS treatment lacks sustained disease-modifying effect after treatment cessation.. ClinicalTrials.gov; No.: NCT00158847; URL: www.clinicaltrials.gov.

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Cohort Studies; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quality of Life; Recurrence; Withholding Treatment

Inhaled corticosteroid/long-acting β2-agonist combinations (ICS/LABA) have emerged as first line therapies for chronic obstructive pulmonary disease (COPD) patients with exacerbation history. No randomized clinical trial has compared exacerbation rates among COPD patients receiving budesonide/formoterol combination (BFC) and fluticasone/salmeterol combination (FSC) to date, and only limited comparative data are available. This study compared the real-world effectiveness of approved BFC and FSC treatments among matched cohorts of COPD patients in a large US managed care setting.. COPD patients (≥40 years) naive to ICS/LABA who initiated BFC or FSC treatments between 03/01/2009-03/31/2012 were identified in a geographically diverse US managed care database and followed for 12 months; index date was defined as first prescription fill date. Patients with a cancer diagnosis or chronic (≥180 days) oral corticosteroid (OCS) use within 12 months prior to index were excluded. Patients were matched 1-to-1 on demographic and pre-initiation clinical characteristics using propensity scores from a random forest model. The primary efficacy outcome was COPD exacerbation rate, and secondary efficacy outcomes included exacerbation rates by event type and healthcare resource utilization. Pneumonia objectives included rates of any diagnosis of pneumonia and pneumonia-related healthcare resource utilization.. Matching of the identified 3,788 BFC and 6,439 FSC patients resulted in 3,697 patients in each group. Matched patients were well balanced on age (mean=64 years), gender (BFC: 52% female; FSC: 54%), prior COPD-related medication use, healthcare utilization, and comorbid conditions. During follow-up, no significant difference was seen between BFC and FSC patients for number of COPD-related exacerbations overall (rate ratio [RR]=1.02, 95% CI=[0.96,1.09], p=0.56) or by event type: COPD-related hospitalizations (RR=0.96), COPD-related ED visits (RR=1.11), and COPD-related office/outpatient visits with OCS and/or antibiotic use (RR=1.01). The proportion of patients diagnosed with pneumonia during the post-index period was similar for patients in each group (BFC =17.3%, FSC =19.0%, odds ratio=0.92 [0.81,1.04], p=0.19), and no difference was detected for pneumonia-related healthcare utilization by place of service.. This study demonstrated no difference in COPD-related exacerbations or pneumonia events between BFC and FSC treatment groups for patients new to ICS/LABA treatment in a real-world setting.. ClinicalTrials.gov identifier NCT01921127 .

Topics: Administration, Inhalation; Administrative Claims, Healthcare; Aged; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Cohort Studies; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; United States

Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD).. Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured.. Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo). However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant.. This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population. In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo. Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Asian People; Biomarkers; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Health Status; Humans; Inflammation Mediators; Japan; Leukocyte Count; Lung; Male; Middle Aged; Neutrophils; Pulmonary Disease, Chronic Obstructive; Sputum; Surveys and Questionnaires; Time Factors; Treatment Outcome

Umeclidinium (UMEC; long-acting muscarinic antagonist [LAMA])/vilanterol (VI; long-acting beta2-agonist [LABA]) and fluticasone propionate/salmeterol (FP/SAL) (inhaled corticosteroid/LABA) are approved maintenance therapies for chronic obstructive pulmonary disease (COPD). Two studies compared efficacy and safety of UMEC/VI with FP/SAL in patients with moderate-to-severe COPD with no exacerbations in the previous year.. In these 12-week, multicenter, double-blind, parallel-group, double-dummy trials, randomized (1:1) patients received once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 250/50 mcg (DB2114930 n = 353 and 353; DB2114951 n = 349 and 348, respectively; intent-to-treat). Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, dyspnea, quality of life (QoL) and safety.. UMEC/VI demonstrated statistically significant, clinically meaningful improvements in lung function measures versus FP/SAL. For 0-24 h wmFEV1 (Day 84), improvements with UMEC/VI versus FP/SAL were 74 mL (95% confidence interval [CI]: 38-110; DB2114930) and 101 mL (63-139; DB2114951) (both p < 0.001). Trough FEV1 improvements were 82 mL (45-119) and 98 mL (59-137) (both p < 0.001) for UMEC/VI versus FP/SAL, respectively. Both treatments demonstrated similar, clinically meaningful improvements from baseline in dyspnea (Transition Dyspnea Index focal score >1 unit) and QoL (St George's Respiratory Questionnaire Total score >4-unit decrease) in both studies with no statistical differences between treatments. Adverse event rates were similar: 26 and 30% UMEC/VI; 27 and 31% FP/SAL.. Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in statistically significant, clinically meaningful improvements in lung function versus twice-daily FP/SAL 250/50 mcg in patients with moderate-to-severe COPD with infrequent exacerbations. Both treatments improved dyspnea and QoL.. DB2114930/NCT01817764; DB2114951/NCT01879410.

Topics: Administration, Inhalation; Aged; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quality of Life; Recurrence; Severity of Illness Index; Treatment Outcome

The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.. In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.. Overall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).. These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Glycopyrrolate; Humans; Indans; Lung; Male; Middle Aged; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quinolones; Recovery of Function; Severity of Illness Index; Spirometry; Surveys and Questionnaires; Time Factors; Treatment Outcome

Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD). This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.. Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg. Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.. Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001). UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL. Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George's Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks. The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.. Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.. NCT01822899 Registration date: March 28, 2013.

Topics: Administration, Inhalation; Adult; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Treatment Outcome

Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is important because patients with ACOS have significantly worse outcomes compared with those with asthma or chronic obstructive pulmonary disease (COPD) alone. Inhaled corticosteroids (ICS), together with a long-acting β2 agonist (LABA), are recommended, but no therapeutic studies for ACOS have been conducted. Recently, fluticasone furoate/vilanterole (FF/VI) has been approved as the first once-daily ICS/LABA combination therapy for asthma and COPD.. A 12-week, randomized, open-label cross-over study was conducted in 16 patients with ACOS to compare the effectiveness of once-daily FF/VI 200/25 μg vs. twice-daily fluticasone propionate/salmeterol (FP/SAL) 500/50 μg. The study period included a 4-week run-in, the first 4-week treatment, and the second 4-week treatment. Respiratory functions, including forced expiratory volume in 1 s (FEV1) and respiratory impedance using the forced oscillation technique (FOT), were measured, as was fractional exhaled nitric oxide (FeNO). A COPD assessment test (CAT) scores and asthma control test (ACT) scores were recorded 0, 4, and 8 weeks after randomization.. The mean values for the FEV1 were 1.33 (±0.29) L in the run-in period, 1.38 (±0.39) L after the FP/SAL treatment period, and 1.47 (±0.38) L after the FF/VI treatment period. The FEV1 value after the FF/VI treatment was significantly greater than the value after the run-in period (p < 0.01). FOT parameters, FeNO levels, CAT scores, ACT scores, and other blood tests were not significantly different during the run-in period, the FP/SAL treatment period, and the FF/VI treatment period.. FF/VI, the first once-daily ICS/LABA, can provide substantial improvement in lung functions, indicating that FF/VI should be considered for the regular treatment of ACOS.

Topics: Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Benzyl Alcohols; Chlorobenzenes; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

Triple therapy using salmeterol/fluticasone propionate (FP) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease (COPD), but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients. The effects of of salmeterol/fluticasone propionate 50/250 μg (SFC250) twice daily plus tiotropium 18 μg (TIO) once daily and individual treatments on lung function were compared.. Fifty three Japanese COPD patients participated in this randomized, double-blind, double-dummy, Williams square design crossover study. Lung function was assessed by plethysmography and spirometry.. The primary endpoint of postdose specific airway conductance area under the curve (AUC0-4h) on day 28 was significantly higher following SFC250 + TIO (0.854) compared with TIO (0.737, 15.8%) and SFC250 (0.663, 28.8%) alone. SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO (0.161 L, P<0.001) and SFC250 (0.103 L, P=0.008). SFC250 + TIO significantly improved residual volume compared with TIO (P<0.001) and SFC250 (P=0.003) on day 28. Nonsignificant improvements were seen in trough inspiratory capacity, total lung capacity, and thoracic gas volume. There was no mean change seen in rescue medication.. Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD. There was improvement in few symptoms, but no mean change was seen in patient-reported outcomes measured by rescue medication use.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Area Under Curve; Bronchodilator Agents; Cholinergic Antagonists; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Japan; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Plethysmography; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Recovery of Function; ROC Curve; Severity of Illness Index; Spirometry; Time Factors; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Macrophages constitute a heterogeneous cell population with pro- (MΦ1) and anti-inflammatory (MΦ2) cells. The soluble chitinase-like-protein YKL-40 is expressed in macrophages and various other cell types, and has been linked to a variety of inflammatory diseases, including COPD. Dexamethasone strongly reduces YKL-40 expression in peripheral blood mononuclear cells (PBMC) in vitro. We hypothesized that: a) YKL-40 is differentially expressed by MΦ1 and MΦ2, b) is decreased by corticosteroids and c) that long-term treatment with inhaled corticosteroids (ICS) affects YKL-40 levels in serum and sputum of COPD patients.. Monocytes of healthy subjects were cultured in vitro for 7 days with either GM-CSF or M-CSF (for MΦ1 and MΦ2, respectively) and stimulated for 24 h with LPS, TNFα, or oncostatin M (OSM). MΦ1 and MΦ2 differentiation was assessed by measuring secretion of IL-12p40 and IL-10, respectively. YKL-40 expression in macrophages was measured by quantitative RT-PCR (qPCR) and ELISA; serum and sputum YKL-40 levels were analyzed by ELISA.. Pro-inflammatory MΦ1 cells secreted significantly more YKL-40 than MΦ2, which was independent of stimulation with LPS, TNFα or OSM (p < 0.001) and confirmed by qPCR. Dexamethasone dose-dependently and significantly inhibited YKL-40 protein and mRNA levels in MΦ1. Serum YKL-40 levels of COPD patients were significantly higher than sputum YKL-40 levels but were not significantly changed by ICS treatment.. YKL-40 secretion from MΦ1 cells is higher than from MΦ2 cells and is unaffected by further stimulation with pro-inflammatory agents. Furthermore, YKL-40 release from cultured monocyte-derived macrophages is inhibited by dexamethasone especially in MΦ1, but ICS treatment did not change YKL-40 serum and sputum levels in COPD. These results indicate that YKL-40 expression could be used as a marker for MΦ1 macrophages in vitro, but not for monitoring the effect of ICS in COPD.. ClinicalTrials.gov, registration number: NCT00158847.

Topics: Adipokines; Administration, Inhalation; Aged; Anti-Inflammatory Agents; Biomarkers; Bronchodilator Agents; Cells, Cultured; Chitinase-3-Like Protein 1; Dexamethasone; Dose-Response Relationship, Drug; Down-Regulation; Drug Administration Schedule; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Inflammation Mediators; Lectins; Macrophages; Male; Middle Aged; Netherlands; Phenotype; Pulmonary Disease, Chronic Obstructive; Sputum; Time Factors; Treatment Outcome

The object of this study was to assess whether a capsule-based and multidose dry powder inhaler containing salmeterol (as xinafoate salt) 50 μg plus fluticasone propionate (FP) 250 μg [combination (SFC 50/250)] could be equivalent in terms of in vivo drug delivery and systemic exposure.. This was a randomized, double-blind, double-dummy, replicate treatment design comparative bioavailability study of SFC 50/250 delivered in a capsule-based inhaler (Rotahaler®) and a multidose dry powder inhaler (Diskus®). Subjects with asthma or chronic obstructive pulmonary (COPD) disease (n=60) were randomized to receive twice-daily SFC 50/250 via a Rotahaler and via Diskus each for two 10-day treatment periods (GlaxoSmithKline Protocol ASR114334).. For FP and salmeterol, the in vitro aerodynamic particle size profiles were within±15% of Diskus for the fine particle mass (FPM) and emitted dose (ED) using the Andersen Cascade Impactor, and ED, mass median aerodynamic diameter, and geometric standard deviation using the New Generation Impactor (NGI). This was also the case for FP but not salmeterol for FPM and fine particle dose using the NGI. For the combined asthma and COPD subjects, the plasma AUC and Cmax for FP and salmeterol were higher for Rotahaler:Rotahaler/Diskus geometric mean ratios (90% confidence intervals) for FP AUC0-τ of 1.52 (1.37-1.67) and Cmax of 1.94 (1.75-2.10) and salmeterol AUC0-τ of 1.15 (1.09-1.21) and Cmax of 1.56 (1.42-1.67). Corresponding values for the primary pharmacodynamic endpoint, weighted mean (0-12 hr) serum cortisol, were 0.928 (0.886-0.971). Inhaled FP/salmeterol via both inhalers was well-tolerated. One serious adverse event, considered possibly related to study medication, resulted in subject withdrawal from the study.. The in vitro tests and systemic pharmacodynamic endpoints revealed no major differences between the two inhalers, but lacked predictive power and sensitivity to guide in vivo drug delivery performance and systemic exposure. Based on pharmacokinetic endpoints, the inhalers were not considered bioequivalent in terms of systemic exposure. Further studies to refine the Rotahaler performance are ongoing.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aerosols; Aged; Albuterol; Androstadienes; Area Under Curve; Asthma; Biological Availability; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Dry Powder Inhalers; Equipment Design; Female; Fluticasone-Salmeterol Drug Combination; Humans; Lung; Male; Middle Aged; New South Wales; New Zealand; Particle Size; Powders; Pulmonary Disease, Chronic Obstructive; Treatment Outcome; Young Adult

Fluticasone furoate/vilanterol trifenatate (FF/VI) is a once-daily inhaled corticosteroid/long-acting β₂-agonist combination in development for chronic obstructive pulmonary disease (COPD) treatment. We compared the efficacy and safety of FF/VI versus fluticasone propionate/salmeterol (FP/SAL) twice daily over 12 weeks. Moderate to very severe COPD patients received FF/VI 100/25 μg once daily in the morning (n=266) or FP/SAL 500/50 μg twice daily (n=262). The primary end-point was a change from baseline in 0-24 h weighted mean forced expiratory volume in 1 s (wmFEV₁) at 12 weeks. Additional end-points included time to 100 mL improvement from baseline on day 1 and a change from baseline in St George's Respiratory Questionnaire (SGRQ). Safety was also assessed. wmFEV₁ (mean 130 mL) was greater and time to 100 mL improvement shorter (median 16 min) with FF/VI than FP/SAL (weighted mean 108 mL, median 28 min). Health status (SGRQ total score) improved in both groups (FF/VI -4.3 units, FP/SAL -3.0 units). Differences between treatments were not statistically significant. Six patients in the FF/VI (2%) and three in the FP/SAL (1%) arm experienced serious adverse events, none of which were considered to be drug related. Improvements in lung function and health status were not significantly different between FF/VI 100/25 μg once daily and FP/SAL 500/50 μg twice daily; there was no apparent difference between the safety profiles of either therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Severity of Illness Index; Smoking; Surveys and Questionnaires; Treatment Outcome

The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients.. The trial was a 12-week multicentre, randomised, double-blind, double dummy study; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 μg or FP/S 500/50 μg twice daily. The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre-dose in the first 30 minutes in forced expiratory volume in the first second (FEV1). Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St. George's Respiratory Questionnaire, six minute walking test and COPD exacerbations.. BDP/FF was equivalent to FP/S in terms of TDI score and superior in terms of FEV1 change from pre-dose (p < 0.001). There were no significant differences between treatments in secondary outcome measures, confirming overall comparability in terms of efficacy and tolerability. Moreover, a clinically relevant improvement (>4 units) in SGRQ was detected in the BDP/FF group only.. BDP/FF extrafine combination provides COPD patients with an equivalent improvement of dyspnoea and a faster bronchodilation in comparison to FP/S.. ClinicalTrials.gov: NCT01245569.

Topics: Albuterol; Androstadienes; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

The interleukin (IL)-32/tumor necrosis factor (TNF) a pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease (COPD) inflammation. Inhaled corticosteroids (ICS) in combination with long-acting β2-agonists (LABA) have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain.. Patients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate (SF; Seretide, GlaxoSmithKline) Diskus (50/500 µg twice daily) or ipratropium bromide/salbutamol (IS; Combivent, Boehringer Ingelheim) MDI (42 µg/240 µg quartic daily) for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-α, the number of neutrophils and eosinophils were measured.. Following 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-α in sputum (P = 0.004) was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance (P = 0.028) but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George's respiratory questionnaire in both the SF (P = 0.004) and IS (P = 0.030) treatment groups, but no evidence of improvement in lung function was observed in either group.. The sputum TNF-α and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.

