Vilanterol Research Articles

FLUTICASONE FUROATE AND VILANTEROL (FF/VI) VERSUS FLUTICASONE PROPRIONATE AND FORMOTEROL (FP/FM) AS MAINTENANCE THERAPY IN STABLE ASTHMATIC PATIENTS- A COMPARATIVE STUDY

Background: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). Vilanterol (VI) is a long‐acting beta2‐agonist (LABA) that binds to the beta2‐adrenoceptor on the airway smooth muscle, producing bronchodilation. The corticosteroid fluticasone propionate (FP)and the long-acting β₂-adrenoceptor agonist (LABA) formoterol fumarate (FM) have been combined in a single, pressurized, metered-dose, aerosol inhaler for the maintenance treatment of patients aged ≥12 years with persistent asthma.This study evaluated the efficacy and safety of Fluticasone furoate 100 mcgandVilanterol 6 mcg versus Fluticasone proprionate 250 mcg and Formoterol 25 mcg for 12 weeks in patients with persistent asthma as maintenance therapy. Methods and Materials: A hospital based comparative study was conducted among stable asthmatic patients attended to Santhiram Medical College and General Hospital, Nandyal during January 2024 to June 2024(6months) by using convenient sampling method with sample size 60. Study tool was pre-designed, pre-tested, asthma control questionnaire5 (ACQ5),asthma control test (ACT) and Ask 12 adherence barrier survey. Results: Among 60 patients, 30 patients (Group1) were given Fluticasone furoate and Vilanterol and another 30 patients (Group 2) were given Fluticasone proprionate and Formoterol. All the patients (both the treatment groups) completed the 12 weeks treatment period. Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (376 mL) and FP/FM (353 mL) the adjusted mean treatment difference was not statistically significant. There were no differences between 0- to 4-h serial wmFEV1, asthma control test, ACQ5 and Ask 12 adherence barrier survey. There was no difference in reported exacerbations between treatments. Adverse events reported in the present study were not significant. Both treatments were well tolerated. Conclusion: The present study shows that the efficacy of once daily Fluticasone furoate and Vilanterol was not inferior as compared to the efficacy of twice daily Fluticasone proprionate and Formoterol as maintenance therapy in stable asthmatic patients. Howevertreatment with once daily FF/VI has the advantage of forgetfulness and inconvenience of inhalation.Henceonce daily FF/VI can be also useful for stable asthmatic patients as maintenance therapy as FF/VI DPI treatment.

Comparison of Budesonide/formoterol versus Fluticasone furoate/vilanterol as maintenance and reliever therapy for asthma control: a real-world observational study

BackgroundPrevious studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control.MethodsFrom October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment.ResultsA total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group.ConclusionsIn the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.

Association between Increased Risk of Pneumonia with ICS in COPD: A Continuous Variable Analysis of Patient Factors from the IMPACT Study.

Despite the proven benefits of inhaled corticosteroid (ICS)-containing triple therapy for chronic obstructive pulmonary disease (COPD), clinicians limit patient exposure to ICS due to the risk of pneumonia. However, there are multiple factors associated with the risk of pneumonia in patients with COPD. This posthoc analysis of IMPACT trial data aims to set the risks associated with ICS into a context of specific patient-related factors that contribute to the risk of pneumonia. The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI), FF/VI or UMEC/VI. Annual rate of on-treatment pneumonias in the intent-to-treat population associated with age, body mass index (BMI), percent predicted forced expiratory volume in 1s (FEV1) and blood eosinophil count (BEC) was evaluated. This analysis revealed that the annual rate of pneumonia showed the lowest risk at the age of 50years. The 95% confidence intervals (CI) between ICS-containing and non-ICS containing treatments diverged in ages > 63years, suggesting a significantly increased ICS-related risk in older patients. In contrast, the annual rate of pneumonia rose in both groups below BMI of 22.5kg/m2, but above that, there was no relationship to pneumonia rate and no differential effect between the two groups. The relationship between BEC and pneumonia was flat up to > 300/µL cells with ICS-containing treatment and then rose. In contrast, the rate of pneumonia with non-ICS containing treatment appeared to increase at a lower level of BEC (~ 200/µL). There was little evidence of a differential effect of older age, lower BMI, lower FEV1 and BEC on the pneumonia rate between ICS-containing and non-ICS containing treatments. This analysis points to the need for a balanced approach to risk versus benefit in the use of ICS-containing treatments in COPD. IMPACT ClinicalTrials.gov number, NCT02164513.

