Umeclidinium Research Articles

In Vitro Analysis of Aerodynamic Properties and Co-Deposition of a Fixed-Dose Combination of Fluticasone Furoate, Umeclidinium Bromide, and Vilanterol Trifenatate.

Effective airway delivery of a fixed-dose combination of triple-aerosolized inhaled corticosteroid (ICS)/long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) is likely to positively affect therapeutic responses predicted in patients with asthma and chronic obstructive pulmonary disease. This study aimed to conduct in vitro fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide depositions in a Next Generation Impactor. The aerodynamic properties of these inhaled medications influence the spatial distribution and drug abundance, particularly in the smaller airways, to reverse or alleviate disease pathology. The Next Generation Impactor was used to demonstrate the aerodynamic particle size distributions of fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide delivered from a dry powder inhaler at different flow rates across all stages of the impactors. This in vitro study analyzed the distribution pattern of individual drug components to simulate mono-component deposition and co-deposition in the official model in the United States Pharmacopeia. An Andersen cascade impactor together with scanning electron microscope-energy-dispersive X-ray was employed to observe the drug deposition on each stage of the impactor. We found that the distribution pattern of each component at the same cascade level was comparable, and the aerosol particles of the three drugs reached the in vitro representation of the lower airway compartment. The specified flow rates generated the desired fine particle fraction, fine particle dose, and mass median aerodynamic diameter. Our results also demonstrated visualized deposition patterns of the delivered drugs from different stages of the cascade impactor that may predict deposition as it occurs in vivo. Spatial distribution and abundance of ICS/LABA/LAMA in the same cascade levels were closely comparable, and the aerosol particles were able to reach the small aerosol-sized cascades at the lower levels to some extent.

Interaction between fluticasone furoate and umeclidinium in passively sensitized isolated human airways

Asthma management often includes inhaled corticosteroids (ICSs), with additional controllers like long-acting muscarinic antagonists (LAMAs) for severe cases. The primary goal of this study was to investigate the pharmacological interaction between various concentrations of fluticasone furoate (FF) and umeclidinium (UME) in isolated human airways to determine the nature of their interaction, whether synergistic or additive. Medium bronchi and small airways obtained from patients undergoing lobectomy were passively sensitized to mimic asthmatic conditions. The effects of FF and UME, alone and in combination, on airway relaxation were evaluated using histamine-induced contraction and electrical field stimulation. Pharmacological interactions were analyzed using the Bliss Independence theory. Results indicated that FF induced a partial, concentration-dependent relaxation of sensitized airways, while UME induced a larger relaxation in medium bronchi but a weaker effect in small airways. The combination of FF and UME resulted in significantly greater relaxation than either drug alone, demonstrating synergism at high concentrations in medium bronchi but only additive effects in small airways. This study suggests that higher doses of FF might be necessary in a fixed dose combination to achieve optimal synergistic bronchodilation with UME. Future research should focus on clinical trials to confirm these findings and explore the molecular mechanisms underlying these interactions, potentially improving personalized asthma therapy.

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.

The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro

BackgroundAirway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.MethodsWe investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses.ResultsIL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction.ConclusionThis study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.

A Novel RP-HPLC Method for Simultaneous Estimation of Vilanterol Trifenatate, Umeclidinium Bromide and Fluticasone Furoate in Inhalation Dry Powder Formulation.

The dry powder inhalation formulation containing vilanterol trifenatate, umeclidinium bromide and fluticasone furoate intended for the therapy of bronchospasm related to chronic obstructive pulmonary disease and bronchial asthma was selected for the development and validation of a novel, selective, accurate, precise, quick and cost-efficient reversed-phase, high-performance liquid chromatography method. Neither an official monograph nor a single method has yet been published for the simultaneous estimation of these three compounds, which makes this method novel. The stationary phase of an ACE-C18-PFP column (250mm × 4.6mm, 5μ) was used with a mobile phase of 25-mM sodium perchlorate buffer (pH2.5 adjusted with ortho-phosphoric acid) and acetonitrile (40:60% v/v) at a flow rate of 1mL/min to optimize chromatographic variables. The column temperature was kept at 40°C, and detection was at 224nm, which was the isosbestic point of these three drugs. Well-resolved good peak symmetry was obtained for all three molecules by isocratic elution in less than 10min, and the retention times of vilanterol trifenatate, umeclidinium bromide and fluticasone furoate were found to be 3.7, 5.4 and 8.3min, respectively. The proposed method was validated as per ICH Q2 (R1) guidelines, and the calibration curves were linear in concentration ranges of 5-35μg/mL for vilanterol trifenatate, 5-80μg/mL for umeclidinium bromide and 5-150μg/mL for fluticasone furoate, with mean % recoveries of 99-100%. The limits of detection and quantitation are 0.15 and 0.45μg/mL for vilanterol trifenatate, 0.58 and 1.77μg/mL for umeclidinium bromide and 0.32 and 0.96μg/mL for fluticasone furoate, respectively. Hence, the proposed RP-HPLC technique was successfully used to quantify the inhalation formulation containing all three compounds.