Topics: Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Inflammatory Agents; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Interleukins; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

Chronic obstructive pulmonary disease (COPD) affects millions worldwide. Although many therapies exist and are being developed to relieve symptoms and reduce mortality, few data are available to understand which of the therapeutic alternatives is the most cost-effective for COPD patients in everyday clinical practice, especially for traditional Chinese medicine (TCM). Comparative effectiveness research can help patients, clinicians, and decision-makers make best informed treatment decisions where such evidence was previously lacking. This study aims to compare the effectiveness and economic evaluation of three treatments: (1) conventional Western medicine; (2) TCM treatments, which have been evaluated and have certain effect; and (3) a combination of both conventional Western medicine and TCM treatments, and then determine which treatment is the most suitable for COPD patients.. A multicenter, pragmatic, randomized, controlled trial is adopted. A total of 360 patients will be recruited and randomly assigned to one of the three treatments group, with 120 in each group. Patients in the conventional Western medicine group will be given Salbutamol, Formoterol, Salmeterol/fluticasone, respectively, according to the guidelines. For the TCM group, patients will be given Bufei granule, Bu-Fei Jian-Pi granule, Bu-Fei Yi-Shen granule, and Yi-Qi Zi-Shen granule based on their corresponding TCM syndrome patterns, respectively. For the combination of conventional medicine and TCM treatments group, patients will be given a combination of conventional Western medicine and TCM granules. Treatments in each group are recognized as a whole comprehensive intervention. After the 26-week treatment, another 26 weeks will be followed up. The outcome measures including the frequency and duration of acute exacerbations, lung function, dyspnea, exercise capacity, quality of life, and economic evaluation will be assessed.. It is hypothesized that each of the three treatments will have beneficial effects in reducing the frequency and duration of acute exacerbations, improving exercise capacity and psychosocial function of COPD patients. In addition, the combination of conventional medicine and TCM treatments may be most suitable for COPD patients with better effectiveness and economic evaluation.. ClinicalTrials.gov NCT01836016.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Bronchodilator Agents; China; Comparative Effectiveness Research; Cost-Benefit Analysis; Disease Progression; Drug Combinations; Drug Costs; Drug Therapy, Combination; Drugs, Chinese Herbal; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Lung; Male; Medicine, Chinese Traditional; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Research Design; Time Factors; Treatment Outcome; Young Adult

Fluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL).. Three 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged ≥40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0-24 h weighted mean FEV(1) (wmFEV(1)) on Day 84. Safety was also assessed.. In Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0-24 h wmFEV(1) was significantly greater with FF/VI than FP/SAL (Δ80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0-24 h wmFEV(1) was not significantly greater with FF/VI than FP/SAL (Δ29 mL, P = 0.267; Δ25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (Δ41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments.. Our data suggest that once-daily FF/VI 100/25 mcg provides FEV(1) improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar.. clinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Benzyl Alcohols; Chlorobenzenes; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Treatment Outcome; Vital Capacity

Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD. However, the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known. This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol (FP/SAL) or SAL alone.. Patients (n = 639) aged ≥40 years were randomized to either twice-daily inhaled FP/SAL 250/50 μg or SAL 50 μg. Primary, and secondary, endpoints were rates of recurrent severe, and moderate/severe, exacerbations of COPD. Lung function, health outcomes and levels of biomarkers of systemic inflammation were also assessed.. There was no statistically significant treatment difference in rates of recurrent severe exacerbations (treatment ratio 0.92 [95% CI: 0.58, 1.45]) and moderate/severe exacerbations (0.82 [0.64, 1.06]) between FP/SAL and SAL in the intent-to-treat population. Pre-dose morning FEV1 change from baseline was greater (0.10 L [0.04, 0.16]) with FP/SAL than SAL. No treatment difference was seen for other endpoints including patient-reported health outcomes and biomarker levels for the full cohort.. No significant treatment difference between FP/SAL and SAL was seen in COPD exacerbation recurrence for the complete cohort. Treatment benefit with FP/SAL over SAL (treatment ratio 0.68 [0.47, 0.97]) was seen in patients having FEV1 ≥ 30% and prior exposure to ICS. No unexpected safety issues were identified with either treatment. Patients with the most severe COPD may be more refractory to treatment.. ClinicalTrials.gov (identifier NCT01110200). This study was funded by GlaxoSmithKline (study number ADC113874).

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen). This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 μg once daily or SFC 50/500 μg twice daily. Patients had been receiving SFC 50/500 μg for ≥3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV₁) after 12 weeks (non-inferiority margin of 0.06 L). The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45-26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George's Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected. This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 μg with no efficacy loss.

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Drug Substitution; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Severity of Illness Index; Treatment Outcome; Vital Capacity

The purpose of this exploratory physiological study was to evaluate the effects of inhaled fluticasone/salmeterol combination (FSC) on sensory and physiological responses to exercise in subjects with mild-to-moderate COPD. In a randomized, double-blind, placebo-controlled, crossover study, subjects underwent 6-week treatments with FSC or placebo (PLA). Detailed pulmonary function and constant-work rate cycle exercise tests were performed following each treatment period. Fifteen subjects completed the study (mean ± SD): age 64 ± 10 years; smoking history 47 ± 29 pack-years; post-bronchodilator forced expiratory volume in 1 s 86 ± 15 %predicted (10 mild and 5 moderate COPD); peak incremental oxygen uptake 71 ± 16 %predicted. Compared with PLA, FSC treatment was associated with improved: FEV1 by 0.23 ± 0.18 L; inspiratory capacity by 0.18 ± 0.23 L; functional residual capacity by -0.28 ± 0.30 L; and specific airways resistance by -4.6 ± 4.5 cmH2O s (all p < 0.01). There were no significant changes in dyspnea intensity throughout exercise and endurance time did not change significantly (1.2 ± 3.0 min, p = 0.149). Following FSC, inspiratory capacity at rest and throughout exercise increased by 0.2-0.3 L with concomitant increases in tidal volume and ventilation (p < 0.05). Compared with PLA, the work of breathing and the ratio of respiratory muscle effort to tidal volume improved with FSC during exercise (p < 0.05). In mild-to-moderate COPD, FSC was associated with significant improvements in airway function at rest and during exercise. Despite important mechanical improvements, there were no significant effects on dyspnea intensity and exercise endurance.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Cross-Over Studies; Double-Blind Method; Drug Combinations; Dyspnea; Exercise; Exercise Test; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Oxygen Consumption; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Respiratory Mechanics; Treatment Outcome

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Exercise Tolerance; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Physical Endurance; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Sympathomimetics; Tiotropium Bromide; Treatment Outcome; Walking

The Global initiative for chronic Obstructive Lung Disease (GOLD) Committee has proposed a chronic obstructive pulmonary disease (COPD) assessment framework focused on symptoms and on exacerbation risk. This study will evaluate a symptom and exacerbation risk-based treatment strategy based on GOLD in a real-world setting in Japan. Optimal management of COPD will be determined by assessing symptoms using the COPD Assessment Test (CAT) and by assessing the frequency of exacerbations.. This study (ClinicalTrials.gov identifier: NCT01762800) is a 24-week, multicenter, randomized, double-blind, double-dummy, parallel-group study. It aims to recruit 400 patients with moderate-to-severe COPD. Patients will be randomized to receive treatment with either salmeterol/fluticasone propionate (SFC) 50/250 μg twice daily or with tiotropium bromide 18 μg once daily. Optimal management of patients will be assessed at four-weekly intervals and, if patients remain symptomatic, as measured using the CAT, or experience an exacerbation, they have the option to step up to treatment with both drugs, ie, SFC twice daily and tiotropium once daily (TRIPLE therapy). The primary endpoint of the study will be the proportion of patients who are able to remain on the randomized therapy.. No data are available. This paper summarizes the methodology of the study in advance of the study starting.. The results of this study will help physicians to understand whether TRIPLE therapy is more effective than either treatment strategy alone in controlling symptoms and exacerbations in patients with moderate-to-severe COPD. It will also help physicians to understand the GOLD recommendation work in Japan.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Bronchodilator Agents; Cholinergic Antagonists; Disease Progression; Double-Blind Method; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Japan; Kaplan-Meier Estimate; Lung; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Research Design; Scopolamine Derivatives; Severity of Illness Index; Time Factors; Tiotropium Bromide; Treatment Outcome; Vital Capacity

QVA149 is an inhaled fixed-dose combination therapy under development for the treatment of chronic obstructive pulmonary disease (COPD). It combines indacaterol (a longacting β2-agonist) with glycopyrronium (a longacting muscarinic antagonist) as a dual bronchodilator. We aimed to compare the efficacy, safety, and tolerability of QVA149 versus salmeterol-fluticasone (SFC) over 26 weeks in patients with moderate-to-severe COPD.. In this multicentre double-blind, double-dummy, parallel-group study, 523 patients (age 40 years or older, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages II-III, without exacerbations in the previous year) were randomly assigned (1:1; via automated, interactive response technology and stratified for smoking status) to once-daily QVA149 110/50 μg or twice-daily SFC 50/500 μg for 26 weeks. Efficacy was assessed in the full analysis set (randomised patients who received at least one dose of study drug); safety was assessed in all patients who received at least one dose of study drug. The primary endpoint was to demonstrate the superiority of QVA149 compared with SFC for the standardised area under the curve from 0 to 12 h post dose for forced expiratory volume in 1 second (FEV1 AUC0-12h) after 26 weeks of treatment. This trial was registered at ClinicalTrial.gov, NCT01315249.. Between March 25, 2011, and March 12, 2012, 259 patients were randomly assigned to receive QVA149 and 264 to receive SFC. At week 26, FEV1 AUC0-12h was significantly higher with QVA149 than with SFC (treatment difference 0·138 L; 95% CI 0·100-0·176; p<0·0001). Overall incidence of adverse events (including COPD exacerbations) was 55·4% (143 of 258) for the QVA149 group and 60·2% (159 of 264) for the SFC group. Incidence of serious adverse events was similar between treatment groups (QVA149, 13 of 258 [5·0%]; SFC 14 of 264 [5·3%]); COPD worsening was the most frequent serious adverse event (one of 13 [0·4%] and three of 14 [1·1%], respectively).. Once-daily QVA149 provides significant, sustained, and clinically meaningful improvements in lung function versus twice-daily SFC, with significant symptomatic benefit. These results indicate the potential of dual bronchodilation as a treatment option for non-exacerbating symptomatic COPD patients.. Novartis Pharma AG.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Sympathomimetics; Treatment Outcome

Patients with severe or very severe chronic obstructive pulmonary disease (COPD) frequently suffer repeated exacerbations generating high health care utilization costs. Combined corticosteroid and bronchodilator treatment using a single inhaler might - via improved compliance - reduce exacerbation rates.. Our aim was to obtain descriptive data on exacerbation rates in patients with severe or very severe COPD (GOLD Stages III and IV as per GOLD 2009 classification) receiving salmeterol xinafoate/fluticasone propionate via a single inhaler (SFC) or via separate inhalers (Sal/FP) in addition to individual existing therapy in order to investigate the potential benefit of a fixed combination device as compared with two separate devices due to potentially improved patients' compliance.. This prospective, randomized, open-label, parallel-group, multi-center, exploratory study was conducted in Germany in 2007-2009. Patients were required to have suffered ≥ 2 moderate/severe exacerbations in the preceding year.. 213 patients (SFC: 108 patients, Sal/FP: 105 patients) from 23 centers were evaluated. Approximately 25% of patients showed COPD Stage IV. On average patients had suffered 2.3 ± 0.6 moderate/severe exacerbations in the preceding year. The annual rate of moderate/severe exacerbations observed in the study was similar in both treatment groups (SFC: 0.86 ± 0.13; Sal/FP: 0.86 ± 0.14; exacerbation rate ratio SFC/Sal/FP: 1.00; p = 0.73; negative binomial model). Compliance was high and comparable in both groups. Besides COPD exacerbations, pneumonia (5.6%) and nasopharyngitis (5.2%) were the most common adverse events.. Observed exacerbation rates were lower than those reported at baseline. No substantial difference was observed between administration of salmeterol xinafoate/fluticasone propionate via a single inhaler and separate inhalers. Treatment was safe and well tolerated. ClinicalTrials.gov Identifier: NCT00527826.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Delivery of Health Care; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Health Care Costs; Humans; Male; Medication Adherence; Middle Aged; Nebulizers and Vaporizers; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quality of Life; Salmeterol Xinafoate; Severity of Illness Index; Treatment Outcome; Vital Capacity

The combination of tiotropium and fluticasone propionate/salmeterol (FSC) is commonly used to treat chronic obstructive pulmonary disease (COPD), but no study had evaluated the effectiveness of tiotropium plus FSC with 250 μg of fluticasone propionate. Our aim was to assess whether tiotropium (18 μg once daily) plus FSC (250/50 μg twice daily) provides better clinical outcomes compared to tiotropium monotherapy.. In this 24-week, randomized, open label, multicenter two-arm parallel study, 479 patients received tiotropium plus FSC (n = 237) or tiotropium alone (n = 242).. After 24 weeks of treatment, the triple-inhaled treatment group had a significant improvement in pre-bronchodilator FEV(1) (L) compared to the tiotropium-only group (0.090 L vs. 0.038 L; P = 0.005). Regarding health-related quality of life, the mean change in total score on the St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) was -6.6 points in the tiotropium plus FSC group, but -1.5 points in the tiotropium-only group (P = 0.001). In the subgroup of GOLD stage II patients with COPD, treatment with tiotropium plus FSC also improved FEV(1) compared to tiotropium alone (0.088 L vs. 0.030 L; P = 0.011) and improved the total SGRQ-C score than tiotropium alone (-4.5 points vs. -1.0 points, respectively). This triple-inhaled treatment approach did not induce more adverse events, such as pneumonia.. Over the course of 24 weeks, FSC (250/50 μg twice daily) added to tiotropium provided greater improvement in lung function and quality of life in patients with COPD (FEV(1) ≤ 65%) than tiotropium alone.

Topics: Acute Disease; Aged; Albuterol; Algorithms; Androstadienes; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Combining maintenance medications with different mechanisms of action may improve outcomes in COPD. In this study we evaluated the efficacy and safety of fluticasone/salmeterol (FSC) (250/50 mcg twice daily) when added to tiotropium (18 mcg once daily) (TIO) in subjects with symptomatic moderate to severe COPD.. This was a 24-week, randomized, double-blind, parallel group, multi-center study. Subjects 40 years or older with cigarette smoking history ≥10 pack-years and with the diagnosis of COPD and post-bronchodilator FEV(1) ≥40 to ≤ 80% of predicted normal and FEV(1)/FVC of ≤0.70 were enrolled. Following a 4-week treatment with open-label TIO 18 mcg once daily, subjects were randomized in a double-blind fashion to either the addition of FSC 250/50 DISKUS twice daily or matching placebo. The primary efficacy endpoint was AM pre-dose FEV(1) and secondary endpoints included other measures of lung function, rescue albuterol use, health status and exacerbations.. The addition of FSC to TIO significantly improved lung function indices including AM pre-dose FEV(1), 2 h post-dose FEV(1), AM pre-dose FVC, 2 h post-dose FVC and AM pre-dose IC compared with TIO alone. Furthermore, this combination was superior to TIO alone in reducing rescue albuterol use. However, there were no significant differences between the treatment groups in health status or COPD exacerbations. The incidence of adverse events was similar in both groups.. The addition of FSC to subjects with COPD treated with TIO significantly improves lung function without increasing the risk of adverse events. NCT00784550.

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Health Status; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; United States

The aims were to determine the effect of an oral inhibitor of the signaling mediator p38 mitogen-activated protein kinase (GW856553, losmapimod) on sputum neutrophils, pulmonary function, and blood biomarkers of inflammation in chronic obstructive pulmonary disease (COPD). Three hundred and two individuals with GOLD stage II COPD were randomized to oral losmapimod 7.5 mg twice daily, inhaled salmeterol/fluticasone propionate 50 µg/500 µg combination (SFC), or placebo in a 12-week, randomized, double-blind, double-dummy study (MKI102428/NCT00642148). Neither losmapimod nor SFC had an effect on the primary end point of sputum neutrophils. Losmapimod was well tolerated and reduced plasma fibrinogen by 11% (-0.4 g/L, ratio of effect of losmapimod/placebo 0.89; 95% confidence interval, 0.83-0.96; P = .002) with nonsignificant reductions in interleukin-6, interleukin-8, and C-reactive protein. There was evidence of improvement in hyperinflation with losmapimod compared with placebo (overall P = .02). Inhaled SFC significantly improved lung function and reduced serum CC-16 (ratio of effect of SFC/placebo 0.87; 95% confidence interval, 0.82-0.93; P < .001). It was concluded that oral losmapimod significantly reduced plasma fibrinogen in patients with COPD.

Topics: Administration, Oral; Aged; Albuterol; Androstadienes; Cyclopropanes; Double-Blind Method; Drug Combinations; Female; Fibrinogen; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Neutrophils; p38 Mitogen-Activated Protein Kinases; Pulmonary Disease, Chronic Obstructive; Pyridines; Sputum

There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population. The study examined COPD patients with moderate COPD exacerbations. COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation.. This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation. A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period. A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs. COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009). COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution.. 21,524 patients with a moderate COPD exacerbation were identified. Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation. Annual costs averaged $594 per patient. A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis. The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04). After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91). The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort. However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05). Total monthly COPD-related costs, as a result, did not differ between cohorts.. Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy. Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC.

Topics: Albuterol; Androstadienes; Cholinergic Antagonists; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Health Care Costs; Humans; Middle Aged; Prevalence; Pulmonary Disease, Chronic Obstructive; Sympathomimetics; Treatment Outcome; United States

Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD.. In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations.. There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70.. Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Disease Progression; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Time Factors; Withholding Treatment

Although salmeterol/fluticasone propionate combination (SFC) therapy has been widely used for the treatment of COPD, the relationship between airway dimensions and improvement in pulmonary function remains unknown. The aim of this study was to compare the effects of SFC in combination with tiotropium (Tio) and Tio alone, on airway dimensions and pulmonary function in COPD patients.. Thirty COPD patients were randomized to receive inhaled Tio (18 µg once daily) or inhaled SFC (50/250 µg twice daily) plus Tio for 12 weeks. Spirometry and CT were performed, and the St. George's Respiratory Questionnaire (SGRQ) was completed, before and after the trial. Airway dimensions were assessed by a validated CT technique, and airway wall area (WA) corrected for body surface area (BSA), percentage wall area (WA%), absolute wall thickness T/√BSA, and luminal area Ai/BSA at the right apical segmental bronchus, were measured.. Treatment with SFC plus Tio significantly decreased WA/BSA (P < 0.05), WA% (P < 0.01) and T/√BSA (P < 0.01), and increased Ai/BSA (P < 0.01), whereas treatment with Tio alone had no effect. The changes in WA/BSA and Ai/BSA were significantly correlated with increases in FEV1 (r = 0.48, P < 0.05, and r = 0.36, P < 0.05, respectively). There were significant improvements in SGRQ scores after treatment with SFC plus Tio.. Airway wall thickening and airway narrowing decreased after treatment with SFC plus Tio, and the changes in airway dimensions were proportional to the improvements in FEV1 . These results suggest that SFC plus Tio is more effective than Tio alone in the management of COPD patients.

Topics: Aged; Aged, 80 and over; Albuterol; Androstadienes; Bronchi; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Little is known about factors that determine health status decline in clinical trials of COPD.. To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.. St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.. Data from 4951 patients in 28 countries were available. SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains. SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001). There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women. Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1. The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.. In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors. Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.. ClinicalTrials.gov: NCT00268216.