Simultaneously determination of fine particle dose of vilanterol and fluticasone furoate for dry powder inhaler (DPI) by utilizing gradient elution in chromatography system

Vilanterol (VT) and fluticasone furoate (FF) are components recently used in dry powder inhaler (DPI) to be administrated for patients with respiratory diseases, such as asthma or chronic obstructive pulmonary disease (COPD). In the present study, an approach to an analytical procedure development and validation is presented. Next generation impactor (NGI) and high performance liquid chromatography (HPLC) with UV detector were applied to determine two compounds and fine particle dose (FPD) of each active ingredients in DPI. The most satisfying chromatographic separation was obtained on Poroshell SB C18 (100 mm × 4.6 mm, 2.7 µm) column applying gradient elution by phosphonate buffer and acetonitrile. VT and FF were detected on a UV detector at wavelength of 210 nm and 245 nm, respectively. Among various coating agents, 4% polyethylene glycol PEG 200 in acetone (w/v) was selected as the most effective. Although various physicochemical properties of VT and FF, the analytical procedure allows simultaneously determine two compounds at different wavelengths. Limit of quantitative (LOQ) of vilanterol and fluticasone furoate were determined as 0.049 µg/ml and 0.032 µg/ml, respectively, what is desirable to determine of FPD of active ingredients in microdoses in DPI. The analytical procedure was determined as linear and accurate in the range of LOQ – 2.5 µg/ml and LOQ – 10.0 µg/ml of VT and FF, respectively. The coefficient of determination (R2) was found to be 0.9999 and 1.000 for VT and FF, respectively.

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach.

Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade2) versus severe and very severe COPD (GOLD grades3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD. The modelling approach used data on decline in forced expiratory volume in 1s (FEV1) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV1 and annual exacerbation rates from age 40 to 75years in COPD with initiation of long-acting anti-muscarinic antagonist(LAMA)/long-acting beta2-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65years of age. Model-predicted decline in FEV1 showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65years preserved an additional 469.7mL or 236.0mL, 327.5mL or 203.3mL, or 213.5mL or 137.5mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65years of age, respectively. This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA.

Real-world effects of once-daily inhaled steroid (fluticasone furoate) combined with long-acting beta-2 agonist (vilanterol) and long-acting muscarinic antagonist (umeclidinium) on lung function tests of asthma patients in Japan.

Background: The Japanese drug use system allowed the once-daily use of inhaled corticosteroid fluticasone furoate (FF) combined with a long-acting beta-2 agonist vilanterol (VI) and a long-acting muscarinic antagonist umeclidinium (UMEC) against asthma on 18 February 2021. We investigated the real-world effects of these drugs (FF/UMEC/VI) mainly on lung function tests. Methods: This was an open-label, uncontrolled, within-group time-series (before-after) study. Prior asthma treatment (inhaled corticosteroid with/without a long-acting beta-2 agonist with/without a long-acting muscarinic antagonist) was switched to FF/UMEC/VI 200/62.5/25μg. Subjects were evaluated by lung function tests prior to, and 1-2months after, initiation of FF/UMEC/VI 200/62.5/25μg. Patients were asked questions regarding the asthma control test and preference for drugs. Results: Overall, 114 asthma outpatients (97% Japanese) were enrolled from February 2021 to April 2022: 104 subjects completed the study. Forced expiratory volume in 1s, peak flow, and asthma control test score of FF/UMEC/VI 200/62.5/25μg-treated subjects were significantly increased (p < 0.001, p < 0.001, and p < 0.01, respectively). In contrast with FF/VI 200/25μg, instantaneous flow at 25% of the forced vital capacity and expiratory reserve volume were significantly increased by FF/UMEC/VI 200/62.5/25μg (p < 0.01, p < 0.05, respectively). Sixty-six percent of subjects declared they wanted to continue FF/UMEC/VI 200/62.5/25μg in the future. Adverse effects, mainly local, were seen in 30% of patients, but no serious adverse effects were seen. Conclusion: Once-daily FF/UMEC/VI 200/62.5/25μg was effective against asthma without serious adverse events. This is the first report that demonstrated FF/UMEC/VI dilated peripheral airways using lung function tests. This evidence on drug effects may improve our understanding of pulmonary physiology and the pathophysiology of asthma.