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.

Clinic vs Home Spirometry for Monitoring Lung Function in Patients With Asthma

Studies examining agreement between home and clinic spirometry in patients with asthma are limited, with conflicting results. Understanding the strengths and limitations of telehealth and home spirometry is particularly important considering the SARS-CoV-2 pandemic. How well do home and clinic measurements of trough forced expiratory volume in 1 second (FEV1) agree in patients with uncontrolled asthma? This post hoc analysis used trough FEV1 data from the randomised, double-blind, parallel-group Phase IIIA CAPTAIN (205715; NCT02924688) and Phase IIB (205832; NCT03012061) trials in patients with uncontrolled asthma. CAPTAIN evaluated the impact of adding umeclidinium (UMEC) to fluticasone furoate/vilanterol (FF/VI) via a single inhaler; 205832 investigated adding UMEC to FF versus placebo. Trough FEV1 measurements were collected via home spirometry and supervised in-person spirometry in the research clinic. To compare home and clinic spirometry, we examined the time-course analyses of home and clinic trough FEV1, and generated post hoc Bland-Altman plots to assess agreement between home and clinic spirometry. Data from 2436 (CAPTAIN) and 421 (205832) patients were analysed. Treatment-related improvements in FEV1 were observed in both trials using home and clinic spirometry. Improvements measured by home spirometry were of lower magnitude and less consistent than clinic measurements. Bland-Altman plots suggested poor agreement between home and clinic trough FEV1 at baseline and Week 24. This post hoc comparison of home and clinic spirometry is the largest conducted in asthma. Results showed that home spirometry was less consistent than and lacked agreement with clinic spirometry, suggesting that unsupervised home readings are not interchangeable with clinic measurements. However, these findings may only be applicable to home spirometry using the specific device and coaching methods employed in these studies. Post-pandemic, further research to optimise home spirometry use is needed. Clinicaltrials.gov (NCT03012061; NCT02924688).

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.

Efficacy of Combination Therapy in Patients with Stable Coronary Heart Disease with Comorbid Chronic Obstructive Pulmonary Disease

The objective: to analyze the quality of life (QoL) and functional status after combination therapy in patients with stable coronary heart disease (CHD) and comorbid chronic obstructive pulmonary disease (COPD). Materials and methods. The study included 60 men with stable CHD in combination with COPD. The patients were divided into two groups of 30 people, comparable according to the main indicators. Study group (1) received basic treatment with nebivolol, valsartan, eplerenone, acetylsalicylic acid, rosuvastatin for CHD and basic COPD treatment with combination of umeclidinium bromide (a long-acting cholinolytic) and vilanterol (a long-acting beta2-agonist). Patients from Group 2 in addition tj the basic treatment received L-arginine in the form of an infusion of 4.2% 100 ml solution for 10 days, followed by oral administration at a dose of 3 g per day. The duration of treatment was 6 months. Quality of life was evaluated by validated standardized non-specific questionnaire «The 36-Item Short Form Health Survey» (SF-36), a validated specific respiratory questionnaire of St. George’s Hospital – St. George’s Respiratory Questionnaire (SGRQ). The functional state of patients before and after treatment was evaluated by cardiorespiratory test, which included the distance 6-minutes walk test (6MWT) according to the standard method in combination with pulse oximetry (SpO2), calculation of desaturation level (ΔSpO2), recording of electrocardiogram and blood pressure before and after exercise. Results. After the treatment, patients in both groups noted a significant improvement in quality of life across all domains of the SF-36 questionnaire, which includes 36 questions with physical and mental components. Patients from group 2 demonstrated better results of treatment in all indicators of physical functioning, general health and vital activity than patients from group 1. The results of the quality of life evaluation according to the specific respiratory questionnaire SGRQ also showed a significant improvement in patients of both groups. In both groups, the distance of 6MWT significantly increased, the heart rate at rest and after exercise decreased, and the level of desaturation decreased. In group 2, the increase in the distance of 6MWT, the decrease of desaturation level was significantly better than in group 1. Conclusions. Rational combination treatment of patients with stable coronary heart disease (CHD) with comorbid chronic obstructive pulmonary disease (COPD) includes nebivolol, valsartan, eplerenone, acetylsalicylic acid, rosuvastatin and a combination of vilanterol and umeclidinium bromide, contributes to improving the quality of life of patients and their functional status. Addition of L-arginine to the basic combination treatment of patients with CHD and COPD increases the efficacy of therapy and improves cardiohemodynamics. Addition of L-arginine to the treatment complex contributed to the additional improvement of the physical and mental patterns of quality of life and indicators of cardiorespiratory test.