Topics: Adrenergic beta-2 Receptor Agonists; Age Factors; Aged; Albuterol; Androstadienes; Asia; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Europe; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Health Status; Health Status Indicators; Humans; Lung; Male; Middle Aged; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Quality of Life; Risk Assessment; Risk Factors; Salmeterol Xinafoate; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; United States

COPD is associated with increased arterial stiffness which may in part explain the cardiovascular morbidity observed in the disease. A causal relationship between arterial stiffness and cardiovascular events has not been established, though their strong association raises the possibility that therapies that reduce arterial stiffness may improve cardiovascular outcomes. Prior studies suggest that fluticasone propionate/salmeterol (FSC) may improve cardiovascular outcomes in COPD and we hypothesized that FSC would reduce arterial stiffness in these patients.. This multicenter, randomized, double-blind, placebo-controlled study compared the effects of FSC 250/50 μg twice-daily and placebo on aortic pulse wave velocity (aPWV) as determined by ECG-gated carotid and femoral artery waveforms. The primary endpoint was aPWV change from baseline at 12-weeks (last measure for each patient).. 249 patients were randomized; the mean FEV(1) in each group was similar (55% predicted) and 60% of patients reported a cardiovascular disorder. At 12-weeks, aPWV between FSC and placebo was -0.42 m/s (95%CI -0.88, 0.03; p = 0.065). A statistically significant reduction in aPWV between FSC and placebo was observed in those who remained on study drug throughout the treatment period [-0.49 m/s (95%CI -0.98, -0.01; p = 0.045)]. A post hoc analysis suggested the effect of FSC was greater in patients with higher baseline aPWV.. FSC does not reduce aPWV in all patients with moderate to severe COPD, but may have effects in those with elevated arterial stiffness. Additional studies are required to determine if aPWV could serve as a surrogate for cardiovascular events in COPD.

Topics: Albuterol; Androstadienes; Arteries; Blood Flow Velocity; Cardiovascular Diseases; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sympathomimetics; Treatment Outcome; Vascular Resistance

Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation.. The present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control.. COPD patients with forced expiratory volume in one second <65% and plethysmographic functional residual capacity ≥120% of predicted were randomized to a double-blind, double-dummy, 12-week, parallel group, treatment with either BDP/F 400/24 μg/day or FP/S 500/100 μg/day. Lung volumes were measured with full body plethysmography, and dyspnea was measured with transition dyspnea index.. Eighteen patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F versus FP/S.. BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Androstadienes; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Dyspnea; Ethanolamines; Exercise Test; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Functional Residual Capacity; Glucocorticoids; Humans; Italy; Lung; Male; Middle Aged; Plethysmography, Whole Body; Pulmonary Disease, Chronic Obstructive; Residual Volume; Time Factors; Total Lung Capacity; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) still poses a formidable challenge to patients and clinicians alike. A fixed-dose dry powder combination inhaler, Seretide/Advair, containing salmeterol and fluticasone, is licensed in the European Community for the treatment of moderate to severe COPD in the strength of 50/500 microg twice daily (BID). Several studies have investigated the effects of this combination and show improved forced expiratory volume in 1 s (FEV(1)), quality of life, and a decrease of exacerbations. Most of the studies have run for less than 1 year. The aim of this investigator-initiated, independent study was to elucidate if the combination containing 50 microg of salmeterol and 250 microg of fluticasone BID could be shown to have the same beneficial effect as the higher dosage, and if the effect could be sustained over time.

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Cohort Studies; Cross-Over Studies; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Hospitalization; Humans; Pulmonary Disease, Chronic Obstructive; Regression Analysis; Smoking; Sweden; Time Factors; Treatment Outcome; Vital Capacity

  Airway inflammation is a known pathological feature of chronic obstructive pulmonary disease (COPD). We examined the effect of inhaled salmeterol, alone and in combination with fluticasone propionate, on the management of patients with COPD..   Forty male COPD patients were randomly divided into two groups; group 1 (n=20) were treated with long-acting ß2-agonist, and group 2 (n=20) with long-acting ß2-agonist and inhaled glucocoticoid each day for 3 months. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1s (FEV1) and peak expiratory flow (PEF), were measured at the beginning, 1 and 2 months after treatment and at the end of the study. The frequency of using inhaled salbutamol/day and the 6-min walk distance were also measured at four different visits. The frequency of exacerbation was also recorded during the 90-day treatment period in the two groups..   FEV(1) , FVC and PEF were significantly higher after 30 days of treatment with fluticasone propionate (mean change from baseline in group 2: 155mL, 200mL and 70L/s, respectively; P<0.001). Six-minute walk distance also increased significantly (mean change from baseline: 160 m; P < 0.001), and there was a 70%-80% reduction in the use of inhaled salbutamol (P<0.001). All improvements were maintained over the remainder of the study period. Exacerbations over the 90-day treatment period were significantly fewer than in the same 90-day period in the previous year (2.8±0.7 vs 0.8±0.9; P<0.001). In contrast, only PEF increased significantly with treatment in group 1 (salmeterol treatment alone)..   These results indicated that inhaled corticosteroids may be beneficial in some patients with COPD.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Androstadienes; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Salmeterol Xinafoate; Treatment Outcome

Osteoporosis is common in patients with COPD, but its prevalence and progression are not well characterized. Concerns have been raised over the possible deleterious effect of long-term therapy with inhaled corticosteroids (ICSs) on bone density in this population. Here, we investigated the long-term effects of therapy with fluticasone propionate (FP) alone, salmeterol (SAL) alone, and a SAL/FP combination (SFC) on bone mineral density (BMD) and bone fractures in patients with moderate-to-severe COPD in the TOwards a Revolution in COPD Health (TORCH) study.. A randomized, double-blind, parallel-group, placebo-controlled study conducted at 88 US centers involving 658 patients (a subset of 6,184 international subjects in TORCH). Therapy with placebo, SAL (50 microg), FP (500 microg), or SFC (SAL 50 microg/FP 500 microg) twice daily was administered for 3 years. Baseline and yearly measurements of BMD at the hip and lumbar spine were performed. The incidence of traumatic and nontraumatic bone fractures was recorded.. At baseline, 18% of men and 30% of women had osteoporosis, and 42% of men and 41% of women had osteopenia based on BMD assessments. Forty-three percent of subjects completed all testing. The changes in BMD at the hip and lumbar spine over 3 years were small. No significant differences were observed between treatment arms (adjusted mean percent change from baseline at hip was -3.1% for placebo, -1.7% for SAL, -2.9% for FP, and -3.2% for SFC therapy, respectively; while, the corresponding changes for the lumbar spine were 0, 1.5%, -0.3%, and -0.3% for placebo, respectively, SAL, FP, and SFC therapy). The incidence of fractures was low and was similar for all treatments (5.1% to 6.3%).. Osteoporosis is highly prevalent in patients with COPD, irrespective of gender. In the TORCH study, no significant effect on BMD was detected for ICS therapy compared with placebo.. ClinicalTrials.gov Identifier: NTC00268216.

Topics: Aged; Albuterol; Androstadienes; Bone Density; Bone Diseases, Metabolic; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Fractures, Bone; Humans; Male; Middle Aged; Osteoporosis; Prevalence; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Risk Factors; Salmeterol Xinafoate; Treatment Outcome; United States

Topics: Aged; Airway Obstruction; Albuterol; Androstadienes; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Inflammation; Pulmonary Disease, Chronic Obstructive; Substance Withdrawal Syndrome

Patients with chronic obstructive pulmonary disease (COPD) often experience symptoms and problems with activities early in the morning. This is the first study to compare the effect of budesonide/formoterol and salmeterol/fluticasone on lung function, symptoms and activities early in the morning.. Lung function (peak expiratory flow [PEF] and forced expiratory volume in 1 second [FEV( 1)]) and symptoms were measured at bedside and activities were measured during the morning using a six-item questionnaire concerning basic morning routines. In a randomised, double-blind, multicentre, cross-over study, 442 patients with COPD aged >or=40 years (pre-bronchodilator FEV(1)

Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Surveys and Questionnaires

Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function. This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting beta2-agonists, formoterol and salmeterol.. This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study. Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 microg) and salmeterol/fluticasone (50/500 microg), separated by a 4-14-day washout period. ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients. The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects.. Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 microM x hr versus 6.21 microM x hr) and fluticasone (0.84 microM x hr versus 1.50 microM x hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point). In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 microM versus 0.09 microM). The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006). Both treatments were well tolerated.. The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar. In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide.. Trial registration number NCT00379028.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Area Under Curve; Biological Availability; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; England; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Receptors, Adrenergic, beta-2; Severity of Illness Index; Sputum; Sweden; Young Adult

International guidelines recommend the long-acting anticholinergic, tiotropium, or long-acting beta 2-agonists as maintenance therapy in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The efficacy of long-acting beta(2)-agonists combined with inhaled corticosteroids (ICS) in the treatment of COPD has also been confirmed for severe and very severe COPD, but data comparing tiotropium with the combination of a long-acting beta 2-agonist and an ICS are lacking.. This 6-week multicentre, randomised, double-blind, triple-dummy pilot study compared the bronchodilator effects of tiotropium 18 microg once daily (n=56) vs. the combination of salmeterol 50 microg plus fluticasone 250 microg twice daily (n=51) in patients with moderate-to-very severe COPD. Serial spirometry was performed over 12h after 6 weeks of treatment. The primary endpoint was forced expiratory volume in 1s (FEV1) area under the curve from 0 to 12h (AUC0-12h) on Day 43.. Randomization failed to provide treatment groups with comparable baseline characteristics for smoking history, current smokers, duration of COPD, FEV1, forced vital capacity (FVC) and reversibility. Mean+/-SD FEV1 was 1.31+/-0.47 l in the tiotropium group vs. 1.46+/-0.53 l in the salmeterol plus fluticasone group. Fewer patients in the tiotropium showed a 12% and 200 ml acute increase to short-acting bronchodilators at baseline. However, treatment with tiotropium alone resulted in comparable bronchodilation compared with salmeterol plus fluticasone, as measured by all the spirometric parameters at the end of the 6-week study period. FEV1 AUC0-12h was 1.55+/-0.03 l in the tiotropium group vs. 1.57+/-0.04 l in the salmeterol plus fluticasone groups (p=0.63). Trough (predose) FEV1 was 1.54+/-0.03 l in the tiotropium group vs. 1.46+/-0.03 l in the combination group (p=0.07), and peak FEV(1) was 1.68+/-0.04 l vs. 1.66+/-0.04 l, respectively, (p=0.77). FVC AUC0-12h, trough and peak were also comparable between groups at study end (p>0.05, for all). Further, rescue salbutamol use was similar in the tiotropium and combination groups and both treatment regimens were well tolerated.. Six weeks of treatment with tiotropium resulted in comparable bronchodilation compared with salmeterol plus fluticasone in patients with moderate-to-very severe COPD, despite tiotropium patients having lower lung function and fewer patients considered reversible at baseline. The results of this pilot study will aid planning for further large-scale comparative studies.

Topics: Adult; Albuterol; Androstadienes; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide

Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease (COPD).. We compared the relative efficacy of the long-acting inhaled bronchodilator/antiinflammatory combination (salmeterol/fluticasone propionate) 50/500 microg twice daily and the long-acting bronchodilator (tiotropium) 18 microg once daily in preventing exacerbations and related outcomes in severe and very severe COPD.. A total of 1,323 patients (mean age, 64 yr, post-bronchodilator FEV1, 39% predicted) were randomized in this 2-year, double-blind, double-dummy parallel study.. Primary endpoint was health care utilization exacerbation rate. Other endpoints included health status measured by St. George's Respiratory Questionnaire (SGRQ), mortality, adverse events, and study withdrawal. Probability of withdrawing from the study was 29% greater with tiotropium than salmeterol/fluticasone propionate (P = 0.005). The modeled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio, 0.967; 95% confidence interval [CI], 0.836-1.119]; P = 0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionate versus tiotropium (difference 2.1 units; 95% CI, 0.1-4.0; P = 0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3%) of patients in this group died compared with 38 (6%) in the tiotropium group (P = 0.032). More pneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (P = 0.008).. We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study while receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate-treated patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00361959).

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Secondary Prevention; Survival Rate; Tiotropium Bromide

Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD).. To determine the effect of inhaled corticosteroids with or without long-acting beta(2)-adrenergic agonist on systemic biomarkers of inflammation.. We conducted a double-blind randomized placebo-controlled trial across 11 centers (n = 289 patients with FEV(1) of 47.8 +/- 16.2% of predicted) to compare the effects of inhaled fluticasone alone or in combination with salmeterol against placebo on circulating biomarkers of systemic inflammation over 4 weeks. The primary endpoint was C-reactive protein (CRP) level. Secondary molecules of interest were IL-6 and surfactant protein D (SP-D).. Neither fluticasone nor the combination of fluticasone/salmeterol had a significant effect on CRP or IL-6 levels. There was, however, a significant reduction in SP-D levels with fluticasone and fluticasone/salmeterol compared with placebo (P = 0.002). Health status also improved significantly in both the fluticasone and fluticasone/salmeterol groups compared with placebo, driven mostly by improvements in the symptom scores. Changes in the circulating SP-D levels were related to changes in health status scores. FEV(1) improved significantly only in the fluticasone/salmeterol group compared with placebo.. ICS in conjunction with long-acting beta(2)-adrenergic agonist do not reduce CRP or IL-6 levels in serum of patients with COPD over 4 weeks. They do, however, significantly reduce serum SP-D levels. These data suggest that these drugs reduce lung-specific but not generalized biomarkers of systemic inflammation in COPD.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Biomarkers; C-Reactive Protein; Canada; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Interleukin-6; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Surfactant-Associated Protein D; Respiratory Function Tests; Treatment Outcome

The aim of this pilot study was to explore the relative efficacy in terms of improvement in symptoms and lung function of combining fluticasone propionate/salmeterol combination (FSC) and tiotropium in patients with severe-to-very severe stable COPD. Ninety patients were randomized to receive 3 months of treatment in one of three treatment groups: (1) FSC 500/50 microg Diskus, 1 inhalation twice daily+placebo Handihaler 1 inhalation once-daily daily; (2) tiotropium 18 microg Handihaler, 1 inhalation once daily+placebo Diskus, 1 inhalation twice daily; (3) FSC 500/50 microg Diskus, 1 inhalation twice daily+tiotropium 18 microg Handihaler, 1 inhalation once-daily daily. Patients attended the clinic before and after 1 month, 2 months, and 3 months of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using a visual analog scale (VAS). Also the supplemental salbutamol use was measured. Eighty-one patients completed the 3-month treatment period: 26 patients receiving FSC, 26 patients receiving tiotropium, and 29 patients receiving FSC+tiotropium. Patients were withdrawn for COPD exacerbation. Improvements in trough FEV(1) with all treatments medications were observed by the first month when trough FEV(1) had improved significantly above baseline by 74 mL (p<0.05) in the tiotropium group, by 117 mL (p<0.05) in the FSC group and by 115 mL (p<0.05) in FSC+tiotropium group. At the end of the study, trough FEV(1) had improved significantly above baseline by 141 mL (p<0.05) in the tiotropium group, by 140 mL (p<0.05) in the FSC group and by 186 mL (p<0.05) in FSC+tiotropium group. The difference between FSC and tiotropium appeared to decrease, that between FSC and FSC+tiotropium appeared to increase and that between tiotropium and FSC+tiotropium remained almost similar with study duration. Our results suggest that adding FSC and tiotropium may provide benefits in symptomatic patients with severe-to-very severe stable COPD.

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Data on the onset of action of COPD medications are lacking. This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate-to-severe COPD and reversible airway obstruction.. In this double-blind, double-dummy, crossover study, 90 patients (aged >or=40 years; FEV(1) 30-70% predicted) were randomized to a single dose (two inhalations) of budesonide/formoterol 160/4.5 microg, salmeterol/fluticasone 25/250 microg, salbutamol 100 microg or placebo (via pressurized metered-dose inhalers) on four visits. The primary end-point was change in FEV(1) 5 min after drug inhalation; secondary end-points included inspiratory capacity (IC) and perception of onset of effect.. Budesonide/formoterol significantly improved FEV(1) at 5 min compared with placebo (P < 0.0001) and salmeterol/fluticasone (P = 0.0001). Significant differences were first observed at 3 min. Onset of effect was similar with budesonide/formoterol and salbutamol. Improvements in FEV(1) following active treatments were superior to placebo after 180 min (all P < 0.0001); both combinations were better than salbutamol at maintaining FEV(1) improvements (P

Topics: Adrenal Cortex Hormones; Adult; Aged; Airway Obstruction; Albuterol; Androstadienes; Anti-Asthmatic Agents; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Spirometry; Time Factors

Chronic obstructive pulmonary disease (COPD) is recognized as a major healthcare problem in the United States and around the world.. This survey regarding initial experience in patients with COPD collected feedback about newly initiated therapy with fluticasone propionate/salmeterol (FSC; ADVAIR DISKUS).. Three telephone surveys were conducted; Survey 1 prior to initiating therapy with FSC 250/50, and Surveys 2 and 3 at 2 weeks and 30 days after initiating therapy with FSC 250/50, respectively.. One thousand primary care physicians recruited outpatients into the trial.. Patients were either newly diagnosed with COPD associated with chronic bronchitis or were still experiencing breathing difficulties on an anticholinergic medication.. Patients initiated FSC 250/50 and received a 1-month supply of FSC 250/50 with an albuterol inhaler for rescue use.. Outcome measures were patient perceptions of satisfaction, compliance, and convenience and changes in breathing on 1 (negative) to 9 (positive) point scales.. Five hundred sixteen patients completed all 3 surveys. The mean age was 61 years, 63% were female, and 62% had been diagnosed with COPD associated with chronic bronchitis for 3 years or less (Table 1).. Patients reported high satisfaction, compliance, and convenience with FSC 250/50 within 2 weeks of initiating therapy, all maintained over the trial period. Additionally, patients had positive changes in breathing, including improvements in the ability to breathe upon awakening in the morning.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Bronchitis, Chronic; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Patient Satisfaction; Pulmonary Disease, Chronic Obstructive

To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD.. This was a randomized, double-blind, parallel-group study.. Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal.. Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50.. A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50.. We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Dyspnea; Female; Fluticasone-Salmeterol Drug Combination; Humans; Lung; Lung Volume Measurements; Male; Middle Aged; Physical Endurance; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Respiratory Function Tests; Respiratory Mechanics; Salmeterol Xinafoate; Tidal Volume; Time Factors

