Umeclidinium/vilanterol Research Articles

Effects of Direct Switching Dual Bronchodilators between Dry Powder and Soft Mist Inhalers in COPD Patients

Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years; 48 males and 5 females; GOLD 1/2/3/4 = 19/27/6/1; mMRC 0/1/2/3/4 = 14/22/12/4/1; UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.

Human medicines European public assessment report (EPAR): Anoro Ellipta (previously Anoro), umeclidinium bromide / vilanterol, Pulmonary Disease, Chronic Obstructive, Date of authorisation: 08/05/2014, Revision: 10, Status: Authorised

Human medicines European public assessment report (EPAR): Anoro Ellipta (previously Anoro), umeclidinium bromide / vilanterol, Pulmonary Disease, Chronic Obstructive, Date of authorisation: 08/05/2014, Revision: 10, Status: Authorised

The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models

BackgroundChronic obstructive pulmonary disease (COPD) is associated with high clinical and economic burden. Optimal pharmacological therapy for COPD aims to reduce symptoms and the frequency and severity of exacerbations. Umeclidinium/vilanterol (UMEC/VI) is an approved combination therapy for once-daily maintenance treatment of patients with COPD. This study evaluated the impact of delaying UMEC/VI initiation on medical costs and exacerbation risk.MethodsA retrospective analysis of patients with COPD who initiated UMEC/VI between 4/28/2014 and 7/31/2016 was conducted using the Optum Research Database. The index date was the first COPD visit after UMEC/VI available on US formulary (Commercial 4/28/2014; Medicare Advantage 1/1/2015). Patients were followed for 12 months post-index, and categorized into 12 cohorts corresponding to month (30-day period) of UMEC/VI initiation (i.e. Months 1–12) post-index. The outcomes studied during the follow up period included COPD-related and all-cause medical costs, and risk of COPD exacerbations. Marginal structural models (MSM) were used to control for time-varying confounding due to changes in treatment and severity during follow up.Results2,200 patients initiating UMEC/VI were included in the study sample. Patients’ average age was 69.3 years, 49.9% were female and 69.7% were Medicare insured. Following MSM analysis, 12-month adjusted COPD-related medical costs increased by 2.9% (95% confidence interval [CI]: 0.1–5.9%; p = 0.044) for each monthly delay in UMEC/VI initiation, with a 37.4% higher adjusted cost for patients initiating UMEC/VI in Month 12 versus Month 1 ($13,087 vs. $9524). The 12-month adjusted all-cause medical costs increased by 2.8% (95% CI: 0.6–5.2%; p = 0.013) for each monthly delay, with a 36.1% higher adjusted cost for patients initiating UMEC/VI at Month 12 versus Month 1 ($22,766 vs. $16,727). The monthly risk of severe exacerbation was significantly higher in patients who had not yet initiated UMEC/VI than those who had (hazard ratio: 1.74; 95% CI: 1.35–2.23; p < 0.001).ConclusionsPrompt use of UMEC/VI following a physician visit for COPD appears to result in economic and clinical benefits, with reductions in medical costs and exacerbation risk. Additional research is warranted to assess the benefits of initiating UMEC/VI as a first-line therapy compared with escalation to UMEC/VI from monotherapies.