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.

Efficacy of Combination Therapy in Patients with Stable Coronary Heart Disease with Comorbid Chronic Obstructive Pulmonary Disease

The objective: to analyze the quality of life (QoL) and functional status after combination therapy in patients with stable coronary heart disease (CHD) and comorbid chronic obstructive pulmonary disease (COPD). Materials and methods. The study included 60 men with stable CHD in combination with COPD. The patients were divided into two groups of 30 people, comparable according to the main indicators. Study group (1) received basic treatment with nebivolol, valsartan, eplerenone, acetylsalicylic acid, rosuvastatin for CHD and basic COPD treatment with combination of umeclidinium bromide (a long-acting cholinolytic) and vilanterol (a long-acting beta2-agonist). Patients from Group 2 in addition tj the basic treatment received L-arginine in the form of an infusion of 4.2% 100 ml solution for 10 days, followed by oral administration at a dose of 3 g per day. The duration of treatment was 6 months. Quality of life was evaluated by validated standardized non-specific questionnaire «The 36-Item Short Form Health Survey» (SF-36), a validated specific respiratory questionnaire of St. George’s Hospital – St. George’s Respiratory Questionnaire (SGRQ). The functional state of patients before and after treatment was evaluated by cardiorespiratory test, which included the distance 6-minutes walk test (6MWT) according to the standard method in combination with pulse oximetry (SpO2), calculation of desaturation level (ΔSpO2), recording of electrocardiogram and blood pressure before and after exercise. Results. After the treatment, patients in both groups noted a significant improvement in quality of life across all domains of the SF-36 questionnaire, which includes 36 questions with physical and mental components. Patients from group 2 demonstrated better results of treatment in all indicators of physical functioning, general health and vital activity than patients from group 1. The results of the quality of life evaluation according to the specific respiratory questionnaire SGRQ also showed a significant improvement in patients of both groups. In both groups, the distance of 6MWT significantly increased, the heart rate at rest and after exercise decreased, and the level of desaturation decreased. In group 2, the increase in the distance of 6MWT, the decrease of desaturation level was significantly better than in group 1. Conclusions. Rational combination treatment of patients with stable coronary heart disease (CHD) with comorbid chronic obstructive pulmonary disease (COPD) includes nebivolol, valsartan, eplerenone, acetylsalicylic acid, rosuvastatin and a combination of vilanterol and umeclidinium bromide, contributes to improving the quality of life of patients and their functional status. Addition of L-arginine to the basic combination treatment of patients with CHD and COPD increases the efficacy of therapy and improves cardiohemodynamics. Addition of L-arginine to the treatment complex contributed to the additional improvement of the physical and mental patterns of quality of life and indicators of cardiorespiratory test.

The double bronchodilation era: new capabilities in a new drug delivery device

A literature review presents the efficacy and safety of the new glycopyrronium bromide/formoterol fumarate (GP/FF) combination in the treatment of patients with chronic obstructive pulmonary disease according to the PINNACLE 1, 2, 3, 4 studies. There are 4 fixed LAMA/LABA combinations which used in world practice, as well as in Russia: vilanterol + umeclidinium bromide, glycopyrronium bromide + indacaterol, olodaterol + tiotropium bromide and aclidinium bromide + formoterol. The GP/FF combination also approved in Russia, is currently present in Global Initiative for Chronic Obstructive Lung Disease (GOLD). A new method of co-suspension delivery via the Aerosphere inhaler has been developed for this combination. The efficacy and safety in GP/FF MDI compared to its monocomponents and tiotropium bromide were assessed in phase III clinical trials PINNACLE 1, 2, 3, 4. The GP/FF combination showed an improvement in the morning and after 2 hours parameters of FEV1 compared to monocomponents and placebo. Data from PINNACLE studies showed an improvement in the quality of life associated with a decrease in compared with the baseline level of the overall score on the scale of the St. George’s Hospital Respiratory Questionnaire (SGRQ) in 24 weeks against those taking GP/FF in contrast to monocomponents and placebo. The use of GP/FF showed a significant reduction in theuse of salbutamol compared with placebo. A pooled analysis of PINNACLE 1, 2, 4 demonstrated that GP/FF improved lung functionand reduced the risk of COPD exacerbations compared with monocomponents and placebo. According to the results of the analysis, there was also no increase in the number of the most frequently recorded side effects.