Long-acting beta(2)-agonists (LABAs) are recommended in the management of patients with chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated that the LABA, salmeterol, improves lung function, symptoms and quality of life in patients with COPD. In this study, we have performed additional analyses of the combined data from two previous double-blind, placebo-controlled, parallel studies of salmeterol (50 microg, b.i.d) in patients with COPD. The new analyses reveal that the significant improvements seen in pre-dose and 2-h post-dose forced expiratory volume in 1 s (FEV(1)) compared to placebo, occur early in the treatment period, and are sustained for at least 24 weeks. Moreover, improvements in peak expiratory flow rate occur as early as Day 1, and are sustained throughout the 24-week period. Additional analyses of 12-h FEV(1) data also show that salmeterol is associated with an increase in the area under the curve at Week 12 compared with Day 1, adding further support to evidence that it results in a sustained bronchodilator response, with no evidence of tolerance.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Equipment and Supplies; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Time Factors

The pathology of chronic obstructive pulmonary disease (COPD) includes both obstructive and inflammatory components.. The aim of this study was to confirm the findings of a previous study that compared the efficacy of a combination of 2 short-acting bronchodilators with the use of an inhaled corticosteroid and a long-acting beta-agonist in the treatment of COPD.. We conducted an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group study of subjects with moderate to severe COPD to compare fluticasone propionate/salmeterol 250/50 microg BID (FSC) with ipratropium/albuterol 36/206 microg QID (IB/ALB). The primary efficacy measure was morning preadministration forced expiratory volume in 1 second (FEV(1)). Secondary measures were morning peak expiratory flow (PEF), 6-hour FEV(1) AUC, percentage of symptom-free nights, Transition Dyspnea Index (TDI) score, and overall daytime symptom score. Additional measures included sleep symptoms, supplemental albuterol use, and nighttime awakenings due to respiratory symptoms. Safety evaluations were based on clinical adverse events and COPD exacerbations.. Baseline characteristics were similar between the FSC (n = 180) and IB/ALB (n = 181) groups, including mean age (63.7 and 65.4 years, respectively), mean body weight (81 and 79 kg, respectively), screening pulmonary function (mean [SD], 43.7% [14.2%] and 41.6% [13.4%] of predicted FEV(1)), race (82% and 91% white), and sex (64% and 62% male). FSC resulted in greater improvements in morning preadministration FEV(1), morning PEF, and 6-hour FEV(1) AUC (all, P < 0.001), TDI score (P = 0.026), overall daytime symptom score (P = 0.024), percentage of symptom-free nights (P = 0.010), nighttime awakenings due to respiratory symptoms (P = 0.002), sleep symptom score (P = 0.003), and percentage of days and nights without rescue albuterol use compared with IB/ALB (P = 0.021 and P < 0.001, respectively). Compared with day 1, the FEV(1) AUC at week 8 increased by 0.38 L-h with FSC and decreased by 0.18 L-h with IB/ALB (P < 0.001 between groups). The type and incidence of adverse events were similar between the 2 groups. One or more adverse event was reported for 81 (45%) and 85 (47%) subjects in the FSC and IB/ALB groups, respectively.. In this 8-week study, subjects with moderate to severe COPD experienced greater improvements in lung function and symptom measures with FSC than with IB/ALB.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Area Under Curve; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Ipratropium; Male; Middle Aged; Peak Expiratory Flow Rate; Pulmonary Disease, Chronic Obstructive

The aim of this study was to compare the relative efficacy in terms of improvement in symptoms and lung function of salmeterol/fluticasone propionate (SLM/FP) combination administered through the Diskus inhaler versus theophylline (THEO) added to FP Diskus in patients with stable chronic obstructive pulmonary disease (COPD).. Eighty patients were randomized to receive 4 months of treatment in one of two treatment groups: (1) fixed combination of SLM 50 microg and FP 500 microg Diskus, 1 inhalation twice daily; or (2) FP Diskus 500 microg, 1 inhalation twice daily, plus oral titrated THEO twice daily. Patients attended the clinic before and after 4, 8, 12 and 16 weeks of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using an analogic visual scale. Also the supplemental salbutamol use was measured.. . Sixty-six patients completed the 4-month treatment period: 37 patients receiving SLM/FP and 29 patients receiving THEO+FP. Patients were withdrawn for various reasons, the most common of which were poor compliance with the protocol, exacerbation and GI events. A gradual increase in FEV(1) was observed with each treatment. Maximum significant increases in FEV(1) over baseline values that were observed after 4 months of treatment were as follows: SLM/FP 0.172 l (95% CI: 0.084-0.260) and THEO+FP 0.155 l (95% CI: 0.054-0.256). SLM/FP experienced significantly (p<0.05) greater improvements in dyspnea, and required significantly fewer supplemental salbutamol treatments than the THEO+FP group.. Our results suggest that SLM/FP combination may provide substantial benefits in both physiologic and clinical outcomes in symptomatic patients with COPD. It also causes a more effective control than THEO+FP.

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Smoking; Theophylline

This randomized controlled trial examined the benefits of combining an inhaled corticosteroid, fluticasone propionate (F), with an inhaled long-acting beta(2)-agonist, salmeterol (S), to treat the inflammatory and bronchoconstrictive components of chronic obstructive pulmonary disease (COPD). A total of 691 patients with COPD received the combination of F and S (FSC), S (50 mcg), F (500 mcg), or placebo twice daily via the Diskus device for 24 weeks. A significantly greater increase in predose FEV(1) at the endpoint was observed after FSC (156 ml) compared with S (107 ml, p = 0.012) and placebo (-4 ml, p < 0.0001). A significantly greater increase in 2-hour postdose FEV(1) at the endpoint was observed after treatment with FSC (261 ml) compared with F (138 ml, p < 0.001) and placebo (28 ml, p < 0.001). There were greater improvements in the Transition Dyspnea Index with FSC (2.1) compared with F (1.3, p = 0.033), S (0.9, p < 0.001), and placebo (0.4, p < 0.0001). The incidence of adverse effects (except for an increase in oral candidiasis with FSC and F) was similar among the treatment groups. We conclude that FSC improved lung function and reduced the severity of dyspnea compared with individual components and placebo.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Powders; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siV. There were no significant changes in pre-dose siV. In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Beclomethasone; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glycopyrrolate; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive

Apart from the individual diseases, some patients also show overlapping manifestations of asthma and COPD. Nevertheless, the diagnosis of COPD is often delayed due to inaccessibility to spirometry; the prevalence of the asthma COPD overlap phenotype is rather high given the exposure to biomass smoke. Furthermore, the rates of exacerbations are twice as high compared to the patients with either of the diseases. A treatment strategy that would reduce the risk of exacerbations would contribute immensely to the management of such patients. Evidence of eosinophilia (marker of inflammation) in patients with asthma, asthma COPD overlap phenotype or COPD alone should prompt treatment with a combination of inhaled corticosteroids (ICS)/ long-acting β-agonists (LABA); several studies have shown improvement in the airflow limitation and reduction in the rate of exacerbations with salmeterol-fluticasone combination (SFC). Considering the association of COPD and cardiovascular diseases (CVD), it is critical to determine the cardiovascular safety of the LABA in such patients. Salmeterol is a highly selective partial b-2 agonist; the TORCH study and the studies comparing formoterol and salmeterol infer that there is no increased risk of new cardiovascular adverse events either with Salmeterol or SFC. Furthermore, the combination may provide certain degree of cardio-protection. Since COPD per se increases the risk of CVD, the cardio-safety of salmeterol outweighs its onset of action. SFC has well substantiated benefits in patients with asthma, COPD and high-risk patients such as those with an overlap of COPD and asthma symptoms, patients with elevated eosinophils and pre-existing CVD. An advisory board was hence conducted, which discussed the role of combination of salmeterol and fluticasone (SFC) not only in asthma and COPD but also in asthma COPD overlap phenotype. Based on the panel's clinical experience and the expertise derived thereof, the propositions regarding the place of SFC therapy in patients with stable and uncontrolled asthma, asthma COPD overlap phenotype and COPD has been put forth.

Topics: Asthma; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial.We performed a historical cohort study (2000-2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 1:1 matching to TORCH participants, as follows. Control group 1: people with COPD not prescribed fluticasone propionate (FP)-salmeterol (SAL); control group 2: people with COPD prescribed SAL only. FP-SAL exposed groups were then selected from CPRD by propensity score matching to each control group. Outcomes studied were COPD exacerbations, death from any cause and pneumonia.2652 FP-SAL exposed people were propensity score matched to 2652 FP-SAL unexposed people while 991 FP-SAL exposed people were propensity score matched to 991 SAL exposed people. Exacerbation rate ratio was comparable to TORCH for FP-SAL

Topics: Administration, Inhalation; Androstadienes; Bronchodilator Agents; Cohort Studies; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Treatment Outcome

Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β. Can comparative effectiveness and safety of LABA plus LAMA (LABA/LAMA) and LABA plus ICS (LABA/ICS) FDCs vary by different individual components of the dual combinations in COPD?. We conducted a new user, propensity score-inverse probability of treatment weighting cohort study to compare the effectiveness and safety of two frequently used LABA/LAMA FDCs (indacaterol plus glycopyrronium [IND/GLY] and vilanterol plus umeclidinium [VI/UMEC]) vs three commonly prescribed LABA/ICS FDCs (salmeterol plus fluticasone propionate [SAL/FP], formoterol fumarate plus budesonide [FF/BUD], and formoterol fumarate plus beclomethasone dipropionate [FF/BDP]) using the Taiwanese nationwide health care claims from 2014 through 2017. The primary effectiveness outcome was the annual moderate to severe exacerbation rate, and safety outcomes included risks of severe pneumonia and cardiovascular disease requiring hospitalization. Weighted generalized linear mixed models and Cox proportional hazard models were used to assess the effectiveness and safety outcomes, respectively.. Patients with COPD initiating IND/GLY and VI/UMEC showed an 11% (incidence rate ratio [IRR], 0.89; 95% CI, 0.80-0.98) and 20% (IRR, 0.80; 95% CI, 0.71-0.90) reduced annual rate of moderate to severe exacerbations, respectively, than those initiating SAL/FP, but showed a similar rate as those initiating FF/BUD or FF/BDP. Both LABA/LAMA FDCs, compared with SAL/FP and VI/UMEC vs FF/BDP, were associated with a 27% (hazard ratio [HR], 0.73; 95% CI, 0.59-0.90) to 42% (HR, 0.58; 95% CI, 0.48-0.70) reduced pneumonia risk. Cardiovascular risk was comparable in five groups. An intraclass difference existed in rates of moderate to severe COPD exacerbation and risks of pneumonia among LABA/ICS FDCs, but not between LABA/LAMA FDCs.. Both LABA/LAMAs vs SAL/FP are associated with a lower exacerbation rate and pneumonia risk, but exhibit similar effectiveness and safety outcomes compared with FF/BDP or FF/BUD, suggesting that comparative effects may differ by individual components of the dual therapies in COPD.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Beclomethasone; Benzyl Alcohols; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Cohort Studies; Comparative Effectiveness Research; Disease Progression; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Muscarinic Antagonists; Pneumonia; Propensity Score; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Quinolones; Quinuclidines

Topics: Bronchodilator Agents; Clarithromycin; Fluticasone-Salmeterol Drug Combination; Humans; Neural Networks, Computer; Pulmonary Disease, Chronic Obstructive; Tomography, X-Ray Computed

Previous studies have found suboptimal control of symptom burden to be widespread among patients with asthma and chronic obstructive pulmonary disease (COPD). The Phase IV SPRINT study was conducted in 10 countries in Europe to assess asthma disease control and COPD symptom burden in patients treated with a fixed-dose combination (FDC) of inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs). SPRINT included 1101 patients with asthma and 560 with COPD; all were receiving treatment with an FDC of ICS/LABA, delivered via various inhalers. Data were obtained over a 3-month period, during a single routine physician's office visit. Asthma control was defined as Asthma Control Test (ACT) score >19. COPD symptom burden was assessed by COPD Assessment Test (CAT), with a CAT score <10 defining low COPD symptom burden. Among patients using any ICS/LABA FDC, 62% of patients with asthma had achieved disease control (ACT score >19) and 16% of patients with COPD had low symptom burden (CAT score <10).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Dry Powder Inhalers; Europe; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Treatment Outcome

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.. 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).. 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.. 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.

Topics: Bronchodilator Agents; Cost-Benefit Analysis; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Markov Chains; Pulmonary Disease, Chronic Obstructive; Quinolones; Sweden; Treatment Outcome

To investigate the incidence of active tuberculosis (TB) among COPD patients using fluticasone/salmeterol or budesonide/formoterol, and to identify any differences between these two groups of patients.. The study enrolled COPD patients from Taiwan NHIRD who received treatment with fluticasone/salmeterol or budesonide/formoterol for > 90 days between 2004 and 2011. The incidence of active TB was the primary outcome.. Among the intention-to-treat population prior to matching, the incidence rates of active TB were 0.94 and 0.61% in the fluticasone/salmeterol and budesonide/formoterol groups, respectively. After matching, the fluticasone/salmeterol group had significantly higher rates of active TB (adjusted HR, 1.41, 95% CI, 1.17-1.70) compared with the budesonide/formoterol group. The significant difference between these two groups remained after a competing risk analysis (HR, 1.45, 95% CI, 1.21-1.74). Following propensity score matching, the fluticasone/salmeterol group had significantly higher rates of active TB compared with the budesonide/formoterol group (adjusted HR, 1.45, 95% CI, 1.14-1.85). A similar trend was observed after a competing risk analysis (HR, 1.44, 95% CI, 1.19-1.75). A higher risk of active TB was observed in the fluticasone/salmeterol group compared with the budesonide/formoterol group across all subgroups, but some differences did not reach statistical significance.. Fluticasone/salmeterol carried a higher risk of active TB compared with budesonide/formoterol among COPD patients.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Budesonide, Formoterol Fumarate Drug Combination; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Mycobacterium tuberculosis; Propensity Score; Pulmonary Disease, Chronic Obstructive; Risk Factors; Taiwan; Tuberculosis

COPD-diagnosed Medicare Advantage enrollees aged ≥65 years were identified from the Optum Research Database (ORD). Eligible patients had ≥1 pharmacy claim for UMEC/VI or FP/SAL in the 6-month period before sample identification, with no evidence of triple therapy (ICS/LAMA/LABA), asthma, or lung cancer. Symptom burden was assessed via cross-sectional surveys using the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Patients were classified into GOLD categories using patient-reported symptoms and claims-based exacerbation history. Treatment groups were balanced on potential confounders using inverse probability of treatment weighting (IPTW). CAT and mMRC scores were analyzed with generalized linear regression models using IPTW propensity scores.. The final analytic sample included 789 respondents (UMEC/VI: N=392; FP/SAL: N=397). Approximately 66% patients were classified as GOLD B when assessing symptoms with CAT and mMRC together, or CAT alone; more patients were classified as GOLD A (~40%) than GOLD B (~36%) using mMRC alone. Proportions of patients in each GOLD group were similar between treatment cohorts. Post-IPTW multivariable modeling showed similar symptom burden between treatment groups.. After controlling for baseline characteristics, symptom burden was similar between patients receiving UMEC/VI or FP/SAL. GOLD classification using mMRC produced more conservative results compared with CAT, potentially underestimating patient symptoms. Many patients receiving FP/SAL were classified as GOLD A or B, despite GOLD recommending non-ICS-containing therapy in these patients. These findings support the need for routine assessment of symptoms in patients with COPD.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Cross-Sectional Studies; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Medicare Part C; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Treatment Outcome; United States

This study aimed to compare the effect of budesonide/formoterol and fluticasone/salmeterol on the risk and outcomes of sepsis in COPD patients. We conducted this study using the Taiwan National Health Insurance Research Database. We included COPD patients prescribed with budesonide/formoterol or fluticasone/salmeterol between 2004 and 2011. Outcomes including sepsis and mortality were measured. 10,267 COPD patients who received fluticasone/salmeterol and 6,844 patients who received budesonide/formoterol were enrolled into this study and then subsequence were adjusted by propensity score weighting. The incidence of sepsis was 5.74 and 4.99 per 100 person-years for the patients receiving fluticasone/salmeterol and budesonide/formoterol, respectively. Fluticasone/salmeterol was associated with higher risk of sepsis (aHR, 1.15; 95%CI, 1.07-1.24) and septic shock (aHR, 1.14; 95%CI, 1.01-1.29) than budesonide/formoterol. Besides, fluticasone/salmeterol was associated with higher risk of death (aHR, 1.090; 95%CI, 1.01-1.18) than budesonide/formoterol. Patients receiving fluticasone/salmeterol had a significant higher risk of sepsis related respiratory organ dysfunction, lower respiratory tract infection, genitourinary tract infection, bacteremia and skin infection. In conclusion, long-term treatment with budesonide/formoterol was associated with lower rates of sepsis and deaths than fluticasone/salmeterol in patients with COPD.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Incidence; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sepsis

Clinical trials of COPD pharmacotherapy typically involve aging populations with moderate-to-severe COPD, but the latter is often diagnosed by spirometric criteria that are not age-appropriate across the continuum of lung function. We have therefore re-evaluated the clinical effect of combination therapy (salmeterol plus fluticasone) in moderate-to-severe COPD, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI) and trial data from Towards a Revolution in COPD Health (TORCH).. Of the 6112 TORCH participants, 5688 (93.1%) had GLI-based moderate-to-severe COPD (mean age 64.8 years). The primary outcome was all-cause mortality and the primary comparison was combination therapy vs. placebo. Secondary outcomes included COPD and cardiovascular (CV) mortality and pneumonia. A modified intention-to-treat analysis evaluated differences in time-to-event over a three-year period, using Cox proportional hazards models with statistical significance at p < 0.010 (acknowledging repeated significance testing).. Relative to placebo, combination therapy yielded a statistically non-significant reduction in all-cause mortality-adjusted hazard ratio [adjHR] 0.78 (95% confidence interval [CI]: 0.64, 0.95), p = 0.012. Relative to placebo, combination therapy also yielded statistically non-significant reductions in COPD and CV mortality-adjHR 0.75 (95% CI: 0.55, 1.02), p = 0.068 and adjHR 0.76 (95% CI: 0.53, 1.09), p = 0.135, respectively. In contrast, combination therapy yielded a statistically significant increased risk of pneumonia, relative to placebo-adjHR 1.80 (95% CI: 1.46, 2.21), p < 0.001.. In GLI-based moderate-to-severe COPD, combination therapy yields a statistically significant increased risk of pneumonia but the reductions in mortality are not statistically significant, although could potentially be clinically meaningful.