The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models

Background: Chronic obstructive pulmonary disease (COPD) is associated with high clinical and economic burden. Optimal pharmacological therapy for COPD aims to reduce symptoms and the frequency and severity of exacerbations. Umeclidinium/vilanterol (UMEC/VI) is an approved combination therapy for once-daily maintenance treatment of patients with COPD. This study evaluated the impact of delaying UMEC/VI initiation on medical costs and exacerbation risk. Methods: A retrospective analysis of patients with COPD who initiated UMEC/VI between 4/28/2014 and 7/31/2016 was conducted using the Optum Research Database. The index date was the first COPD visit after UMEC/VI available on US formulary (Commercial 4/28/2014; Medicare Advantage 1/1/2015). Patients were followed for 12 months post-index, and categorized into 12 cohorts corresponding to month (30-day period) of UMEC/VI initiation (i.e. Months 1–12) post-index. The outcomes studied during the follow up period included COPD-related and all-cause medical costs, and risk of COPD exacerbations. Marginal structural models (MSM) were used to control for time-varying confounding due to changes in treatment and severity during follow up. Results: 2,200 patients initiating UMEC/VI were included in the study sample. Patients’ average age was 69.3 years, 49.9% were female and 69.7% were Medicare insured. Following MSM analysis, 12-month adjusted COPD-related medical costs increased by 2.9% (95% confidence interval [CI]: 0.1–5.9%; p = 0.044) for each monthly delay in UMEC/VI initiation, with a 37.4% higher adjusted cost for patients initiating UMEC/VI in Month 12 versus Month 1 ($13,087 vs. $9524). The 12-month adjusted all-cause medical costs increased by 2.8% (95% CI: 0.6–5.2%; p = 0.013) for each monthly delay, with a 36.1% higher adjusted cost for patients initiating UMEC/VI at Month 12 versus Month 1 ($22,766 vs. $16,727). The monthly risk of severe exacerbation was significantly higher in patients who had not yet initiated UMEC/VI than those who had (hazard ratio: 1.74; 95% CI: 1.35–2.23; p &lt; 0.001). Conclusions: Prompt use of UMEC/VI following a physician visit for COPD appears to result in economic and clinical benefits, with reductions in medical costs and exacerbation risk. Additional research is warranted to assess the benefits of initiating UMEC/VI as a first-line therapy compared with escalation to UMEC/VI from monotherapies.

ECONOMIC IMPACT OF EARLY USE OF UMEC/VI COMPARED WITH LATER USE IN PATIENTS WITH COPD

SESSION TITLE: Obstructive Lung Diseases 1 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Umeclidinium/vilanterol (UMEC/VI) is a combination therapy for once-daily maintenance treatment of airflow obstruction in patients with COPD. UMEC/VI was shown in clinical trials to improve lung function compared to either LAMA or ICS/LABA; yet, there has been no research on the economic impact of this newer therapy, specifically if earlier use results in lower medical cost. The objective of this study was to determine if patients treated as soon as possible with UMEC/VI following a COPD-related physician visit had reduced medical costs compared with patients treated later with UMEC/VI. METHODS: A retrospective analysis of patients with COPD who initiated UMEC/VI between 4/28/2014 to 7/31/2016 was conducted using the Optum Research Database. As the focus was initiation of therapy, the index date was the first COPD visit with a potential prescriber after UMEC/VI was available in the US and on formulary (Commercial 4/28/2014; Medicare Advantage 1/1/2015). Patients were followed for 12-months post-index, and stratified into twelve cohorts corresponding to the month of UMEC/VI treatment initiation following the index date (i.e. Months 1 to 12). Patients initiating >12 months post-index were excluded. Two measures of medical costs were examined for the 12-month period: all cause and COPD-related. Marginal structural models (MSM) were used to adjust for changes in treatment and severity over time, which can impact both the exposure of interest (initiation of UMEC/VI) and the outcome. RESULTS: 2,200 patients initiated UMEC/VI. Patients’ average age was 69.3 years, half were female and 30% commercially insured. In unadjusted analysis, there were no differences in 12-month costs by month of UMEC/VI initiation. After adjustment using MSMs, all-cause medical costs were estimated to increase by 2.8% (95% CI: 0.6%-5.2%; p=0.013) for each month delay. Patients who started UMEC/VI in Month 1 had 12-month predicted all-cause medical costs of $16,727 versus $22,766 for patients who started therapy in Month 12. COPD-related medical costs increased 2.9% (95% CI: 0.1%-5.9%; p=0.044) for each month delay, with 12-month predicted COPD-related medical cost of $9,524 among patients initiating UMEC/VI therapy in Month 1 versus $13,087 for those initiating in Month 12. CONCLUSIONS: The benefit of LAMA/LABA treatment shown in clinical trials and supported by the 2017 GOLD report appears to result in an economic benefit of lower annual medical costs over a 12-month period when initiating therapy earlier compared with a delay in starting therapy. CLINICAL IMPLICATIONS: These results suggest that patients benefit from initiation of therapy with UMEC/VI as soon as possible following a physician visit for COPD. DISCLOSURES: Employee relationship with Optum Please note: $20001 - $100000 Added 02/28/2018 by Amy Anderson, source=Web Response, value=Salary Employee relationship with Optum Please note: >$100000 Added 02/28/2018 by Lee Brekke, source=Web Response, value=Salary Employee relationship with Optum Please note: >$100000 Added 03/06/2018 by Ami Buikema, source=Web Response, value=Salary Employee relationship with GlaxoSmithKline Please note: >$100000 Added 02/28/2018 by Beth Hahn, source=Web Response, value=Salary Employee relationship with Optum Please note: $20001 - $100000 Added 03/01/2018 by Eleena Koep, source=Web Response, value=Salary Employee relationship with Glaxosmithkline Pharmaceuticals Please note: >$100000 Added 02/28/2018 by Riju Ray, source=Web Response, value=Shares Removed 02/28/2018 by Riju Ray, source=Web Response Employee relationship with Glaxosmithkline Pharmaceuticals Please note: >$100000 Added 02/28/2018 by Riju Ray, source=Web Response, value=Salary Employee relationship with Glaxosmithkline Pharmaceuticals Please note: $5001 - $20000 Added 02/28/2018 by Riju Ray, source=Web Response, value=Shares Employee relationship with Optum Please note: >$100000 Added 02/28/2018 by Lucie Sharpsten, source=Web Response, value=Salary Employee relationship with GlaxoSmithKline Please note: >$100000 Added 02/28/2018 by Richard Stanford, source=Web Response, value=Salary Employee of Optum relationship with Optum, inc. Please note: $20001 - $100000 Added 03/05/2018 by Damon Van Voorhis, source=Web Response, value=Salary

