The IMPACT Trial: Single Inhaler Triple Therapy fluticasone Furoate/Umeclidinium/Vilanterol Versus Fluticasone Furoate/Vilanterol and Umeclidinium/Vilanterol in Patients with COPD: Analysis According to Smoking Status

Halpin, Dmg; Bardsley, Samuel; Criner, Gerard J.; Han, M.K.; Jones, Christine; Kilbride, Sally; Lomas, David A.; Martínez, Fernando J.; Pascoe, Steven; Singh, Dave; Wise, R.A.; Lipson, D.A.; Lange, Peter

doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3339

Cited by 2 publications

(4 citation statements)

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“…These results suggest that ICS is likely to be driving this benefit, despite the potential blunting effect of smoking on the clinical response to ICS in COPD 13,14 . This is in line with a recent post hoc analysis of IMPACT, which found FF/UMEC/VI improved clinical outcomes versus dual therapy in patients with symptomatic COPD and a history of exacerbations, regardless of smoking status 15 …”

Section: Discussionsupporting

confidence: 83%

“…13,14 This is in line with a recent post hoc analysis of IMPACT, which found FF/UMEC/VI improved clinical outcomes versus dual therapy in patients with symptomatic COPD and a history of exacerbations, regardless of smoking status. 15 While both subgroups had similar exacerbation history, patients in the CMH+ subgroup had numerically higher rates of on-treatment moderate/severe and severe exacerbations during the study compared with the CMHÀ subgroup, with the greatest difference between CMH subgroup seen in the UMEC/VI treatment arm. This observation provides further support that CMH as defined using the SGRQ respiratory items on chronic cough and phlegm may be a predictor for the risk of future exacerbations.…”

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: Post hoc analysis of the IMPACT trial

et al. 2022

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Background and objective Chronic mucus hypersecretion (CMH) is a clinical phenotype of COPD. This exploratory post hoc analysis assessed relationship between CMH status and treatment response in IMPACT. Methods Patients were randomized to once‐daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg, FF/VI 100/25 μg or UMEC/VI 62.5/25 μg and designated CMH+ if they scored 1/2 in St George's Respiratory Questionnaire (SGRQ) questions 1 and 2. Endpoints assessed by baseline CMH status included on‐treatment exacerbation rates, change from baseline in trough forced expiratory volume in 1 second, SGRQ total score, COPD Assessment Test (CAT) score, proportion of SGRQ and CAT responders at Week 52 and safety. Results Of 10,355 patients in the intent‐to‐treat population, 10,250 reported baseline SGRQ data (CMH+: 62% [n = 6383]). FF/UMEC/VI significantly (p < 0.001) reduced on‐treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in CMH+ (rate ratio: 0.87 and 0.72) and CMH− patients (0.82 and 0.80). FF/UMEC/VI significantly (p < 0.05) reduced on‐treatment severe exacerbation rates versus UMEC/VI in CMH+ (0.62) and CMH− (0.74) subgroups. Similar improvements in health status and lung function with FF/UMEC/VI were observed, regardless of CMH status. In CMH+ patients, FF/VI significantly (p < 0.001) reduced on‐treatment moderate/severe and severe exacerbation rates versus UMEC/VI (0.83 and 0.70). Conclusion FF/UMEC/VI had a favourable benefit: risk profile versus dual therapies irrespective of CMH status. The presence of CMH did not influence treatment response or exacerbations, lung function and/or health status. However, CMH did generate differences when dual therapies were compared and the impact of CMH should be considered in future trial design.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 88%

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Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: Post hoc analysis of the IMPACT trial

et al. 2022

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“…The increase (28%) in UMEC CL/F (lower systemic exposure) for subjects with COPD who smoke is unlikely to be of clinical relevance. Indeed, this difference in UMEC CL/F in subjects who smoke was not reflected in findings from the IMPACT trial across a range of endpoints for FF/UMEC/VI and UMEC/VI [14].…”

Section: Discussionmentioning

confidence: 91%

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

Mehta

Farrell²,

Hayes³

et al. 2019

Clin Pharmacokinet

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Background Population pharmacokinetic methods were used to characterize the pharmacokinetics of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) when administered as a fixed-dose combination via a single closed inhaler. Methods Plasma concentration data from three studies were analyzed using non-linear mixed-effects modeling in NONMEM ®. Results The pooled dataset consisted of 2948, 2589, and 3331 FF, UMEC, and VI observations from 714, 622, and 817 patients with COPD, respectively. There were 41%, 13%, and 21% of observations below the quantification limit for FF, UMEC, and VI, respectively. The pharmacokinetics of FF, UMEC, and VI were all adequately described by a two-compartment model with first-order absorption. The following covariates were statistically significant, but none were considered to be clinically relevant. For FF, Japanese heritage and FF/VI treatment on apparent inhaled clearance (CL/F) with FF CL/F 35% lower in patients of Japanese heritage across all treatments and FF CL/F 42% higher in patients with COPD following FF/VI administration. This is in line with the product label. For UMEC, weight, age, and smoking status on CL/F and weight on apparent volume of distribution (V2/F) with every 10% increase in age from 60 years of age leading to approximately a 6% decrease in UMEC CL/F and every 10% increase in weight from 70 kg leading to approximately a 6% increase in UMEC CL/F and approximately an 8% increase in UMEC V2/F. For a subject with COPD who smoked, UMEC CL/F was 28% higher. For VI, weight on CL/F and smoking status on V2/F with an approximately 4% increase in VI CL/F for every 10% increase in weight from 70 kg, and for a subject with COPD who smoked, VI V2/F was 46% higher. The majority of these covariates have been previously identified in historical analyses. None of these effects were clinically relevant in terms of systemic exposures and do not warrant dose adjustment. Conclusions All FF, UMEC, and VI plasma concentrations were well interspersed with historical data and were all adequately described by a two-compartment model with first-order absorption.

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The IMPACT Trial: Single Inhaler Triple Therapy fluticasone Furoate/Umeclidinium/Vilanterol Versus Fluticasone Furoate/Vilanterol and Umeclidinium/Vilanterol in Patients with COPD: Analysis According to Smoking Status

Cited by 2 publications

References 0 publications

Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: Post hoc analysis of the IMPACT trial

Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: Post hoc analysis of the IMPACT trial

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

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