Topics: Aged; Bronchodilator Agents; Cardiovascular Diseases; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Multicenter Studies as Topic; Pneumonia; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Severity of Illness Index; Spirometry

In light of the growing evidence base for better clinical results with the use of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) over inhaled corticosteroid-containing salmeterol/fluticasone combination (SFC), this study aimed to evaluate the cost-effectiveness of IND/GLY over SFC in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at low risk of exacerbations, in the Singapore healthcare setting.. A previously published patient-level simulation model was adapted for use in Singapore by applying local unit costs. The model was populated with clinical data from the LANTERN and ECLIPSE studies. Both costs and health outcomes were predicted for the lifetime horizon from a payer's perspective and were discounted at 3% per annum. Costs were expressed in 2015 USD exchange rates. Uncertainty was assessed through probabilistic sensitivity analysis.. Compared to SFC, use of IND/GLY increased mean life expectancy by 0.316 years and mean quality-adjusted life years (QALYs) by 0.246 years, and decreased mean total treatment costs (drug costs and management of associated events) by USD 1,474 over the entire lifetime horizon. IND/GLY was considered to be 100% cost-effective at a threshold of 1 × gross domestic product per capita. The cost-effectiveness acceptability curve showed that IND/GLY was 100% cost-effective at a willingness-to-pay threshold of USD 0 (additional cost) when compared to SFC.. IND/GLY was estimated to be highly cost-effective compared to SFC in patients with moderate-to-severe COPD who are not at high risk of exacerbations in the Singapore healthcare setting.

Topics: Aged; Bronchodilator Agents; Cohort Studies; Computer Simulation; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glycopyrrolate; Hospitals; Humans; Indans; Male; Middle Aged; Probability; Pulmonary Disease, Chronic Obstructive; Quality-Adjusted Life Years; Quinolones; Singapore

To examine the clinical and economic outcomes associated with the use of long-acting bronchodilators for initial maintenance treatment of chronic obstructive pulmonary disease (COPD) by analyzing health insurance claims data in the US.. A retrospective, observational, matched cohort study used health insurance claims data (January 2008 to June 2013) to assess COPD-related outcomes for subjects aged ≥40 years. Subjects were assigned to a study cohort according to the first observed prescription fill for a long-acting bronchodilator (fluticasone propionate 250 mcg/salmeterol 50 mcg [FSC] or tiotropium bromide 18 mcg [TIO]). The analysis period for each subject comprised a 1-year pre-index date and 1-year post-index date. Primary outcome measure was total COPD-related costs per-patient per-year (PPPY) during the follow-up period. Secondary outcome measures included COPD-related exacerbations and the components of COPD-related costs.. Overall, 24,040 subjects were identified; the analysis sample consisted of 19,090 subjects (9,545 per cohort) with no significant differences between cohorts. Mean COPD-related total costs PPPY were numerically lower among the FSC cohort; however, the difference was not statistically significant ($2,224 [±4,108] vs $2,352 [±3,721], p = .057). There was no difference between cohorts for COPD-related medical costs (p = .894). COPD-related pharmacy costs were significantly, yet modestly, lower in the FSC cohort compared with the TIO cohort ($1,160 [±1,106] vs 1,275 [±1,110], p < .001). There were no statistically significant differences in the rate or number of exacerbations between the matched cohorts.. While propensity scoring achieved balance in baseline characteristics, some residual confounding unobserved in the database may be present.. Few clinical and economic differences between subjects initiating maintenance therapy with FSC or TIO were observed.

Topics: Age Factors; Aged; Aged, 80 and over; Bronchodilator Agents; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Health Expenditures; Humans; Insurance Claim Review; Male; Managed Care Programs; Middle Aged; Models, Econometric; Pulmonary Disease, Chronic Obstructive; Residence Characteristics; Retrospective Studies; Severity of Illness Index; Sex Factors; Tiotropium Bromide

This combination of fluticasone propionate (FP) and the long-acting β2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course. Therefore, this combination may be more effective than inhaled steroids for patients with a history of COPD.. This patient suffered adverse reactions triggered by methylprednisolone: weight gain, hyperglycaemia and sleep disturbance after more than two months of intravenous and oral prednisolone. These reactions disappeared when we switched the patients to FP/Salm maintenance therapy.. The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (UICC) (7th edition).One month after repeat radiotherapy, the patient experienced fever (37.6°C), cough, chest distress and shortness of breath. We performed serologic tests, laboratory tests for procalcitonin and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe. These radiographic signs are typical of RP. Since the patient required oxygen, he was diagnosed with grade III RP.. After the patinet was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration and prevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60  per day. And we cut the steroid dose in half every one week when the patient's symptoms improved obviously, and the patchy shadow on the chest radiograph sharply reduced. Then we give him FP (500 mg)/Salm (50 mg) twice daily for two months. Then the dose was halved for an additional two months.. The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018.. This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP.

Topics: Adrenergic beta-2 Receptor Agonists; Anti-Inflammatory Agents; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Lung; Lung Neoplasms; Male; Methylprednisolone; Middle Aged; Pneumonectomy; Pulmonary Disease, Chronic Obstructive; Radiation Pneumonitis; Tomography, X-Ray Computed; Treatment Outcome

Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818). Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001). Improvements were observed in reducing FEV. Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations. Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.. GlaxoSmithKline (study number: 202067). Plain language summary available for this article.

Topics: Aged; Benzyl Alcohols; Chlorobenzenes; Disease Progression; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Randomized Controlled Trials as Topic; Respiratory System Agents; Secondary Prevention; Symptom Assessment; Treatment Outcome

Chronic obstructive pulmonary disease (COPD) represents an illness with significant healthcare and societal impacts. Fixed combinations of long-acting beta-agonists (LABA) and inhaled corticosteroids have been used for COPD treatment as the standard of care for many years. A daily dose of indacaterol and glycopyrronium (IND/GLY) at 110/50 µg has recently been gaining attention due to its improved efficacy and tolerability versus the standard of care.The study aims to evaluate the cost-effectiveness of once daily IND/GLY vs. twice daily salmeterol/fluticasone propionate (SFC) at 50/500 µg in COPD patients.. A microsimulation model in MS Excel was adapted to the Czech setting. Effectiveness data and disease severity stages were obtained from the FLAME study, which is a head-to head trial comparing IND/GLY vs. SFC. Quality of life data were derived from a literature review. Costs (medication, monitoring and complications) were taken from published Czech sources. The incremental cost-effectiveness ratio (ICER) was expressed as cost per quality-adjusted life year (QALY) gained. Costs and outcomes were discounted at 3 %. A lifetime horizon was used for the analysis. Cost-effectiveness was studied from the perspective of a health care system in the Czech Republic.. Mean QALYs were higher in the IND/GLY arm (difference 0.167 QALYs). The ICER of IND/GLY compared with SFC was €13,628 per QALY gained. Deterministic sensitivity analyses and probabilistic sensitivity analyses confirmed the base-case result to be robust.. From the perspective of the Czech health care system, managing COPD using IND/GLY is cost-effective in this analysis because the base-case is clearly below the willingness-to-pay threshold in the Czech Republic, which is automatically set at 3 times GDP/capita (approximately €44,000/ QALY). This is the first available economic analysis utilizing FLAME study results in the Central East European (CEE) countries showing IND/ GLY as a highly cost-effective investment into COPD patients.

Topics: Bronchodilator Agents; Cost-Benefit Analysis; Czech Republic; Female; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Male; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quality-Adjusted Life Years; Quinolones

Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA) prescriptions, for COPD patients initiating fluticasone propionate (FP)/salmeterol xinafoate (SAL) via pMDI versus DPI at two doses of FP (500 and 1,000 μg/d) using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 μg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%]) versus DPI (115 [49%]) (adjusted rate ratio: 0.71; 95% confidence interval: 0.54, 0.93), an important result since the pMDI is not licensed for COPD in the UK, USA, or China. At 1,000 μg/d, we observed lower LAMA prescription for pMDI (adjusted odds ratio: 0.71; 95% confidence interval: 0.55, 0.91), but no difference in exacerbation rates, potentially due to higher dose of ICS overcoming low lung delivery from the DPI.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Comparative Effectiveness Research; Databases, Factual; Disease Progression; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Logistic Models; Lung; Male; Metered Dose Inhalers; Middle Aged; Muscarinic Antagonists; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; United States

It remains unclear whether severe exacerbation and pneumonia of COPD differs between patients treated with budesonide/formoterol and those treated with fluticasone/salmeterol. Therefore, we conducted a comparative study of those who used budesonide/formoterol and those treated with fluticasone/salmeterol for COPD.. Subjects in this population-based cohort study comprised patients with COPD who were treated with a fixed combination of budesonide/formoterol or fluticasone/salmeterol. All patients were recruited from the Taiwan National Health Insurance database. The outcomes including severe exacerbations, pneumonia, and pneumonia requiring mechanical ventilation (MV) were measured.. During the study period, 11,519 COPD patients receiving fluticasone/salmeterol and 7,437 patients receiving budesonide/formoterol were enrolled in the study. Pairwise matching (1:1) of fluticasone/salmeterol and budesonide/formoterol populations resulted in to two similar subgroups comprising each 7,295 patients. Patients receiving fluticasone/salmeterol had higher annual rate and higher risk of severe exacerbation than patients receiving budesonide/formoterol (1.2219/year vs 1.1237/year, adjusted rate ratio, 1.08; 95% CI, 1.07-1.10). In addition, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia than patients receiving budesonide/formoterol (12.11 per 100 person-years vs 10.65 per 100 person-years, adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.20). Finally, patients receiving fluticasone/salmeterol had higher incidence rate and higher risk of pneumonia requiring MV than patients receiving budesonide/formoterol (3.94 per 100 person-years vs 3.47 per 100 person-years, aHR, 1.14; 95% CI, 1.05-1.24). A similar trend was seen before and after propensity score matching analysis, intention-to-treat, and as-treated analysis with and without competing risk.. Based on this retrospective observational study, long-term treatment with fixed combination budesonide/formoterol was associated with fewer severe exacerbations, pneumonia, and pneumonia requiring MV than fluticasone/salmeterol in COPD patients.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Databases, Factual; Disease Progression; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Logistic Models; Lung; Male; Middle Aged; Pneumonia; Propensity Score; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Respiration, Artificial; Retrospective Studies; Risk Factors; Severity of Illness Index; Taiwan; Time Factors; Treatment Outcome

Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management.. Data on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days' wages it would cost the least paid public servant were analysed.. The availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days' wages for inhaled salbutamol to 17.1 days' wages for formoterol/budesonide inhalers and 27.8 days' wages for spirometry.. Medicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Diagnostic Techniques, Respiratory System; Drug Combinations; Drug Costs; Fluticasone-Salmeterol Drug Combination; Health Services Accessibility; Humans; Leukotriene Antagonists; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Spirometry; Uganda

Topics: Benzyl Alcohols; Chlorobenzenes; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Pulmonary Disease, Chronic Obstructive

The potential consequences of confounding due to drug formulary restrictions in pharmacoepidemiologic research remain incompletely understood. Our objective was to illustrate this potential bias using the example of fluticasone/salmeterol combination therapy, an oral inhaler used to treat asthma and chronic obstructive pulmonary disease, whose use is restricted in the province of Quebec, Canada.. We identified all new users of fluticasone/salmeterol in Quebec's administrative databases and classified those who received their initial dispensing of fluticasone/salmeterol between 1 September 1999 and 30 September 2003 as users from the liberal period and those who received it between 1 January 2004 and 31 October 2006 as users from the restricted period. The primary outcome was time to first hospitalization for respiratory causes within 12 months of cohort entry.. Our cohort included 72 154 new users from the liberal period and 5058 from the restricted period. Compared with use during the liberal period, use during the restricted period was associated with an increased rate of hospitalization for respiratory causes (crude hazard ratio [HR] = 1.41, 95% confidence interval [CI] = 1.32, 1.51). Subsequent adjustment for age, sex, and hospitalization for respiratory causes in the previous year attenuated the association (HR = 1.05, 95%CI = 0.98, 1.12). Further adjustment for other potential confounders resulted in a lower rate during the restricted period (HR = 0.78, 95%CI = 0.73, 0.83).. Formulary restrictions can result in substantial and unexpected confounding and should be considered during the design and analysis of pharmacoepidemiologic studies.

Topics: Asthma; Bronchodilator Agents; Cohort Studies; Confounding Factors, Epidemiologic; Databases, Factual; Drug Utilization Review; Fluticasone-Salmeterol Drug Combination; Formularies as Topic; Hospitalization; Humans; Mortality; Outcome Assessment, Health Care; Pharmacoepidemiology; Pulmonary Disease, Chronic Obstructive; Quebec; Retrospective Studies

Topics: Benzyl Alcohols; Chlorobenzenes; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Pulmonary Disease, Chronic Obstructive

This is a proof of concept study that aims to establish feasibility and safety of a new strategy that includes an action plan for early treatment of acute exacerbations of COPD (AECOPD) with doubling dose of a combination of a long-acting beta2 agonist and an inhaled corticosteroid, and to explore its potential for avoiding the requirement of prednisone and its safety. Thirty-seven COPD outpatients with previous exacerbations were enrolled and followed-up for 12 months. The written action plan included a standing prescription to be used in the event of an AECOPD: Antibiotic, for 5 days (for purulent exacerbations) and doubling a combination of Salmeterol and Fluticasone Propionate for 10 days. The primary outcome was "treatment success" defined as "no need of prednisone within 30 days of the onset." Twenty-seven patients experienced an AECOPD and doubled their combination dose. Among the 27 patients, there were 21 patients (78%) who did not require prednisone, and none of those had cardiovascular events, pneumonia, ER and hospital admissions. We have assessed that an early treatment of AECOPD with doubling the dose of a combination of Salmeterol and Fluticasone Propionate appears to be safe, well-tolerated and adhered to, and results in no requirement of systemic corticosteroid in a large proportion of patients presenting with mild-to-moderate worsening of dyspnea. This trial has the potential to change the approach of treatment of AECOPD and reduce the use of oral corticosteroids.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Anti-Bacterial Agents; Clinical Protocols; Disease Progression; Dyspnea; Early Medical Intervention; Feasibility Studies; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Medication Adherence; Middle Aged; Proof of Concept Study; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

The combined therapy of inhaled corticosteroids and long-acting beta-2 agonists for mechanically ventilated patients with COPD has never been explored. Therefore, the aim of this study was to investigate their dynamic effects on lung mechanics and gas exchange.. Ten mechanically ventilated patients with resolution of the causes of acute exacerbations of COPD were included. Four puffs of salmeterol 25 μg/fluticasone 125 μg combination therapy were administered. Lung mechanics, including maximum resistance of the respiratory system (Rrs), end-inspiratory static compliance, peak inspiratory pressure (PIP), plateau pressure, and mean airway pressure along with gas exchange function were measured and analyzed.. Salmeterol/fluticasone produced a significant improvement in Rrs and PIP after 30 minutes. With regard to changes in baseline values, salmeterol/fluticasone inhalation had a greater effect on PIP than Rrs. However, the therapeutic effects seemed to lose significance after 3 hours of inhaled corticosteroid/long-acting beta-2 agonist administration.. The combination of salmeterol/fluticasone-inhaled therapy in mechanically ventilated patients with COPD had a significant benefit in reducing Rrs and PIP.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Bronchodilator Agents; Drug Monitoring; Female; Fluticasone-Salmeterol Drug Combination; Humans; Lung; Male; Pilot Projects; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Respiration, Artificial; Respiratory Function Tests; Taiwan; Treatment Outcome

We investigated changes in gene expression that occur in chronic obstructive pulmonary disease (COPD) after corticosteroid treatment and sought to identify the mechanisms that regulate these changes. Biopsy samples were taken from patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage I to II) before and after treatment with fluticasone propionate (FP)/salmeterol (SM) (50/500, 4 wk). Gene expression was measured by microarray and was confirmed by real-time reverse transcription-quantitative PCR (RT-qPCR). The effect of FP on IgG expression and B-cell proliferation in the presence of oxidative stress was also studied. FP/SM significantly increased the expression of 180 genes while repressing 343 genes. The top 5 down-regulated genes were associated with immunoglobulin production, whereas the immunomodulatory FK506 binding protein (FK506BP) was up-regulated. Genes including IL6, IL8, and TBET-encoding TBX21 were unaffected. FP reduced IgG protein and mRNA expression and proliferation of human B cells through the dephosphorylation of ERK-1/2 via increased DUSP1 (dual-specificity protein phosphatase 1) expression. Consistent with in vivo data, oxidative stress did not prevent FP-induced suppression of IgG expression in human B cells in vitro Changes in expression were validated by RT-qPCR and by gene set enrichment analysis in distinct COPD cohorts. FP may reduce the adaptive immune response in COPD and may be more effective in patients with an increased B-cell/antibody response indicated by high autoantibody titers.-Lee, J., Machin, M., Russell, K. E., Pavlidis, S., Zhu, J., Barnes, P. J., Chung, K. F., Adcock, I. M., Durham, A. L. Corticosteroid modulation of immunoglobulin expression and B-cell function in COPD.