Efficacy of Umeclidinium/Vilanterol in Elderly Patients with COPD: A Pooled Analysis of Randomized Controlled Trials.

ObjectiveThe aim of this pooled analysis was to assess the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg dual bronchodilation versus placebo in elderly symptomatic patients with chronic obstructive pulmonary disease (COPD).MethodsWe conducted a post hoc pooled analysis of data from 10 randomized controlled trials (RCTs). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), proportion of FEV1 responders (≥ 100-mL increase from baseline), and safety were analyzed in patients aged < 65, ≥ 65, and ≥ 75 years on Days 28, 56, and 84 (12-week analysis of parallel-group design studies), Days 28, 56, 84, 112, 140, 168, and 169 (24-week analysis of parallel-group design studies), and Days 2, 42, and 84 (12-week analysis of crossover design studies).ResultsThe UMEC/VI intent-to-treat (ITT) populations comprised 2246, 1296, and 472 patients in the 12-week parallel-group, 24-week parallel-group, and 12-week crossover analysis, respectively (≥ 65 years: 36–44%; ≥ 75 years: 7–11%). The placebo ITT populations comprised 528, 280, and 505 patients, respectively (≥ 65 years: 37–41%; ≥ 75 years: 5–11%). Significant improvements in trough FEV1 and significantly greater proportions of FEV1 responders were seen with UMEC/VI compared with placebo in all analyses regardless of patient age or timepoint considered (p ≤ 0.023), except Day 84 trough FEV1 CFB in the 12-week crossover analysis in patients aged ≥ 75 years (p = 0.064). UMEC/VI safety profile was similar to placebo in all age groups.ConclusionsIn this pooled analysis of RCT data, once-daily UMEC/VI was well tolerated and provided clinically significant lung function benefits compared with placebo in younger and older patients with COPD.FundingGlaxoSmithKline (study 208125).Electronic supplementary materialThe online version of this article (10.1007/s40266-018-0558-y) contains supplementary material, which is available to authorized users.

Umeclidinium/Vilanterol Versus Tiotropium/Olodaterol in Maintenance-Naïve Patients with Moderate Symptomatic Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis.