Mortality Risk and Serious Cardiopulmonary Events in Moderate-to-Severe COPD: Post Hoc Analysis of the IMPACT Trial.

In the InforMing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler fluticasone furoate (FF) /umeclidinium (UMEC) /vilanterol (VI) significantly reduced severe exacerbation rates and all-cause mortality (ACM) risk versus UMEC/VI among patients with chronic obstructive pulmonary disease (COPD). This post hoc analysis aimed to define the risk of ACM during and following a moderate/severe exacerbation, and further determine the benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI using a cardiopulmonary composite adverse event (AE) endpoint. The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25mcg, FF/VI 100/25mcg, or UMEC/VI 62.5/25mcg. Post hoc endpoints included the risk of ACM during, 1-90 and 91-365 days post moderate or severe exacerbation and time-to-first cardiopulmonary composite event. Of the 10,355 patients included, 5034 (49%) experienced moderate/severe exacerbations. Risk of ACM was significantly increased during a severe exacerbation event compared with baseline (hazard ratio [HR]: 41.22 [95% confidence interval (CI) 26.49-64.15]; p<0.001) but not significantly different at 1-90 days post-severe exacerbation (HR: 2.13 [95% CI: 0.86-5.29]; p=0.102). Moderate exacerbations did not significantly increase the risk of ACM during or after an exacerbation. Cardiopulmonary composite events occurred in 647 (16%), 636 (15%), and 356 (17%) patients receiving FF/UMEC/VI, FF/VI, and UMEC/VI, respectively; FF/UMEC/VI significantly reduced cardiopulmonary composite event risk versus UMEC/VI by 16.5% (95% CI: 5.0-26.7; p=0.006). Results confirm a substantial mortality risk during severe exacerbations, and an underlying CV risk. FF/UMEC/VI significantly reduced the risk of a composite cardiopulmonary AE versus UMEC/VI.

Comparison of Clinical Outcomes Among Different Fixed-Dose Combinations of Long-Acting Muscarinic Antagonists and Long-Acting β2-Agonists in Patients With COPD

Researchers have yet to obtain conclusive evidence differentiating among fixed-dose combinations (FDCs) of long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) for COPD in terms of real-world clinical outcomes. What are the differences between available LAMA/LABA FDCs in the risk of acute exacerbation (AE) and cardiovascular events? This retrospective cohort study based on a national insurance claims database included patients with COPD≥ 40 years of age who were newly prescribed glycopyrronium (GLY)/indacaterol (IND), umeclidinium (UMEC)/vilanterol (VI), or tiotropium (TIO)/olodaterol (OLO) FDC between January 1, 2015, and June 30, 2019. Propensity score matching and Cox regression models were used to compare outcomes of AE and cardiovascular events associated with LAMA/LABA FDC treatment. Among the 44,498 patients identified and included, 15,586 received GLY/IND, 20,460 received UMEC/VI, and 8,452 received TIO/OLO. Baseline characteristics were well balanced after 1:1 matching of UMEC/VI and GLY/IND, 2:1 matching of UMEC/VI and TIO/OLO, and 2:1 matching of GLY/IND and TIO/OLO. Risk of severe AE was lower among patients treated with UMEC/VI or GLY/IND than among those who received TIO/OLO (UMEC/VI vsTIO/OLO: 17.85 vs29.32 per 100 person-years; hazard ratio, 0.76; 95%CI, 0.68-0.84; GLY/IND vsTIO/OLO: 15.54 vs25.53 per 100 person-years; hazard ratio, 0.77; 95%CI, 0.67-0.88). In addition, GLY/IND users tended to have a lower risk of cardiovascular events than TIO/OLO users, but the difference dissipated when restricting follow up to a shorter duration. Our results revealed that the risk of severe AE was lower among patients with COPD receiving UMEC/VI or GLY/IND than among those receiving TIO/OLO, whereas the incidence of cardiovascular events was similar across groups but was slightly lower in GLY/IND users when compared with TIO/OLO users. Further research will be required to confirm these findings.