Topics: Adult; Aged; B-Lymphocytes; Bronchodilator Agents; Cell Line; Cell Proliferation; Female; Fluticasone-Salmeterol Drug Combination; Gene Expression Regulation; Glucocorticoids; Humans; Immunoglobulins; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Oxidative Stress; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Transcriptome

Chronic obstructive pulmonary disease (COPD) affects approximately 15 million people in the United States and accounts for approximately $36 billion in economic burden, primarily due to medical costs. To address the increasing clinical and economic burden, the Global Initiative for Chronic Obstructive Lung Disease emphasizes the use of therapies that help prevent COPD exacerbations, including inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA).. To evaluate health care costs and utilization among COPD patients newly initiating ICS/LABA combination therapy with budesonide/formoterol (BFC) or fluticasone/salmeterol (FSC) in a managed care system.. COPD patients aged 40 years and older who initiated BFC (160/4.5 μg) or FSC (250/50 μg) treatment between March 1, 2009, and March 31, 2012, were identified using claims data from major U.S. health plans. BFC and FSC patients were propensity score matched (1:1) on age, sex, prior asthma diagnosis, prior COPD-related health care utilization, and respiratory medication use. COPD-related, pneumonia-related, and all-cause costs and utilization were analyzed during the 12-month follow-up period. Post-index costs were assessed with generalized linear models (GLMs) with gamma distribution. Health care utilization data were analyzed via logistic regression (any event vs. none) and GLMs with negative binomial distribution (number of visits) and were adjusted for the analogous pre-index variable as well as pre-index characteristics that remained imbalanced after matching.. After matching, each cohort had 3,697 patients balanced on age (mean 64 years), sex (female 52% BFC and 54% FSC), asthma and other comorbid conditions, prior COPD-related health care utilization, and respiratory medication use. During the 12-month follow-up, COPD-related costs averaged $316 less for BFC versus FSC patients ($4,326 vs. $4,846; P = 0.003), reflecting lower inpatient ($966 vs. $1,202; P < 0.001), pharmacy ($1,482 vs. $1,609; P = 0.002), and outpatient/office ($1,378 vs. $1,436; P = 0.048) costs, but higher emergency department ($257 vs. $252; P = 0.033) costs. Pneumonia-related health care costs were also lower on average for BFC patients ($2,855 vs. $3,605; P < 0.001). Similarly, initiating BFC was associated with lower all-use health care costs versus initiating FSC ($21,580 vs. $24,483; P < 0.001, respectively). No differences in health care utilization were found between the 2 groups.. In this study, although no difference was observed in rates of health care utilization, COPD patients initiating BFC treatment incurred lower average COPD-related, pneumonia-related, and all-cause costs versus FSC initiators, which was driven by cumulative differences in inpatient, outpatient, and pharmacy costs.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; United States

Combination treatment with an inhaled corticosteroid and long-acting beta2-agonist is among the many treatment options for chronic obstructive pulmonary disease (COPD) that has been shown to improve clinical outcomes. While mometasone/formoterol does not currently have an FDA-approved indication for COPD, evidence from 2 phase 3 trials demonstrated that mometasone/formoterol can improve lung function and was well tolerated in patients with moderate-to-very severe COPD. Based on these data, a therapeutic interchange was implemented in the Kaiser Permanente Mid-Atlantic States region to convert patients with a COPD diagnosis from fluticasone/salmeterol to mometasone/formoterol.. To evaluate the impact of a therapeutic interchange from fluticasone/salmeterol to mometasone/formoterol on health outcomes in patients with COPD in a large ambulatory and managed care setting.. The investigators retrospectively reviewed the electronic medical records of patients with a COPD diagnosis who had a prescription for fluticasone/salmeterol converted to mometasone/formoterol between March 6, 2011, to March 6, 2013. Kaiser Permanente's Pharmacy and Therapeutics Committee provided recommended equivalent doses for conversion from fluticasone/salmeterol to mometasone/formoterol. Nonetheless, the final approval for the change in medication and selection of the dose was left to each physician's clinical judgment. Patients were excluded if they were (a) prescribed fluticasone/salmeterol 100/50 mcg, which has no equivalent mometasone/formoterol dose; (b) less than aged 18 years; or (c) prescribed fluticasone/salmeterol for a duration of less than 6 months preconversion to mometasone/formoterol. In addition, patients who left the Kaiser Permanente network or became deceased during the study period of interest were excluded. After the application of the inclusion and exclusion criteria, 521 patients were included in the data analysis. The primary endpoint was the determination of the difference in the occurrence of COPD exacerbations 6 months pre- and postconversion from fluticasone/salmeterol to mometasone/formoterol. COPD exacerbations were defined by the diagnosis or documentation of a COPD exacerbation during any hospitalizations, urgent care (UC)/emergency department (ED) visits, or clinic encounters. Secondary outcomes included the determination of the difference in the occurrence of intensive care unit admissions, hospitalizations, UC/ED visits, and clinic encounters for COPD exacerbations 6 months pre- and postconversion; number of patients who required modification in therapy; and any reasons for mometasone/for-moterol discontinuation postconversion. Patients served as their own controls to compare any differences in outcomes while taking mometasone/formoterol versus fluticasone/salmeterol.. Within our patient population, 34.2% (n = 178) of patients experienced at least 1 COPD exacerbation while prescribed fluticasone/salmeterol compared with 28.6% (n = 149) of patients while prescribed mometasone/formoterol (P = 0.030). Mometasone/formoterol therapy did not demonstrate any statistically significant differences in the secondary outcomes (P < 0.050). A later subgroup analysis of the primary outcome revealed that factors associated with a statistically significant decrease in the occurrence of COPD exacerbations were male sex (P = 0.023), comorbid asthma (P = 0.026), and conversion from fluticasone/salmeterol to a more potent dose of mometasone/formoterol (P = 0.014).. There was a statistically significant decrease in the proportion of patients who experienced COPD exacerbations postconversion from fluticasone/salmeterol to mometasone/formoterol. This study is an example of a real-world therapeutic interchange that provides additional data to support the use of mometasone/formoterol for its unlabeled COPD indication.. No outside funding supported this study. The authors report no financial or other conflicts of interest related to the subject of this article. All authors contributed to study design and manuscript revision. Yip collected and analyzed data and prepared the manuscript.

Topics: Aged; Ambulatory Care; Bronchodilator Agents; Cohort Studies; Drug Substitution; Female; Fluticasone-Salmeterol Drug Combination; Hospitalization; Humans; Male; Managed Care Programs; Middle Aged; Mometasone Furoate, Formoterol Fumarate Drug Combination; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Treatment Outcome

Topics: Adrenergic beta-2 Receptor Agonists; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones

The objective of this study was to evaluate the different outcomes associated with the use of budesonide/formoterol compared to fluticasone/salmeterol in fixed combinations in patients with COPD in a "real-world" setting. The outcomes included exacerbation rates and health care costs.. An observational retrospective cohort analysis, based on administrative databases of three local health units, was conducted. Patients with at least one prescription of fixed-dose combination of inhaled corticosteroids and long-acting β2-agonists (budesonide/formoterol or fluticasone/salmeterol), at dosages and formulations approved for COPD in Italy, between January 1, 2009 and December 31, 2011 (inclusion period), were included. Patients were followed until December 2012, death or end of treatment (follow-up period), whichever occurred first. Patients were included if they were aged ≥40 years and had at least 6 months of follow-up. Propensity score matching was performed to check for confounding effects. Number of hospitalizations for COPD and number of oral corticosteroid and antibiotic prescriptions during follow-up were analyzed using Poisson regression models. The cost analysis was conducted from the perspective of the National Health System.. Among patients with COPD, treatment with a fixed combination of budesonide/formoterol was associated with fewer exacerbations and a lower, but not significant, cost of illness than the treatment with fluticasone/salmeterol. Real-world analyses are requested to ameliorate interventions to address unmet needs, optimizing treatment pathways to improve COPD-related burden and outcomes.

Topics: Administrative Claims, Healthcare; Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Cost-Benefit Analysis; Databases, Factual; Disease Progression; Drug Costs; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Italy; Lung; Male; Middle Aged; Propensity Score; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Retrospective Studies; Time Factors; Treatment Outcome

To investigate the association between inhaled corticosteroid (ICS) exposure patterns and the risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients, we performed a nested case-control study. Between 1998 and 2010, 51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849 control subjects selected from a cohort of COPD patients using ICSs via risk-set sampling of the database constructed by the National Health Research Institutes of Taiwan. After adjusting for covariates, the current use of ICSs was associated with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.25, 95% confidence interval [CI] =1.20-1.30), and there was an increase in the OR with increase in the average daily dosage. Additionally, users of fluticasone/salmeterol, fluticasone, and either fluticasone/salmeterol or fluticasone were more likely to be at a higher risk of pneumonia (OR =1.35, 95% CI =1.28-1.41; OR =1.22, 95% CI =1.10-1.35; and OR =1.33, 95% CI =1.27-1.39, respectively). In contrast, there were no statistically significant associations between the risk of pneumonia and the use of budesonide/formoterol, budesonide, or either budesonide/formoterol or budesonide. In conclusion, ICSs are significantly associated with an increased risk of pneumonia in COPD patients. The effect is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Case-Control Studies; Cross-Sectional Studies; Databases, Factual; Female; Fluticasone-Salmeterol Drug Combination; Humans; Logistic Models; Lung; Male; Middle Aged; Odds Ratio; Pneumonia; Pulmonary Disease, Chronic Obstructive; Quality of Life; Risk Assessment; Risk Factors; Taiwan; Time Factors; Treatment Outcome

Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.. Data from LANTERN and ILLUMINATE studies were pooled and analyzed. In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 μg/50 μg or twice-daily SFC 50 μg/500 μg. End points were pre-dose trough forced expiratory volume in one second (FEV. A total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454). At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups. TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups. IND/GLY also reduced the rate of exacerbations in the pooled population. Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group.. In this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Clinical Trials, Phase III as Topic; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glycopyrrolate; Humans; Indans; Lung; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Recovery of Function; Severity of Illness Index; Spirometry; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vital Capacity

The reliability of CT assessment of regional bronchodilation is not universally accepted. In this study, using our proprietary 3D-CT software, we first examined airway inner luminal area (Ai) before and after inhalation of SFC in a group of COPD patients and then evaluated the same parameters for two sets of CT data obtained from clinically stable subjects with no intervention.. We conducted CT at deep inspiration and pulmonary function tests before and one week after inhalation of SFC in 23 COPD patients. As a non-intervention group, we used two sets of CT data obtained with one-year interval in another group of subjects who demonstrated stable pulmonary function (n=8). We measured Ai at the mid-portions of 3rd to 6th generation in 8 bronchi of the right lung, a total of 32 identical sites before and after intervention.. The average bronchodilation at all sites (ΔAi%: 28.2 ± 4.1 (SE)%) (r=0.65, p<0.001) and that of each generation significantly correlated with % improvement of FEV1 (ΔFEV1%), which increased from 1.40 ± 0.10 L to 1.58 ± 0.10 L. When subjects were classified into two groups in terms of mean ΔFEV1%, even the poor responders (ΔFEV1% <14% above baseline, n=13) displayed significantly larger ΔAi% compared with the non-intervention group (19.1 ± 4.6% versus 2.1 ± 3.9%). Inter-observer variability for overall ΔAi% was within acceptable levels.. CT can reliably detect the regional bronchodilation in 3rd to 6th generation airways when ΔFEV1 is as small as 180 ml on average. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) system (http://www.umin.ac.jp/. No. UMIN 000002668).

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Bronchi; Bronchodilator Agents; Female; Fluticasone-Salmeterol Drug Combination; Humans; Imaging, Three-Dimensional; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Respiratory Function Tests; Tomography, X-Ray Computed

To investigate the relationship between ABCB1 single-nucleotide polymorphisms and the efficacy of salmeterol/fluticasone combination (SFC) inhalation therapy for stable chronic obstructive pulmonary disease (COPD) in a Chinese Han population.. A total of 362 patients with stable COPD were recruited between July 2012 and March 2014. Based on the therapeutic effects of lung function improvement and COPD Assessment Test (CAT) scores, all patients were either placed into the effective group (n = 138) or the ineffective group (n = 224). Three common polymorphisms (rs1045642C > T, rs1128503C > T, and rs1202184A > G) in the ABCB1 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism in these patients. All data were analyzed by SPSS version 18.0 software.. The genotype and allele frequencies of the ABCB1 rs1045642C > T polymorphic locus were significantly different between the effective group and the ineffective group under the codominant, recessive, and allele models (all p < 0.05). Haplotype analysis of ABCB1 indicated that CTA (rs1045642C-rs1128503T-rs1202184A) haplotype frequencies in the effective group were significantly lower than the ineffective group (p = 0.022), but TCG (rs1045642T-rs1128503C-rs1202184G) haplotype frequencies in the effective group were significantly higher than the ineffective group (p = 0.048). Logistic regression analysis showed that smoking history and rs1045642 CT + CC/TT may be correlated with the efficacy of SFC inhalation therapy in stable COPD patients.. ABCB1 rs1045642C > T polymorphism and CTA/TCG haplotypes, as well as smoking history may influence the efficacy of SFC inhalation therapy in stable COPD patients in the Chinese Han population.

Topics: Aged; Aged, 80 and over; Asian People; ATP Binding Cassette Transporter, Subfamily B; China; Female; Fluticasone-Salmeterol Drug Combination; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

To assess, using a standard observational tool, the ability of patients to demonstrate and maintain proper inhaled medication administration techniques following pharmacist education.. Six-month observational study.. Patients' homes or adult day health center.. Patients in a Program for All-inclusive Care for the Elderly (PACE) prescribed one or more inhaled medications used at least once daily.. Instruction by on-site clinical pharmacist.. Hickey's Pharmacies Inhaler Technique assessment (score range: 0-20, higher better).. Forty-two patients were evaluated at baseline, taught proper techniques for using inhaled medications, assessed immediately following the education, and re-assessed 4-6 weeks later. The mean pre-assessment score was 14 (SD 4.5, range 0-20), the initial post-assessment score increased to 18 (SD 3, range 10-20). The second post-assessment (4-6 weeks later) score mean was 17.7 (SD 3, range 10-20). Both follow-up scores were significantly improved from baseline (p < 0.05). Multivariable analysis indicated the strongest predictors of second post-training score were: score after initial pharmacist training and being subscribed to auto-refill. These characteristics predicted ∼70% of the variance in the second score (p < 0.001).. These results indicate that education by a pharmacist combined with an auto-refill program can improve and sustain appropriate inhaler use by community-dwelling elders in a PACE program. The improved score was maintained 4-6 weeks later indicating a sustained benefit of medication administration education. Optimal inhaler use ensures optimal dosing and supports appropriate inhaler treatment in lieu of oral agents.

Topics: Administration, Inhalation; Adult Day Care Centers; Age Factors; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Drug Delivery Systems; Female; Fluticasone-Salmeterol Drug Combination; Humans; Independent Living; Male; Middle Aged; Nebulizers and Vaporizers; Outcome Assessment, Health Care; Patient Education as Topic; Pharmacists; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Inhaled corticosteroid/long-acting β2-agonist combinations and/or long-acting muscarinic antagonists are recommended first-line therapies for preventing chronic obstructive pulmonary disease (COPD) exacerbation. Comparative effectiveness of budesonide/formoterol combination (BFC, an inhaled corticosteroid/long-acting β2-agonist combination) vs tiotropium (long-acting muscarinic antagonist) in the US has not yet been studied.. Using US claims data from the HealthCore Integrated Research Environment, COPD patients (with or without comorbid asthma) ≥40 years old initiating BFC or tiotropium between March 1, 2009 and February 28, 2012 and at risk for exacerbation were identified and followed for 12 months. Patients were propensity score matched on demographics and COPD disease severity indicators. The primary outcome was time to first COPD exacerbation. Secondary outcomes included COPD exacerbation rate, health care resource utilization, and costs.. The Cox proportional hazards model for time to first exacerbation yielded a hazard ratio (HR) of 0.78 (95% CI =[0.70, 0.87], P<0.001), indicating a 22% reduction in risk of COPD exacerbation associated with initiation of BFC versus tiotropium. A post hoc sensitivity analysis found similar effects in those who had a prior asthma diagnosis (HR =0.72 [0.61, 0.86]) and those who did not (HR =0.83 [0.72, 0.96]). BFC initiation was associated with lower COPD-related health care resource utilization and costs ($4,084 per patient-year compared with $5,656 for tiotropium patients, P<0.001).. In COPD patients new to controller therapies, initiating treatment with BFC was associated with improvements in health and economic outcomes compared with tiotropium.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Asthma; Bronchodilator Agents; Budesonide; Comorbidity; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Hospitalization; Humans; Insurance Claim Reporting; Male; Middle Aged; Muscarinic Antagonists; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

A combination of long-acting anticholinergic agents (LAACs) and long-acting β2-adrenergic receptor agonist (LABA) is effective in improving lung function in chronic obstructive pulmonary disease (COPD) compared with monotherapy. However, evidence on whether this combination increases the incidence of stroke or other cardiac events remains sparse. The objective of the present study was to investigate the incidence of stroke and other cardiovascular diseases in COPD patients treated with LAAC, LABA, or a combination of the 2.We conducted this population-based study using the Taiwan National Health Insurance Research Database (1997-2008), identifying COPD patients and their prescribed medication from the International Classification of Disease, Ninth Revision codes 490-492 or 496. A multivariate Cox proportional-hazards model was used to compare the risk of stroke and other cardiovascular diseases over the 11-year period after treatment with LAAC or LABA only or in combination.Of the 596 COPD patients (mean age 70 y), 196 were treated with LAAC, 318 with LABA, and 82 were treated with a combination. The overall incidence of stroke (8.53%) significantly increased in the combination group compared with LAAC (2.04%) or LABA (1.26%) only. In the Cox regression analysis, the adjusted hazard ratio over the 11-year survey period for stroke in patients treated with the combination compared with LABA only was 1.04 (95% confidence interval, 1.06-2.99) and for LAAC, it was 0.31 (95% confidence interval, 0.02-2.32).This cohort study using a large health insurance database showed that treating patients with COPD, with a combination of LAAC and LABA, may be associated with an increased hazard of stroke compared with treatment with either agent alone. We should be particularly cautious about comedication of LAAC and LABA in patients with COPD.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Aged, 80 and over; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Cardiovascular Diseases; Cholinergic Antagonists; Cohort Studies; Delayed-Action Preparations; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Stroke; Taiwan; Tiotropium Bromide

Combination inhaled corticosteroid/long-acting bronchodilator (ICS/LABA) therapy reduces the exacerbation rate and improves spirometry and quality of life in COPD. We hypothesized that ICS/LABA therapy also improves small airway function measured by FOT.. 14 subjects with COPD were commenced on combination fluticasone propionate/salmeterol therapy for 3 months. At baseline, subjects completed the St George Respiratory Questionnaire (SGRQ) and underwent standard pulmonary function tests as well as forced oscillation technique (FOT) and single and multiple breath nitrogen washouts. All tests were repeated at the completion of 3 months of therapy.. Subjects were of mean (SD) age 65.9 years (8.4), BMI 30.0 (5.6), pack years 51.4 (21.1), post-bronchodilator FEV1% predicted 62.7 (20). At baseline, mean SGRQ total was 39.0 (17.7) and FRC% predicted 125.4 (31.3). From FOT, Rrs-total was 5.69 (1.29) cmH2O/L/s, Xrs-total -3.48 (2.16) cmH2O/L/s, EFL Index 3.51 (2.45) cmH2O/L/s. After 3 months of therapy, there were significant improvements in SGRQ score (-13.81, p < 0.0001) despite no change in FEV1 (+40 mL, p = 0.14). From FOT, total resistance (-0.63 cmH2O/L/s, p = 0.0004), reactance (+1.2 cmH2O/L/s, p = 0.013), and expiratory flow limitation (-1.21 cmH2O/L/s, p = 0.02) also improved. There were no significant changes in ventilation heterogeneity indices.. Combination therapy is associated with improvements in small airways function in COPD, despite an absence of change in FEV1. FOT may be a clinically useful marker of small airway function in COPD that is responsive to treatment.