IntroductionAppropriate timing for dual bronchodilator therapy initiation in chronic obstructive pulmonary disease (COPD) management is uncertain. Combination therapy is recommended as step-up from monotherapy or first-line treatment in patients with persistent symptoms. In this setting, umeclidinium/vilanterol (UMEC/VI) demonstrated improved lung function and reduced rescue medication use over tiotropium/olodaterol (TIO/OLO). This subgroup analysis explored efficacy differences between these combinations in patients naïve to COPD maintenance therapy before study entry.MethodsPost hoc analysis of an 8-week, randomized, open-label, assessor-blind, two-period crossover study (204990; NCT02799784) comparing UMEC/VI 62.5/25 mcg and TIO/OLO 5/5 mcg, focused on maintenance-naïve (MN) patients with moderate COPD and persistent symptoms (modified Medical Research Council dyspnea score ≥ 2). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), percentage of FEV1 responders (CFB ≥ 100 ml), rescue medication use and safety were evaluated.ResultsThe MN population comprised 63% of the intent-to-treat (ITT) population (148/236 patients) and had similar baseline demographics. At week 8, adjusted mean (standard error) improvements in trough FEV1 from baseline were clinically meaningful for both combinations (UMEC/VI: 167 [17] ml; TIO/OLO 110 [18] ml; adjusted mean difference [95% confidence interval (CI)]: 57 [23–92] ml; p = 0.001; %CFB: 11 vs. 8%). Proportion of FEV1 responders was greater with UMEC/VI versus TIO/OLO at week 8 (60 vs. 42%; odds ratio [95% CI] 1.90 [1.12–3.22]; p = 0.018). Reduction in rescue medication use was 0.20 (95% CI 0.07–0.34) puffs/day greater with UMEC/VI versus TIO/OLO over weeks 1–8 (p = 0.003). Adverse events incidence was similar (UMEC/VI: 24%; TIO/OLO: 29%).ConclusionsThese results highlight that the efficacy difference between UMEC/VI and TIO/OLO demonstrated in the ITT population is maintained in MN patients. Greater lung function improvements with UMEC/VI versus TIO/OLO were accompanied by symptom improvements, as reflected in a significantly lower need for supplemental rescue medication.FundingGSK.Trial registrationNCT02799784

Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD

BackgroundThe benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid–LABA or LAMA–LABA), are uncertain.MethodsIn this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate–vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium–vilanterol (at doses of 62.5 μg and 25 μg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.ResultsThe rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate–vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium–vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium–vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium–vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium–vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).ConclusionsTriple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate–vilanterol or umeclidinium–vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium–vilanterol. (Funded by GlaxoSmithKline; IMPACT ClinicalTrials.gov number, NCT02164513.)

Rates of escalation to triple COPD therapy among incident users of LAMA and LAMA/LABA.

Improved outcomes have been reported for patients with chronic obstructive pulmonary disease (COPD) receiving combination long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) therapy compared with LAMA monotherapy. However, little is known about the relative characteristics of these patients and their rates of escalation to triple therapy (TT, combining a LAMA, LABA, and inhaled corticosteroid). This study aimed to characterize patients initiating treatment with the LAMA tiotropium (TIO) and the fixed-dose LAMA/LABA combination therapy umeclidinium/vilanterol (UMEC/VI), and to compare rates of escalation to TT between patients receiving these therapies. Retrospective study of patients with COPD enrolled in a US health insurance plan during 2013-2015 and newly initiated on TIO or UMEC/VI. Patients were ≥40 years of age at index (date of therapy initiation) with continuous enrollment for 12 months pre-index and ≥30 days post-index. LAMA users were propensity score matched 1:1 to LAMA/LABA users, with TT initiation rates reported by cohort using pharmacy claims. 35,357 patients initiating on TIO and 2407 patients initiating on UMEC/VI were identified. After propensity score matching, the rate of TT initiation was significantly higher in new TIO users (n = 1320) than in new UMEC/VI users (n = 1320) (0.92 vs 0.49 per 100 months of exposure, respectively; p < 0.001). Relative to the UMEC/VI cohort, the TIO cohort had an 87% higher risk of TT initiation (hazard ratio: 1.87; 95% confidence interval: 1.4-2.5; p = 0.001). Patients receiving UMEC/VI progressed to TT more slowly, and were at lower risk of progressing to TT, than patients receiving TIO.