A single inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol for the treatment of COPD

ABSTRACT Introduction Single inhaler triple therapy (SITT) with an inhaled corticosteroid, a long-acting β2-agonist, and a long-acting muscarinic antagonist is an effective and attractive therapeutic option codified in the recommendations of guidelines and treatment strategies for the management of COPD. Areas covered The preclinical and clinical development in COPD of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) SITT and its use in the real world. Expert opinion Findings from phase III/IV trials and the use of FF/UMEC/VI in the real-world setting support the view that it may be a useful, safe, and cost-effective option for the maintenance treatment of COPD, especially when dealing with patients who are not adequately controlled with dual ICS/LABA or LAMA/LABA therapy. Only direct head-to-head comparisons will be able to establish whether FF/UMEC/VI may be preferable to the other SITTs approved for COPD due to its pharmacokinetic and pharmacodynamic characteristics and especially the fact that it is the only one that can be taken once-daily. In addition, there is a need for further studies, especially in the real world, to optimize the positioning of FF/UMEC/VI in the treatment of COPD, also considering the availability of FF/VI and UMEC/VI and the need for better differentiation between the three treatments.

Is single-inhaler triple therapy for COPD cost-effective in the UK? The IMPACT trial.

BackgroundThe IMPACT trial demonstrated superior outcomes following 52 weeks of once-daily single-inhaler treatment with fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) (100/62.5/25 μg) compared with once-daily FF/VI (100/25 μg) or UMEC/VI (62.5/25 μg). This study evaluated the cost-effectiveness of FF/UMEC/VI compared with FF/VI or UMEC/VI for the treatment of chronic obstructive pulmonary disease (COPD) from a UK National Health Service perspective.MethodsPatient characteristics and treatment effects from IMPACT were populated into a hybrid decision tree/Markov economic model. Costs (GB£ inflated to 2018 equivalents) and health outcomes were modelled over a lifetime horizon, with a discount rate of 3.5% per annum applied to both. Sensitivity analyses were performed to test the robustness of key assumptions and input parameters.ResultsCompared with FF/VI and UMEC/VI, FF/UMEC/VI provided an additional 0.296 and 0.145 life years (LYs) (discounted) and 0.275 and 0.118 quality-adjusted life years (QALYs), at an additional cost of £1129 and £760, respectively. Incremental cost-effectiveness ratios (ICERs) for FF/UMEC/VI were £4104/QALY and £3809/LY gained versus FF/VI and £6418/QALY and £5225/LY gained versus UMEC/VI. At a willingness-to-pay threshold of £20 000/QALY, the probability that FF/UMEC/VI was cost-effective was 96% versus FF/VI and 74% versus UMEC/VI. Results were similar in a subgroup of patients recommended triple therapy in the 2019 National Institute for Health and Care Excellence COPD guideline.ConclusionsFF/UMEC/VI single-inhaler triple therapy improved health outcomes and was a cost-effective option compared with FF/VI or UMEC/VI for patients with symptomatic COPD and a history of exacerbations in the UK at recognised cost-effectiveness threshold levels.

Triple therapy in a single inhaler for chronic obstructive pulmonary disease: clinical studies and case report (real practice)

Algorithms for de-escalation of basic therapy, including the abolition of inhaled corticosteroids (ICS), in patients with chronic obstructive pulmonary disease (COPD), as well as the development of clear criteria for prescribing triple therapy in clinical practice remain the subject of numerous studies and discussions. The given case report of managing a patient with a long experience of smoking and severe COPD demonstrated an unsuccessful experience of de-escalation of therapy with the abolition of ICS due to concerns about the fact of pneumonia. The dual bronchodilator therapy prescribed in accordance with modern recommendations was insufficiently effective in preventing exacerbations, and the stabilization of the patient’s condition was observed after the appointment of a fixed triple combination of drugs in a single inhaler (VI/UMEC/FF), which contains vilanterol (VI), umeclidinium bromide (UMEC) and ICS fluticasone furoate (FF). An additional contribution to ensuring clinical success was made by such factors as strict compliance with medical prescriptions by the patient, smoking cessation and compliance with recommendations for maintaining physical activity, compliance with a strict self-isolation regime during the pandemic, which reduced the risks of respiratory viral infections. Additional clinical predictors of the effectiveness of ICS in COPD were the bronchitis type, the persistence of symptoms and the recurrence of exacerbations of the disease after discontinuation of the drug, the level of blood eosinophilia. When deciding whether to prescribe or cancel triple therapy, it is recommended to take into account the data on the effect of ICS on improving the functional parameters and clinical course of the disease with a decrease in symptoms, on reducing the risk of exacerbations, on increasing patient survival and a positive prognosis during COPD.