The effectiveness of single inhaler triple therapy in patients with bronchial asthma in real clinical practice

Introduction. About 40% of patients with bronchial asthma on dual therapy with inhaled glucocorticosteroids and long-acting β2-agonists do not achieve asthma control.Aim. To evaluate the efficacy of triple therapy (fluticasone furoate, umeclidinium bromide, vilanterol) in a single inhaler in patients with bronchial asthma in real clinical practice.Material and methods. The study included 43 patients with bronchial asthma from municipal outpatients’ clinics in Ekaterinburg and the Sverdlovsk region. The clinical-functional and clinical-economic efficiency of therapy was evaluated for 6 months before and after the appointment of a triple combination (fluticasone furoate, umeclidinium bromide, vilanterol) in a single inhalerResults and discussion. Of the 43 patients, 39 patients were included in the analysis. During 6 months of triple therapy in a single inhaler, the mean ACT value increased from 13 (Q1–Q3: 12–14) to 21 points (Q1–Q3: 20–22) (p &lt; 0.001), the proportion of patients with uncontrolled asthma decreased from 100% initially to 15.4% at 6 months of therapy (p&lt; 0.001). By the 6th month of therapy, all patients refused to take systemic glucocorticosteroids (p = 0.003), there was an increase in FEV1 from 73.0% (Q1–Q2: 70.0–75.0) to 82% (Q1–Q2: 80.0–86.5) (p &lt; 0.001). The number of ambulance calls (from 0.28 ± 0.46 per 1 patient at baseline) and hospitalizations (from 0.67 ± 0.84 per 1 patient at baseline) decreased to 0 (p &gt;&lt; 0.001) after 6 months of treatment with the study drug. Savings in the management of 1 patient for 6 months on a triple therapy in a single inhaler amounted to 10523 rubles, and the prevented economic damage for 39 patients for 6 months of therapy is 410418 rubles. Conclusion. The triple therapy in a single inhaler made it possible to improve asthma control and respiratory function, stop taking systemic glucocorticosteroids, reduce the number of hospitalizations and emergency calls, while reducing direct costs per unit of efficiency.&gt;&lt; 0.001). The number of ambulance calls (from 0.28 ± 0.46 per 1 patient at baseline) and hospitalizations (from 0.67 ± 0.84 per 1 patient at baseline) decreased to 0 (p&lt; 0.001) after 6 months of treatment with the study drug. Savings in the management of 1 patient for 6 months on a triple therapy in a single inhaler amounted to 10523 rubles, and the prevented economic damage for 39 patients for 6 months of therapy is 410418 rubles.Conclusion. The triple therapy in a single inhaler made it possible to improve asthma control and respiratory function, stop taking systemic glucocorticosteroids, reduce the number of hospitalizations and emergency calls, while reducing direct costs per unit of efficiency.

Experience of using a triple fixed combination in the treatment of patients with chronic obstructive pulmonary disease

To evaluate the effectiveness of a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate in the treatment of chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. The study included 46 patients with severe and extremely severe COPD (GOLD 34) with frequent exacerbations. All patients were divided into 2 groups. The 1st group included 22 COPD patients with a content of eosinophils in the peripheral blood of 300 cells/ml, the 2nd group included 24 COPD patients with no signs of eosinophilic inflammation in the peripheral blood. Group 1 patients were recommended therapy with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate at a dose of 22/55/92 mcg 1 time per day, group 2 patients received vilanterol+umeclidinium bromide at a dose of 22/55 mcg 1 time per day. The duration of follow-up was 12 months. After 12 months of treatment with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate, a statistically significant decrease in peripheral blood eosinophilia was noted in patients with COPD with frequent exacerbations and peripheral blood eosinophilia (p=0.001), as well as a decrease in shortness of breath on the MMRs scale (p=0.001) and the frequency of exacerbations in patients with COPD with frequent exacerbations and eosinophilia (p=0.001). The use of a fixed combination of vilanterol/umeclidinium bromide/fluticasone furoate for 12 months allowed to reduce the impact of the disease, improve respiratory function and quality of life in COPD patients with eosinophilia.

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.

Respiratory diseases advocate living with severe asthma

Respiratory diseases advocate living with severe asthma

Stability indicating RP-HPLC method development and validation for the simultaneous estimation of vilantero land umeclidinium bromide in bulk and pharmaceutical dosage forms

Stability indicating RP-HPLC method development and validation for the simultaneous estimation of vilantero land umeclidinium bromide in bulk and pharmaceutical dosage forms

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.

D010 CAPTAIN STUDY: EFFECTS OF BASELINE IGE LEVELS ON TRIPLE THERAPY RESPONSE IN INADEQUATELY CONTROLLED ASTHMA

CAPTAIN showed that adding umeclidinium (UMEC) to fluticasone furoate/vilanterol (FF/VI) improved lung function and symptom control in uncontrolled asthma; treatment response varied by baseline type-2 inflammatory biomarkers. As IgE may also influence treatment response, we evaluated the impact of adding UMEC and/or increasing FF dose in subgroups defined by baseline IgE levels.