Effects of umeclidinium/vilanterol on exercise endurance in COPD: a randomised study.

This multicentre, randomised, double-blind, placebo-controlled, two-period crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) using the endurance shuttle walk test (ESWT).Patients were randomised 1:1 to one of two treatment sequences: 1) UMEC/VI 62.5/25 µg followed by placebo or 2) placebo followed by UMEC/VI 62.5/25 µg. Each treatment was taken once daily for 12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET) at week 12. Secondary end-points included trough forced expiratory volume in 1 s (FEV1) and 3-h post-dose functional residual capacity (FRC), both at week 12. COPD Assessment Test (CAT) score at week 12 was also assessed.UMEC/VI treatment did not result in a statistically significant improvement in EET change from baseline at week 12 versus placebo (p=0.790). However, improvements were observed in trough FEV1 (206 mL, 95% CI 167–246), 3-h post-dose FRC (−346 mL, 95% CI −487 to −204) and CAT score (−1.07 units, 95% CI −2.09 to −0.05) versus placebo at week 12.UMEC/VI did not result in improvements in EET at week 12 versus placebo, despite improvements in measures of lung function, hyperinflation and health status.

Effectiveness of Umeclidinium-Vilanterol for Protocolized Management of Chronic Obstructive Pulmonary Disease Exacerbation in Hospitalized Patients: A Sequential Period Analysis.

Background: Bronchodilator therapy is a foundation of chronic obstructive pulmonary disease (COPD) exacerbation treatment. Although international guidelines recommend short-acting formulations given multiple times per day, long-acting formulations have not been adequately evaluated. The objective of our study was to determine the effectiveness of umeclidinium-vilanterol (UME/VIL), long-acting beta2-agonist/long-acting muscarinic antagonist (LABA/LAMA) as a once-daily alternative for treating COPD exacerbations in hospitalized patients. Methods: In this retrospective sequential period analysis, we reviewed electronic medical records of patients hospitalized for COPD exacerbations before (September 1, 2015 to February 29, 2016) and after (April 1, 2016 to September 30, 2016) incorporation of UME/VIL into our standard COPD protocol. Before implementation, patients received a daily anticholinergic plus twice-daily long-acting beta2-agonist therapy (tiotropium plus formoterol, n=65). After implementation, UME/VIL replaced the previous regimen (n=58). No other changes were made to the COPD protocol. The primary outcome was 30-day hospital readmission rate. Hospital length of stay, 30-day mortality, and cost of care were analyzed as secondary outcomes. Results: A trend toward increased 30-day readmission rates in the post-intervention group (24.1% versus 10.8%, p=0.049) was no longer statistically significant after adjustment for severity of illness (based on case-mix index) and complications or comorbidities based on diagnosis-related group codes (adjusted odds ratio: 2.499; 95% confidence interval: 0.916-7.380; p=0.074). Conclusion: After adjustment for potential confounders,the implementation of a LABA/LAMA combination product was not statistically associated with an increased 30-day readmission rate but was associated with lower cost of care.

Sensory-mechanical effects of a dual bronchodilator and its anticholinergic component in COPD

This randomized, double-blind, crossover study examined the physiological rationale for using a dual long-acting bronchodilator (umeclidinium/vilanterol (UME/VIL)) versus its muscarinic-antagonist component (UME) as treatment for dyspnea and exercise intolerance in moderate COPD. After each 4-week treatment period, subjects performed pulmonary function and symptom-limited constant-work rate cycling tests with diaphragm electromyogram (EMGdi), esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure measurements. Fourteen subjects completed the study. Both treatments improved spirometry and airway resistance. UME/VIL had larger increases in FEV1 (+0.14±0.23L, p<0.05) but no added reduction in lung hyperinflation compared with UME. Isotime during exercise after UME/VIL versus UME (p<0.05): “unpleasantness of breathing” fell 0.8±1.3 Borg units; mean expiratory flow and ventilation increased; Pdi and Pga decreased. There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi) or respiratory muscle effort (Pes swings) during exercise. UME/VIL compared with UME was associated with reduced breathing unpleasantness reflecting improved airway and respiratory muscle function during exercise.