Effect of Age on Efficacy and Safety of Fluticasone Furoate/Vilanterol (FF/VI), Umeclidinium (UMEC), and UMEC + FF/VI in Patients with Chronic Obstructive Pulmonary Disease: Analyses of Five Randomized Clinical Trials.

IntroductionConcerns have been raised about the practical use and clinical benefits of medications and inhalers in older patients with chronic obstructive pulmonary disease (COPD). Here, we report analyses according to age from five clinical trials evaluating medications administered using the ELLIPTA dry-powder inhaler (DPI).MethodsEfficacy and safety according to age groups (<65 and ≥65 years) were assessed using data from five clinical trials in patients ≥40 years of age with symptomatic COPD. There was a mix of pre-specified and post hoc analyses of two 24-week trials with fluticasone furoate (FF)/vilanterol (VI) 100/25 µg; one 24-week trial with umeclidinium (UMEC) 62.5 µg; and two 12-week trials with UMEC 62.5 µg + FF/VI 100/25 µg. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) obtained 23 and 24 hours after dosing on the last day of the study.ResultsA total of 2876 patients <65 years of age and 2148 patients ≥65 years of age were enrolled across all studies of whom 1333 and 1111 patients, respectively, received treatment at the doses presented. Statistically significant and clinically meaningful treatment differences in improvement from baseline in mean trough FEV1 were reported for active comparators versus placebo at study end for both <65 and ≥65 years subgroups (FF/VI vs placebo: 143 mL and 111 mL; UMEC vs placebo: 110 mL and 123 mL; UMEC + FF/VI vs placebo + FF/VI: 136 mL and 105 mL; p<0.001 for all comparisons). The incidence of adverse events reported for active treatments was similar between age groups.ConclusionThese data provide evidence to support the use of FF/VI, UMEC, or UMEC + FF/VI, all delivered via the ELLIPTA DPI, to treat older (≥65 years) and younger (<65 years) patients with COPD.

INTREPID: single- versus multiple-inhaler triple therapy for COPD in usual clinical practice.

IntroductionReal-world trial data comparing single- with multiple-inhaler triple therapy (MITT) in COPD patients are currently lacking. The effectiveness of once-daily single-inhaler fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) and MITT were compared in usual clinical care.MethodsINTREPID was a multicentre, randomised, open-label, phase IV effectiveness study comparing FF/UMEC/VI 100/62.5/25 µg via the ELLIPTA inhaler with a clinician's choice of any approved non-ELLIPTA MITT in usual COPD clinical practice in five European countries. Primary end-point was proportion of COPD Assessment Test (CAT) responders (≥2-unit decrease in CAT score from baseline) at week 24. Secondary end-points in a subpopulation included change from baseline in forced expiratory volume in 1 s (FEV1) and percentage of patients making at least one critical error in inhalation technique at week 24. Safety was also assessed.Results3092 patients were included (FF/UMEC/VI n=1545; MITT n=1547). The proportion of CAT responders at week 24 was significantly greater with FF/UMEC/VI versus non-ELLIPTA MITT (OR 1.31, 95% CI 1.13–1.51; p<0.001) and mean change from baseline in FEV1 was significantly greater with FF/UMEC/VI (77 mL versus 28 mL; treatment difference 50 mL, 95% CI 26–73 mL; p<0.001). The percentage of patients with at least one critical error in inhalation technique was low in both groups (FF/UMEC/VI 6%; non-ELLIPTA MITT 3%). Safety profiles, including incidence of pneumonia serious adverse events, were similar between treatments.ConclusionsIn a usual clinical care setting, treatment with once-daily single-inhaler FF/UMEC/VI resulted in significantly more patients gaining health status improvement and greater lung function improvement versus non-ELLIPTA MITT.

Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple-Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With COPD: A Post Hoc Analysis of the Informing the Pathway of COPD Treatment Trial

In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vsFF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? IMPACT was a phase III, double-blind, 52-week trial. Patients ≥40 years of age with symptomatic COPD and≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George's Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and1,406 (14%) were≤ 64, 65 to 74, and≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vsFF/VI (%reduction [95%CI]:≤ 64 years, 8%[-1 to 16]; P= .070; 65-74 years, 22%[14-29]; P< .001;≥ 75 years, 18%[3-31]; P= .021) and vsUMEC/VI (≤ 64 years, 16%[7-25]; P= .002; 65-74 years, 33%[25-41]; P< .001;≥ 75 years, 24%[6-38]; P=.012), with greatest rate reduction seen in the 65 to 74 and≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vsFF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855.