Topics: Administration, Inhalation; Aged; Albuterol; Analysis of Variance; Androstadienes; Bronchi; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Longitudinal Studies; Nitrogen; Oscillometry; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

Poor adherence to treatment may contribute to the treatment gap in chronic obstructive pulmonary diseases (COPD). The aim of the current study was to describe the association between adherence to treatment and the risk of COPD moderate (ME) and severe (SE) exacerbations, and health care utilization.. Observational single cohort study utilizing the Quebec Provincial Health Insurance databases. All patients older than 40 years with a diagnosis of COPD between 2001 and 2010 were entered in the study cohort at the time of their first prescription for tiotropium (TIO) alone or co-administered with fluticasone propionate/salmeterol (TIO + FSC). Follow-up continued to the last known claim or death. Adherence was measured by the medication possession ratio (MPR) ≥80% and persistence defined as no treatment gap ≥30 days.. ME was defined as use of an oral corticosteroid or antibiotic, SE as COPD related hospitalization or an emergency room (ER) visit. COPD related health care resource utilization ascertained was prescription of rescue medications, ER visits, hospitalizations, intensive care unit (ICU) admissions, intubations, and general practitioner (GP) and respirologist visits.. There were 23,707 patients included in this study. Compliance and persistence with TIO for monotherapy patients were 61.1% and 47.6% respectively. For patients treated with TIO + FSC, compliance and persistence for TIO were 62.9% and 45.3% respectively, and for FSC they were 35.4% and 33.0%. Multivariate analyses showed a significant (P < 0.001) adjusted odds ratios for ME (OR(ME)) and SE (OR(SE)) for TIO compliant vs. non-compliant patients (TIO: OR(ME) = 0.543, OR(SE) = 0.712; TIO + FSC: OR(ME) = 0.436, OR(SE) = 0.570). Similarly for FSC compliance: OR(ME) = 0.546; OR(SE) = 0.749. Similar results were observed for persistence. Compliance and persistence with TIO and FSC were associated with significantly reduced rates of health care utilization.. Despite the typical limitations of an administrative database study, the results of this large population-based study have shown that reduced adherence to treatment with TIO and FSC is associated with increased risk for exacerbations and higher health care utilization in COPD patients.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Bronchodilator Agents; Disease Progression; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Glucocorticoids; Health Services; Humans; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Quebec; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

In Europe, administration of an inhaled corticosteroid (ICS) combined with a long-acting β2 agonist is approved in chronic obstructive pulmonary disease (COPD) patients with a pre-bronchodilator FEV1 < 60% predicted normal, a history of repeated exacerbations, and who have significant symptoms despite regular bronchodilator therapy. Minimal data are available on the use of the fluticasone propionate/salmeterol xinafoate combination (FSC) in the real-life COPD setting and prescription compliance with the licensed specifications.. A French observational study was performed to describe the COPD population prescribed with FSC, prescription modalities, and the coherence of prescription practices with the market authorized population. Data were collected for patients initiating FSC treatment (500 μg fluticasone propionate, 50 μg salmeterol, dry powder inhaler) prescribed by a general practitioner (GP) or a pulmonologist, using physician and patient questionnaires.. A total of 710 patients were included, 352 by GPs and 358 by pulmonologists. Mean age was over 60 years, and 70% of patients were male. More than half were retired, and overweight or obese. Approximately half were current smokers and one-third had cardiovascular comorbidities. According to both physician evaluation and GOLD 2006 classification, the majority of patients (>75%) had moderate to very severe COPD. Strict compliance by prescribing physicians with the market-approved population for dry powder inhaler SFC in COPD was low, notably in ICS-naïve patients; all three conditions were fulfilled in less than a quarter of patients with prior ICS and less than 7% of ICS-naïve patients.. Prescription of dry powder inhaler SFC by GPs and pulmonologists has very low conformity with the three conditions defining the licensed COPD population. Prescription practices need to be improved and systematic FEV1 evaluation for COPD diagnosis and treatment management should be emphasized.

Topics: Aged; Albuterol; Androstadienes; Drug Combinations; Drug Utilization; Female; Fluticasone-Salmeterol Drug Combination; France; Glucocorticoids; Guideline Adherence; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Medicine

Combinations of inhaled corticosteroids (ICSs) and long-acting β2 -agonists (LABAs) are recommended for patients with moderate and severe chronic obstructive pulmonary disease (COPD). However, it is not known whether different fixed combinations are equally effective. The aim of this study was to investigate exacerbation rates in primary care patients with COPD treated with budesonide/formoterol compared with fluticasone/salmeterol.. Patients with physician-diagnosed COPD and a record of postdiagnosis treatment with a fixed combination of budesonide/formoterol or fluticasone/salmeterol were included. Data from primary care medical records were linked to those from Swedish national hospital, drug and cause of death registers. Pairwise (1 : 1) propensity score matching was carried out at the index date (first prescription) by prescribed fixed ICS/LABA combination. Exacerbations were defined as hospitalizations, emergency visits and collection of oral steroids or antibiotics for COPD. Yearly event rates were compared using Poisson regression.. Matching of 9893 patients (7155 budesonide/formoterol and 2738 fluticasone/salmeterol) yielded two cohorts of 2734 patients, comprising 19 170 patient-years. The exacerbation rates were 0.80 and 1.09 per patient-year in the budesonide/formoterol and fluticasone/salmeterol groups, respectively (difference of 26.6%; P < 0.0001); yearly rates for COPD-related hospitalizations were 0.15 and 0.21, respectively (difference of 29.1%; P < 0.0001). All other healthcare outcomes were also significantly reduced with budesonide/formoterol versus fluticasone/salmeterol.. Long-term treatment with fixed combination budesonide/formoterol was associated with fewer healthcare utilization-defined exacerbations than fluticasone/salmeterol in patients with moderate and severe COPD.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Registries; Respiratory Function Tests; Retrospective Studies; Secondary Prevention; Time Factors; Treatment Outcome

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Pulmonary Disease, Chronic Obstructive; Quinolones; Sympathomimetics

Chronic obstructive pulmonary disease (COPD) is frequently associated with comorbid depression and anxiety. Managing COPD symptoms and exacerbations through use of appropriate and adequate pharmacotherapy in this population may result in better COPD-related outcomes.. This retrospective, observational study used administrative claims of patients aged 40 years and older with COPD and comorbid depression/anxiety identified from January 1, 2004 through June 30, 2008. Patients were assigned to fluticasone propionate/salmeterol 250/50 mcg combination (FSC) or anticholinergics (AC) based on their first (index) prescription. The risks of COPD exacerbations and healthcare utilization and costs were compared between cohorts during 1 year of follow-up.. The adjusted risk of a COPD-related exacerbation during the 1-year follow-up period was 30% higher in the AC cohort (n = 2923) relative to the FSC cohort (n = 1078) (odds ratio [OR]: 1.30, 95% confidence interval [CI]: 1.08-1.56) after controlling for baseline differences in covariates. The risks of COPD-related hospitalizations and emergency department visits were 56% and 65% higher, respectively, in the AC cohort compared with the FSC cohort. The average number of COPD-related hospitalizations during the follow-up period was 46% higher for the AC cohort compared with the FSC cohort (incidence rate ratio [IRR]: 1.46, 95% CI: 1.01-2.09, P = 0.041). The savings from lower COPD-related medical costs ($692 vs $1042, P < 0.050) kept the COPD-related total costs during the follow-up period comparable to those in the AC cohort ($1659 vs $1677, P > 0.050) although the pharmacy costs were higher in the FSC cohort.. FSC compared with AC was associated with more favorable COPD-related outcomes and lower COPD-related utilization and medical costs among patients with COPD and comorbid anxiety/depression.

Topics: Adult; Albuterol; Androstadienes; Cholinergic Antagonists; Cost of Illness; Depression; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Glucocorticoids; Hospitalization; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Treatment Outcome

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Canada; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Nebulizers and Vaporizers; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

This retrospective cohort study compared the risks of exacerbations and COPD-related healthcare costs between patients with chronic obstructive pulmonary disease (COPD) initiating tiotropium (TIO) alone and patients initiating triple therapy with fluticasone-salmeterol combination (FSC) added to TIO.. Managed-care enrollees who had an index event of ≥ 1 pharmacy claim for TIO during the study period (January 1, 2003-April 30, 2008) and met other eligibility criteria were categorized into one of two cohorts depending on their medication use. Patients in the TIO+FSC cohort had combination therapy with TIO and FSC, defined as having an FSC claim on the same date as the TIO claim. Patients in the TIO cohort had no such FSC use. The risks of COPD exacerbations and healthcare costs were compared between cohorts during 1 year of follow-up.. The sample comprised 3333 patients (n = 852 TIO+FSC cohort, n = 2481 TIO cohort). Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation (hazard ratio 0.772; 95% confidence interval [CI] 0.641, 0.930) and any exacerbation (hazard ratio 0.763; 95% CI 0.646, 0.949) and a nonsignificant reduction in COPD-related adjusted monthly medical costs.. Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation and any exacerbation over a follow-up period of up to 1 year. These improvements were gained with triple therapy at roughly equal cost of that of TIO alone.

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Disease Progression; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Risk; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

To determine clinical and economic outcomes following COPD-related hospitalization/emergency department (ED) care in patients receiving COPD maintenance therapy.. In this retrospective, observational study using administrative claims data, we identified COPD patients age ≥40 years who received maintenance therapy within 30 days of an initial COPD-related hospitalization or ED visit with: (1) fluticasone propionate/salmeterol combination (FSC 250 mcg/50 mcg) as new therapy, or (2) an anticholinergic (AC; tiotropium or ipratropium with or without albuterol). The FSC and AC patients were matched (1:3 ratio) on various baseline characteristics using propensity scores to mitigate selection bias at baseline. The proportion of patients with COPD-related healthcare events, the mean event rates, and the mean costs in the subsequent 12 months were calculated.. The FSC cohort (N = 484) had a significantly lower proportion of rehospitalized patients during follow-up than did the AC cohort (N = 1452), 3.1% versus 4.6% (P = 0.047). The mean number of rehospitalizations was 0.03 in the FSC cohort and 0.07 in the AC cohort (P = 0.001). The proportion of patients with an exacerbation resulting in an ED or physician-outpatient visit and the mean number of such visits did not differ between cohorts. Total annual COPD-related medical costs were lower for FSC than for AC ($2080 versus $2636, P = 0.006), with lower medical and higher pharmacy costs.. Patients receiving FSC as maintenance therapy following an initial COPD-related hospitalization or ED visit experienced better clinical and economic outcomes than patients receiving AC.

Topics: Adult; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Cholinergic Antagonists; Drug Combinations; Drug Costs; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Health Care Costs; Humans; Ipratropium; Male; Middle Aged; Patient Readmission; Patient Selection; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; United States

To investigate equivalency of results from multivariable regression (MR) and propensity score matching (PSM) models, observational research methods used to mitigate bias stemming from non-randomization (and consequently unbalanced groups at baseline), using, as an example, a large study of chronic obstructive pulmonary disease (COPD) initial maintenance therapy.. Patients were 32,338 health plan members, age ≥40 years, with COPD initially treated with fluticasone propionate/salmeterol combination (FSC), tiotropium (TIO), or ipratropium (IPR) alone or in combination with albuterol. Using MR and PSM methods, the proportion of patients with COPD-related health care utilization, mean costs, odds ratios (ORs), and incidence rate ratios (IRRs) for utilization events were calculated for the 12 months following therapy initiation.. Of 12,595 FSC, 9126 TIO, and 10,617 IPR patients meeting MR inclusion criteria, 89.1% (8135) of TIO and 80.2% (8514) of IPR patients were matched to FSC patients for the PSM analysis. Methods produced substantially similar findings for mean cost comparisons, ORs, and IRRs for most utilization events. In contrast to MR, for TIO compared to FSC, PSM did not produce statistically significant ORs for hospitalization or outpatient visit with antibiotic or significant IRRs for hospitalization or outpatient visit with oral corticosteroid. As in the MR analysis, compared to FSC, ORs and IRRs for all other utilization events, as well as mean costs, were less favorable for IPR and TIO.. In this example of an observational study of maintenance therapy for COPD, more than 80% of the original treatment groups used in the MR analysis were matched to comparison treatment groups for the PSM analysis. While some sample size was lost in the PSM analysis, results from both methods were similar in direction and statistical significance, suggesting that MR and PSM were equivalent methods for mitigating bias.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Albuterol; Ambulatory Care; Androstadienes; Anti-Bacterial Agents; Bronchodilator Agents; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Drug Therapy, Combination; Emergency Service, Hospital; Female; Fluticasone-Salmeterol Drug Combination; Hospitalization; Humans; Ipratropium; Linear Models; Logistic Models; Male; Middle Aged; Models, Economic; Models, Statistical; Multivariate Analysis; Muscarinic Antagonists; Odds Ratio; Propensity Score; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; United States

The predictive factors for treatment response in patients with severe chronic obstructive pulmonary disease (COPD) are unknown. We investigated predictive factors for response to fluticasone propionate/salmeterol (FSC) in severe COPD patients.. This prospective, open-label, non-comparative study included 921 adult patients with severe COPD (baseline forced expiratory volume in 1 s (FEV(1)) <50% of predicted), a history of repeated exacerbations, and symptoms despite bronchodilator treatment. FSC (500 μg/50 μg) was delivered via an inhaler, twice a day, for 12 weeks. The primary efficacy endpoint was the response rate for inspiratory capacity (IC), FEV(1), or quality of life (QoL), assessed with the Saint George's respiratory questionnaire, at week 6 and week 12.. The overall response rate to FSC at 6 and 12 weeks was 79%. The corresponding rates for FEV(1), IC, and QoL were 38%, 55%, and 62%, respectively. More than 40% of patients showed a response for IC and/or QoL without being responders for FEV(1.) Overall lung function and QoL were improved. FSC was well tolerated with a safety profile consistent with that observed previously.. Nearly 80% of patients responded to FSC treatment in this real-life study. Improvements in IC and QoL at 12 weeks revealed a clinically relevant response in patients with no improvement in FEV(1). IC reversibility to salbutamol before treatment might represent, better than FEV1, a prognostic factor of response to FSC in severe COPD. Moreover these tests are easy to perform routinely and in large numbers of patients.

Topics: Administration, Inhalation; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; France; Humans; Male; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Treatment Outcome

Randomised controlled trials (RCTs) are considered the least biased method for evaluating drug efficacy and several large long-term RCTs in chronic obstructive pulmonary disease have been published. These usually include drugs with symptomatic benefits and have significant withdrawal rates.. We aimed at examining bias due to differential withdrawal in the Towards a Revolution in COPD Health (TORCH) trial.. We did an observational study nested in the TORCH trial, a placebo-controlled trial of salmeterol/fluticasone propionate combination (SFC) therapy in chronic obstructive pulmonary disease. We included 3057 patients randomly allocated to placebo or SFC in the analyses. We examined rates of withdrawal from the study and analysed change in effect parameters over time and in relation to withdrawal, as well as medication uptake after withdrawal.. There was differential withdrawal with a significantly higher withdrawal rate from the group allocated to placebo than to SFC, 44% compared with 34%. Regardless of treatment group, withdrawal was associated with worse baseline lung function and more frequent exacerbations, leading to selection of a study population in better health than those originally recruited. As a result, annualized exacerbation rates in the first 6 months of the study compared with the last 6 months of the study decreased from 6.8 to 0.9 in the placebo group and from 3.0 to 0.8 in the SFC group. Also, use of medications under test in the study was frequent in patients after withdrawal.. Significant bias may occur in long-term RCTs of registered medications with symptomatic benefits as a result of differential withdrawal.

Topics: Albuterol; Androstadienes; Bias; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Observation; Patient Dropouts; Placebos; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic

To quantify healthcare use and costs associated with chronic obstructive pulmonary disease (COPD) among patients discharged from a COPD-related hospitalization or emergency department (ED) visit on a regimen of fluticasone propionate-salmeterol combination versus other inhaled maintenance therapies.. Retrospective cohort study.. Managed care enrollees with an index hospitalization (with a primary or secondary [ie, in the second position] diagnosis of COPD) or ED visit (with a primary diagnosis of COPD) were identified for placement into study cohorts during a 60-day period following the index date. Time to COPD-related events and healthcare costs were compared during up to 1 year of follow-up between the 2 cohorts.. The sample comprised 5677 patients (1291 in the fluticasone propionate-salmeterol cohort and 4386 in the other maintenance therapies cohort). The adjusted rate of COPD-related hospitalizations or ED visits was 35% lower in the fluticasone propionate-salmeterol cohort (P <.05). Adjusted COPD-related total (medical plus pharmacy) costs were lower in the fluticasone propionate-salmeterol cohort ($240 vs $279 per patient per month, P <.05), mostly because of lower medical costs ($113 vs $160 per patient per month, P <.05). Pharmacy costs did not differ between fluticasone propionate-salmeterol and other maintenance therapies. Results were similar in the subset of patients 65 years or older.. Initiation of fluticasone propionate-salmeterol after discharge from a COPD-related hospitalization or ED visit significantly reduced the risk of a recurrent event during the ensuing months and decreased COPD-related medical costs, without an increase in COPD-related pharmacy costs, in a real-world setting.

Topics: Aged; Albuterol; Androstadienes; Cohort Studies; Databases, Factual; Drug Combinations; Drug Costs; Emergency Service, Hospital; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Health Care Costs; Health Services; Hospitalization; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Risk Assessment

To compare, in commercially-insured individuals 240 years old, the risk of chronic obstructive pulmonary disease (COPD) exacerbations and COPD-related health care utilization and costs in patients initiating maintenance treatment with fluticasone propionate/salmeterol xinafoate 250 microg/50 microg (FSC) with those in patients initiating treatment with tiotropium bromide (TIO).. Retrospective observational cohort study.. The risk of COPD exacerbation (moderate, severe, and any), COPD-related health care utilization, and COPD-related costs (overall and by service setting) were assessed over 12 months after the initiation of treatment with FSC or TIO in commercially-insured patients > or =40 years old diagnosed with COPD.. After adjusting for covariates, treatment with FSC compared with treatment with TIO was associated with a 14% reduction in risk of severe exacerbation (p = 0.0406), defined as the occurrence of a COPD-related hospitalization; with less health care utilization across several categories of care; with 25% lower COPD-related medical costs ($1814 versus $2258 per patient, p < 0.0001); and with 10% lower COPD-related total costs ($2991 versus $3304 per patient, p < 0.0001) over a 12-month follow-up period. Pharmacy costs were equivalent between FSC and TIO.. Initiation of maintenance therapy with FSC compared with TIO was associated with significant reductions in the risk of severe exacerbations, health care utilization, and COPD-related medical and total costs. Considered in the context of other findings, these data suggest that earlier maintenance treatment with FSC offers clinical and economic benefits over maintenance treatment with TIO.