Dual bronchodilation in COPD: lung function and patient-reported outcomes - a review.

Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol–glycopyrronium once daily, eight for umeclidinium–vilanterol once daily, three for tiotropium–olodaterol once daily, and two for aclidinium–formoterol twice daily). Results from these studies demonstrated that the LAMA–LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA–LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety profiles of the FDCs were similar to placebo. Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA–LAMA combinations.

Prevention of clinically important deteriorations in COPD with umeclidinium/vilanterol.

BackgroundMinimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis. We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD. The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.MethodsThis study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations. Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.ResultsIn Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%). The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001). In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%). UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).ConclusionThis exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods. UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy.

New combination bronchodilators for chronic obstructive pulmonary disease: current evidence and future perspectives.

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80–90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.

Anoro Ellipta: dry powder LAMA/LABA combination for COPD

Anoro Ellipta is the first inhaler to combine a LAMA and a LABA in a single unit. Here we present the clinical data relating to its efficacy and adverse events and look at its place in the management of COPD.

Diagnosis and pharmacotherapy of stable chronic obstructive pulmonary disease: the finnish guidelines.

The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD). The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD. This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD. It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers. The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations. The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient. The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma–COPD overlap syndrome (ACOS). These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions. For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol–ipratropium) is recommended in patients with less symptoms. If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended. For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide–formoterol, beclomethasone dipropionate–formoterol, fluticasone propionate–salmeterol or fluticasone furoate–vilanterol) is recommended as a first choice. Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium–indacaterol or umeclidinium–vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic. If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast. ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD. Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD. Thus, evidence-based recommendation of treatment cannot be given. The treatment should cover both diseases. Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both).

Current optimization of combined therapy for chronic obstructive pulmonary disease

Testing the new combined bronchodilator Anoro Ellipta in different clinical trials gives to its high clinical efficacy and safety in chronic obstructive pulmonary disease. The drug contains the molecules of sustained-release selective β2-adrenergic receptor agonist (vilanterol) and a muscarinic cholinergic receptor antagonist (umeclidinium bromide). The bronchodilating mechanisms of umeclidinium bromide are in the competitive inhibition of the binding of acetylcholine with muscarinic acetylcholine receptors of airway smooth muscles whereas in those of vilanterol are in that with the stimulation of intracellular adenylate cyclase. On days 1 and 24 after inhalation of the first dose of vilanterol and umeclidinium bromide, there was a significant increase in the forced expiratory volume in one second as compared to placebo. No clinical effects on QT interval on an electrocardiogram and cardiac rhythm were found. The benefits of an inhalation device (Ellipta) are its innovation design ensuring the effective delivery of an aerosol dose into the airway, convenience, and simplicity.

PRS45 - Cost Effectiveness of Umeclidinium/Vilanterol (UMEC/VI) Combination Therapy Among Symptomatic COPD Patients

PRS45 - Cost Effectiveness of Umeclidinium/Vilanterol (UMEC/VI) Combination Therapy Among Symptomatic COPD Patients

Efficacy and Safety of Umeclidinium/Vilanterol (UMEC/VI) Once Daily (OD) vs Fluticasone/Salmeterol Combination (FSC) Twice Daily (BD) in Patients With Moderate-to-Severe COPD and Infrequent COPD Exacerbations

Efficacy and Safety of Umeclidinium/Vilanterol (UMEC/VI) Once Daily (OD) vs Fluticasone/Salmeterol Combination (FSC) Twice Daily (BD) in Patients With Moderate-to-Severe COPD and Infrequent COPD Exacerbations