Single-Inhaler Triple Therapy and Health-Related Quality of Life in COPD: The IMPACT Study.

IntroductionThe phase 3 InforMing the PAthway of COPD (chronic obstructive pulmonary disease) Treatment (IMPACT) trial, single-inhaler therapy with fluticasone furoate (FF) 100 μg, umeclidinium (UMEC) 62.5 μg, and vilanterol (VI) 25 μg demonstrated a reduction in the rate of moderate or severe exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This article reports additional evidence of improvements in symptoms and health-related quality of life (HRQoL) with FF/UMEC/VI compared with either FF/VI or UMEC/VI from the IMPACT study.MethodsPatient-reported HRQoL assessments and symptom measures included as pre-specified IMPACT end points were the St George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and Baseline Dyspnea Index (BDI) as the anchor for the Transitional Dyspnea Index (TDI) focal score (BDI/TDI) in a subset of patients enrolled at study sites in North America and Europe. Change from baseline was assessed at weeks 4, 28, and 52.ResultsThe intent-to-treat population included 10,355 patients (TDI population: 5058 patients). Clinically meaningful improvements in SGRQ total score between baseline and week 52 favored FF/UMEC/VI over FF/VI (− 1.8 units, p < 0.001) and UMEC/VI (− 1.8 units, p < 0.001). Similar improvements in the CAT and TDI focal score were also observed with FF/UMEC/VI versus FF/VI or UMEC/VI.ConclusionsThis study demonstrates that in patients with symptomatic COPD at risk of exacerbations, once-daily FF/UMEC/VI, compared with FF/VI or UMEC/VI, improves patient-perceived HRQoL and symptoms.Trial Registration NumberNCT02164513.

Adherence and usage patterns of inhaled corticosteroids-long-acting beta-agonists by using inhaler-monitoring technology.

Background: Results of previous research indicate that adherence to prescribed inhaled corticosteroid-long-acting beta2-agonist (ICS-LABA) asthma controller medications is suboptimal, yet actual daily-use patterns are unclear and may be influenced by regimen complexity or dosing frequency. Objective: To investigate real-world use of asthma medications by using inhaler sensors for the ICS-LABA controllers: twice-daily fluticasone propionate (FP) plus salmeterol (SAL) and once-daily fluticasone furoate (FF) plus vilanterol (VI); and albuterol rescue medication. Methods: This longitudinal, two-phase, observational study included adults with asthma-prescribed FP-SAL (phase I) or FF-VI (phase II), and albuterol metered-dose inhalers. The participants completed baseline and follow-up surveys, and used clip-on inhaler sensors to monitor real-time inhaler use over the 6-month study period. Pharmacy claims data for the 6-month follow-up period were used to assess refills of ICS-LABA and albuterol inhalers. Results: Patients who used twice-daily FP-SAL received a sufficient dose (≥2 actuations/day) approximately one third of the time, those on once-daily FF-VI received a sufficient dose (≥1 actuation/day) ∼60% of the time. Patients who used once-daily FF-VI were more likely to take their medication as prescribed versus those who used twice-daily FP-SAL. There were no significant differences in the percentage of albuterol-free days (FP-SAL, 68.06% [n = 241]; FF-VI, 72.67% [n = 127]; p = 0.230). Exploratory outcomes are reported in this article's Online Supplemental Material. Claims-based measures of adherence were higher than sensor-based measures, hence claims data may have overestimated adherence, whereas sensors may have more accurately measured patients' medication use. Conclusion: These data supported the use of inhaler sensors as tools to directly and accurately measure ICS-LABA adherence and rescue medication use, and the adherence benefits of once-daily versus twice-daily ICS-LABA regimens.