Topics: Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Cohort Studies; Drug Combinations; Drug Costs; Drug Therapy, Combination; Economics, Pharmaceutical; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Insurance Coverage; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

To compare the effectiveness of budesonide/formoterol fumarate dihydrate (BFC) and fluticasone propionate/salmeterol (FSC), two combination inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) products approved for the treatment of chronic obstructive pulmonary disease (COPD) in the US with respect to cost, therapy adherence, and related healthcare utilization. The effectiveness of these two treatments has not previously been compared in a US COPD population.. A retrospective cohort study assessed COPD-related outcomes using administrative claims data among ICS/LABA-naïve patients. Patients initiating BFC were propensity matched to FSC patients. Cost and effectiveness were measured as total healthcare expenditures, exacerbation events (hospitalizations, emergency department visits, or outpatient visits associated with oral corticosteroid or antibiotic prescription fills), and treatment medication adherence. Differences in COPD symptom control were assessed via proxy measure through claims for rescue medications and outpatient encounters.. Of the 6770 patients (3385 BFC and 3385 FSC), fewer BFC patients had claims for short-acting beta agonists (SABA) (34.7% vs 39.5%; p<0.001) and ipratropium (7.8% vs 9.8%, p<0.005) than FSC patients, but no substantial differences were seen in other clinical outcomes including tiotropium or nebulized SABA claims, COPD-related outpatient visits, or exacerbation events. There were no significant differences in total COPD-related medical costs in the 6-month period after initiation of combination therapy.. This was a retrospective observational study using claims data and accuracy of COPD diagnoses could not be verified, nor was information available on severity of disease. The results and conclusions of this study are limited to the population observed and the operational definitions of the study variables.. For most outcomes of interest, BFC and FSC showed comparable real-world effectiveness.

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Comorbidity; Costs and Cost Analysis; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Services; Humans; Male; Medication Adherence; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies

Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom.. We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents.. We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8).. FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Aged, 80 and over; Albuterol; Androstadienes; Bronchodilator Agents; Case-Control Studies; Cataract; Databases, Factual; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; General Practice; Glaucoma; Humans; Incidence; Logistic Models; Male; Middle Aged; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United Kingdom

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Fractures, Bone; Glucocorticoids; Humans; Pneumonia; Pulmonary Disease, Chronic Obstructive

To estimate the cost-effectiveness of fluticasone propionate-salmeterol combination (FSC) compared to salmeterol for maintenance therapy in severe chronic obstructive pulmonary disease (COPD).. Pooled economic analysis.. We performed an economic analysis of pooled data from two randomized clinical trials (combined N = 1554) that evaluated the effect of maintenance therapy with FSC (250/50 microg twice daily) or salmeterol (50 microg twice daily) on exacerbation rates in patients with severe COPD. We calculated exacerbation rates and applied standardized costs to exacerbation-related health care utilization reported in the trials (office, urgent care, and emergency department visits; hospitalizations; and oral corticosteroids and antibiotics) to determine cost differences between FSC and salmeterol treatment outcomes.. Annual rates of any exacerbation and moderate/severe exacerbation were lower in the FSC group than the salmeterol group (4.91 vs 5.78 and 1.32 vs 2.00 respectively, both P < 0.05). Total adjusted annual COPD related exacerbation and therapeutic costs were $4,842 (95% CI; $4,731-$4,952) in the FSC group and $5,066 (95% CI; $4,937-$5,195) in the salmeterol group.. FSC combination therapy is associated with reduced risk of any exacerbation and moderate/severe exacerbation, and incurs lower annual COPD-related health care costs compared to treatment with salmeterol. This analysis demonstrates that FSC therapy may be advantageous from both a clinical and cost-benefit standpoint for patients with severe COPD.

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Severity of Illness Index

Relative costs and utilization-related outcomes of a fluticasone propionate 250 μg + salmeterol 50 μg combination (FSC), tiotropium bromide, and ipratropium as initial maintenance therapy in COPD have not been compared in a commercially-insured population.. This retrospective, observational cohort study used health care claims data from January 2004 to June 2009 from a large administrative database for patients aged ≥40 years with COPD. Time-to-first COPD-related health care event beginning 30 days following therapy initiation with FSC (n = 16,684), ipratropium alone or in fixed dose combination with albuterol (n = 14,449), or tiotropium (n = 12,659) was estimated using Cox proportional hazard models that controlled for differences in patient demographic characteristics, health care utilization, and comorbidities at baseline. Mean adjusted costs and numbers of COPD-related health care encounters and prescription medication fills were compared among patients with 12 months of follow-up (FSC, n = 12,595; ipratropium, n = 10,617; tiotropium, n = 9126).. With FSC as the reference, risk for a COPD-related hospitalization and/or emergency department visit was significantly higher for ipratropium (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.50-1.79) and tiotropium (HR 1.29, CI 1.17-1.41). Mean adjusted 12-month COPD-related total health care costs were lower for FSC ($2068, standard deviation [SD] $1190) than for ipratropium ($2841, SD $1858) and tiotropium ($2408, SD $1511, both P <0.05). Mean number of COPD-related hospitalizations, emergency department visits, and outpatient visits associated with an oral corticosteroid or antibiotic were also lower for FSC than for ipratropium and tiotropium (all P <0.05).. In this retrospective "real-world" observational sample of COPD patients, initiating treatment with FSC was associated with significantly better clinical and economic outcomes compared with short- and long-acting anticholinergic therapy. Consistent with the goal of preventing and reducing exacerbations advocated by global guidelines, the findings suggest that initiation of maintenance treatment with FSC may afford clinical benefits at a lower cost than anticholinergic treatment.

Topics: Aged; Albuterol; Ambulatory Care; Androstadienes; Cholinergic Antagonists; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Drug Prescriptions; Emergency Medical Services; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Hospital Costs; Hospitalization; Humans; Insurance, Pharmaceutical Services; Ipratropium; Kaplan-Meier Estimate; Male; Middle Aged; Models, Economic; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Risk Assessment; Risk Factors; Scopolamine Derivatives; Time Factors; Tiotropium Bromide; Treatment Outcome; United States

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

TORCH and UPLIFT are amongst the largest and most ambitious COPD trials ever undertaken. In terms of the primary outcomes, both trials were negative. Compared with placebo, combined salmeterol and fluticasone therapy did not significantly reduce all cause mortality over 3 years in TORCH, and tiotropium did not slow the decline in lung function over 4 years in UPLIFT. Secondary outcomes from these studies strongly confirmed findings from previous trials. Monotherapy with all three drugs provided small improvements in respiratory health status and reductions in exacerbation rates with some additive effect from the salmeterol/fluticasone combination. Both salmeterol/fluticasone and tiotropium also reduced COPD hospitalization rates. The trials provide very strong evidence that the long-acting bronchodilators, salmeterol and tiotropium, are not associated with increased risk of death or major cardiovascular adverse events.

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide

Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition with high morbidity and mortality among older and disabled adults. Few studies have examined the comparative effectiveness of maintenance therapies for chronic obstructive pulmonary disease (COPD) in this vulnerable population.. The study aims to compare healthcare resource utilization associated with hospitalization or emergency department (ED) visits between FDA-approved inhaled corticosteroid/long-acting beta-agonist combinations [fluticasone propionate 250 microg/salmeterol 50 microg combination (FSC)] and anticholinergic treatments (ATC) in managed-care Medicare beneficiaries with COPD.. Data from the Integrated Health Care Information Systems (IHCIS) National Managed Care Benchmark Database was used in this retrospective, observational cohort study. The cohort consisted of managed-care Medicare beneficiaries with a diagnosis of COPD [International Classification of Disease, 9th revision, Clinical Modification (ICD-9-CM) codes 491.xx, 492.xx, or 496.xx] without evidence of comorbid asthma (ICD-9-CM 493.xx) who received treatment with FSC or ATC between 2003 and 2005. Cox proportional hazards regression models were conducted to examine the risk of all-cause and COPD-related hospitalizations and emergency department (ED) visits.. COPD patients treated with FSC had a 18% lower risk of a COPD-related hospitalization (HR = 0.82; 95% CI = 0.75, 0.89) and an ED visit (HR = 0.82; 95% CI = 0.76, 0.89) compared to patients treated with ATC. Findings were similar for all-cause utilization (hospitalization HR = 0.83; 95% CI = 0.78, 0.88; ED visit HR = 0.84; 95% CI = 0.80, 0.88).. FSC is associated with a lower risk of COPD-related exacerbation events relative to ATC in managed-care Medicare beneficiaries with COPD. Findings from this study are only generalizable to managed-care Medicare beneficiaries residing in the community.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Comoros; Cost of Illness; Drug Combinations; Emergency Service, Hospital; Female; Fluticasone-Salmeterol Drug Combination; Health Resources; Hospitalization; Hospitals; Humans; Male; Managed Care Programs; Medicare; Middle Aged; Population; Pulmonary Disease, Chronic Obstructive; United States

This retrospective analysis of data from two multi-center, randomized, double-blind, parallel group studies compared the efficacy of fluticasone propionate/salmeterol (FSC) 250/50 mcg twice daily with ipratropium bromide/albuterol (IB/ALB) 36/206 mcg four times daily in albuterol-reversible (n=320 [44%]) and non-reversible (n=399 [56%]) patients with COPD. In reversible and non-reversible patients, both treatments significantly increased FEV(1)AUC(0-6h) from baseline and the magnitude of improvement was larger in reversible patients. FSC increased FEV(1)AUC(0-6h) by 1.46+/-0.08 and 1.98+/-0.13 l-h at Day 1 and Week 8, respectively, in reversible patients, compared with 0.71+/-0.06 and 0.94+/-0.10 l-h in non-reversible patients (p<0.001). With IB/ALB, increases were 1.46+/-0.08 and 1.19+/-0.11 l-h at Day 1 in reversible patients and Week 8, respectively, and 0.89+/-0.06 and 0.74+/-0.09 l-h (p < or = 0.041) in non-reversible patients. After 8 weeks, in both the reversible and non-reversible populations, the FEV(1) AUC(0-6h) significantly increased with FSC treatment (p < or = 0.002) and significantly decreased with IB/ALB (p < or = 0.010). In both reversibility groups, improvement in Transition Dyspnea Index (TDI) scores, overall daytime diary symptom scores and nocturnal symptom measures were significantly greater with FSC treatment compared with IB/ALB (p < or = 0.044). Reversibility status was not predictive of the magnitude of reduction in symptom scores. We conclude that both reversible and non-reversible patients receive greater clinical benefit with FSC compared with IB/ALB and acute bronchodilator reversibility is not useful for differentiating patients based on symptomatic responses to FSC compared with IB/ALB.

Topics: Adrenergic beta-Agonists; Aged; Albuterol; Albuterol, Ipratropium Drug Combination; Androstadienes; Area Under Curve; Bronchodilator Agents; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Ipratropium; Male; Middle Aged; Multicenter Studies as Topic; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Respiratory Function Tests; Retrospective Studies; Severity of Illness Index; Time Factors

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Topics: Albuterol; Androstadienes; Bronchodilator Agents; Clinical Trials as Topic; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Patient Dropouts; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Topics: Albuterol; Androstadienes; Anti-Inflammatory Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Survival Rate; Tiotropium Bromide

Topics: Actuarial Analysis; Albuterol; Androstadienes; Body Mass Index; Bronchial Hyperreactivity; Bronchodilator Agents; Cardiovascular Diseases; Drug Combinations; Dyspnea; Exercise; Fluticasone-Salmeterol Drug Combination; Humans; Hypercapnia; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Risk Assessment; Smoking Cessation

COPD is a disease with a multi-component pathophysiology in which inflammation plays a key role. An anti-inflammatory effect of salmeterol (S)/fluticasone propionate (FP) combination (SFC), as demonstrated in a number of biopsy studies, may be the mechanism by which it provides a potential survival benefit in COPD patients in the TORCH study. It is possible that the molecular synergy between S and FP shown in COPD results in enhanced anti-inflammatory in the airways. This may also contribute to the reduction in exacerbations and the increase in lung function seen in the TORCH study. Alternatively, SFC may prolong survival by impacting on systemic inflammation and disease co-morbidities in COPD.

Topics: Albuterol; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Humans; Inflammation; Pulmonary Disease, Chronic Obstructive; Survival Rate

Recent retrospective studies have suggested that use of inhaled corticosteroids (ICS) may improve survival in chronic obstructive pulmonary disease (COPD), particularly when combined with a long-acting beta-agonist (LABA). However, the study methodologies have been questioned, and no study has examined the survival effect of the newer combination ICS/LABA inhalers. The goal of this project was to further examine the relationship between ICS treatment, with or without LABA, and survival in COPD. COPD patients were identified from the administrative databases of four different integrated health care delivery systems. All patients who were diagnosed with COPD between September 1, 2000 and August 31, 2001 and who had at least 3 months treatment with either a combined fluticasone/salmeterol inhaler (FSI, N=866), any ICS used with a LABA (ICS/LABA, N=525), ICS alone (N=742), LABA alone (N=531), or a short-acting bronchodilator alone (SABD, N=1832), were included. Analyses were conducted using three different analysis approaches that adjust for various biases that may affect the results. In the basic Cox proportional hazards models, use of FSI, ICS/LABA, ICS alone, and LABA alone had significant survival benefits as compared to SABD, after adjustment for differences in age, gender, comorbidities, asthma status, and disease severity (HRs 0.61 [0.45-0.83], 0.59 [0.46-0.77], 0.76 [0.61-0.95], 0.75 [0.57-0.98], respectively). Propensity score matching to reduce the clinical differences between the treatment groups versus the SABD reference group found very similar results. Nested case-control analyses, which are based on survival status instead of treatment, continued to show a significant survival benefit for FSI, ICS/LABA, and ICS alone. Treatment with FSI or another ICS with or without LABA is associated with improved survival in COPD. The treatment benefit is reproducible and is robust to application of a number of different analysis techniques designed to adjust for differences in confounding variables and for bias by indication.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Cohort Studies; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Survival Rate

Monitoring was required for the introduction of non-chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDIs) to ensure that there were no unexpected adverse events due to the new products. A postmarketing surveillance study has been conducted to evaluate the introduction of the MDI Seretide Evohaler (hydrofluoroalkane-134a inhaler containing salmeterol and fluticasone propionate).. To summarise the modified prescription-event monitoring (PEM) study conducted to evaluate the introduction of Seretide Evohaler and discuss the relevance of this type of study towards pharmacovigilance risk-management planning.. Modified PEM methodology was used to examine the introduction of Seretide Evohaler into general practice in England. Patients were identified from the first National Health Service prescriptions dispensed in England for Seretide Evohaler. One postal questionnaire was sent to the prescribing doctor, requesting demographic information, severity of the indication, concomitant medication for this condition, smoking history, event data 3 months prior to and 3 months after the first prescription for Seretide Evohaler and also reason for stopping if it had been stopped. Pregnancies, deaths and selected events were followed up. Incidence density ratios were calculated to compare event rates 3 months prior to and 3 months after the introduction of Seretide Evohaler. A matched cohort analysis examined oral corticosteroid use and hospital admissions between the pre- and post-exposure periods.. The cohort comprised 13,464 patients prescribed Seretide Evohaler, with a response rate of 62%. There was no significant difference in the length of courses of oral corticosteroid use when the pre- and post-exposure periods were compared. A matched cohort analysis showed there was no increase in the use of oral corticosteroids (relative risk [RR] 0.95; 95% CI 0.90, 0.99) or hospital admissions in the post-exposure period (RR 0.87; 95% CI 0.73, 1.04). When the number of patients with events were compared for the periods 3 months before and 3 months after exposure, fewer events were reported in the post-exposure period. There were 64 patients who experienced adverse events within an hour of using Seretide Evohaler, including one report of paradoxical bronchospasm and one of myocardial infarction with fatal outcome that were both assessed as possibly related to treatment.. The results of the study suggest that the introduction of Seretide Evohaler was generally well tolerated. The modified methodology has allowed a comparison of the event rates before and after the introduction of this CFC-free inhaler into general practice.

Topics: Adult; Aerosol Propellants; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; England; Female; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Pregnancy; Product Surveillance, Postmarketing; Pulmonary Disease, Chronic Obstructive

Current practice guidelines for the treatment of COPD recommend the use of combined inhaled corticosteroids and long-acting bronchodilators in severe and very severe patients (GOLD stages III and IV). The aim of this study was to evaluate, through a simulation model, the economic consequences of this recommendation in Italy. We developed a cost-effectiveness analysis (CEA) on five alternative therapeutic strategies (salmeterol/fluticasone, SF; formoterol! budesonide, FB; salmeterol alone, S; fluticasone alone, F; control, C). Published data on the Italian COPD population and efficacy data from international reference trials were fitted in a disease progression model based on a Markov chain representing severity stages and death. The yearly total direct costs of treating COPD patients in Italy was estimated at approximately Euro 7 billion, with a mean cost per patient per year of around Euro 2450. Mean survival of the cohort is 11.5 years. The C and F strategies were dominated (ie, are associated with worse outcomes and higher costs) by all alternatives. SF and FB were the most effective strategies, with a slight clinical superiority of SF, but they were also marginally more expensive than S. Incremental cost-effectiveness of SF vs S was Euro 679.5 per avoided exacerbation and Euro 3.3 per symptom-free day. Compared with current practice, the recommended use of combined inhaled corticosteroids and long-acting bronchodilators for severe and very severe COPD patients has the potential for improving clinical outcomes without increasing healthcare costs.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Bronchodilator Agents; Budesonide; Budgets; Computer Simulation; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Drug Therapy, Combination; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Guideline Adherence; Health Care Costs; Health Care Rationing; Humans; Italy; Markov Chains; Models, Economic; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Quality of Life; Severity of Illness Index; Treatment Outcome