COMPARISON BETWEEN UMEC/VI AND FF/VI BASED ON BASELINE FEV1 REVERSIBILITY: SUB-ANALYSIS FROM THE IMPACT TRIAL

COMPARISON BETWEEN UMEC/VI AND FF/VI BASED ON BASELINE FEV1 REVERSIBILITY: SUB-ANALYSIS FROM THE IMPACT TRIAL

COMPARISON BETWEEN FF/UMEC/VI VS UMEC/VI AND FF/VI AND UMEC/VI VS FF/VI BASED ON BASELINE EXACERBATION HISTORY AND FEV1: SUB-ANALYSIS FROM THE IMPACT TRIAL

COMPARISON BETWEEN FF/UMEC/VI VS UMEC/VI AND FF/VI AND UMEC/VI VS FF/VI BASED ON BASELINE EXACERBATION HISTORY AND FEV1: SUB-ANALYSIS FROM THE IMPACT TRIAL

Once-daily fluticasone furoate/vilanterol combination versus twice-daily budesonide/formoterol combination in the treatment of controlled stable asthma: a randomized crossover trial.

IntroductionFluticasone furoate (FF)/vilanterol (VI) dry powder inhaler (DPI) is the only once-daily maintenance inhaled corticosteroid (ICS)/long-acting β2 adrenergic agonist (LABA) combination for asthma. We aimed to compare the clinical effects of once-daily FF/VI and twice-daily budesonide (BUD)/formoterol (FM) DPI in patients with controlled stable asthma.MethodsWe performed a randomized crossover trial in which stable asthmatic patients controlled on ICS/LABA received 8 weeks of FF/VI (100/25 μg 1 puff once-daily) or BUD/FM (160/4.5 μg 2 puffs twice-daily) DPI treatment. After a 4–8-week washout period, patients received another crossover treatment for 8 weeks. We assessed pulmonary function, the 5-item version asthma control questionnaire (ACQ5), the asthma control test (ACT), and fractional exhaled nitric oxide (FeNO) at baseline and after 8 weeks of treatment (week 8). As the primary outcome was change in force expiratory volume in 1 s (FEV1) between baseline and week 8, we evaluated the incidence of asthma exacerbation and adherence barrier questionnaire (Ask-12) at week 8.ResultsTwenty-three patients were initially enrolled in this study; however, one patient had to be excluded. The FF/VI DPI treatment group showed a similar magnitude of change in FEV1 between baseline and week 8 as the BUD/FM DPI treatment group. In addition, there were no significant differences in pulmonary function tests, ACQ5 scores, ACT scores, and FeNO between baseline and week 8 in both groups. Although the incidence of exacerbation did not differ between groups, the Ask-12 score in the FF/VI DPI group was significantly lower than that in the BUD/FM DPI group.ConclusionsThe present study indicates that once-daily FF/VI DPI is not inferior to twice-daily BUD/FM DPI in clinical effect and more likely to improve inconvenience and forgetfulness in inhalation adherence barriers for stable asthma control therapy. Once-daily FF/VI DPI may be an effective alternative for asthma maintenance treatment.

Fluticasone furoate/vilanterol versus fluticasone propionate in patients with asthma and exercise-induced bronchoconstriction

Objective: To investigate whether once-daily (OD) fluticasone furoate (FF)/vilanterol (VI) provides greater long-term protection from postexercise fall in forced expiratory volume in 1 s (FEV1) than twice-daily (BD) fluticasone propionate (FP) in patients with asthma and exercise-induced bronchoconstriction. Methods: A randomized, double-blind, crossover study was conducted in patients (aged 12–50 years) on low-/mid-dose maintenance inhaled corticosteroid. Following a 4-week run-in period (FP 250 µg BD), patients with a ≥ 20% decrease in postexercise FEV1 received FF/VI 100/25 µg OD or FP 250 µg BD for 2 weeks. Exercise challenges were carried out 23 h after the first dose of study medication, and 12 and 23 h after evening clinic dose at the end of the 2-week treatment period. After a 2-week washout period (FP 250 µg), patients crossed over treatments, with procedures and tests repeated. The primary endpoint was mean maximal percentage decrease from pre-exercise FEV1 following exercise challenge 12-h postevening dose on Day 14. Results: The mean maximal percentage decrease from pre-exercise FEV1 after the 12-h exercise challenge (Day 14) was 15.02% with FF/VI, and 16.71% with FP (difference, −1.69; 95% confidence interval, −3.76 to 0.39; p = 0.109). After the 23-h exercise challenge (Day 14), respective mean maximal decreases were 11.90% and 14.05% (difference, −2.15; 95% confidence interval, −4.31 to 0.01). Conclusion: The study failed to show a difference between FF/VI and FP at providing long-term protection from exercise-induced bronchoconstriction.