David A Lipson1, Frank Barnhart1, Noushin Brealey1, Jean Brooks1, Gerard J Criner1, Nicola C Day1, Mark T Dransfield1, David M G Halpin1, MeiLan K Han1, C Elaine Jones1, Sally Kilbride1, Peter Lange1, David A Lomas1, Fernando J Martinez1, Dave Singh1, Maggie Tabberer1, Robert A Wise1, Steven J Pascoe1. 1. From GlaxoSmithKline, Collegeville (D.A. Lipson, J.B., S.J.P.), and the Perelman School of Medicine, University of Pennsylvania (D.A. Lipson), and Lewis Katz School of Medicine at Temple University (G.J.C.), Philadelphia - all in Pennsylvania; GlaxoSmithKline, Research Triangle Park, NC (F.B., C.E.J.); GlaxoSmithKline, Stockley Park West, Uxbridge (N.B., N.C.D., S.K., M.T.), the Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter (D.M.G.H.), UCL Respiratory, University College London, London (D.A. Lomas), and the Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust, Manchester (D.S.) - all in the United Kingdom; the Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham (M.T.D.); the Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor (M.K.H.); the Department of Public Health, University of Copenhagen, Copenhagen (P.L.), and the Medical Department, Pulmonary Section, Herlev-Gentofte Hospital, Herlev (P.L.) - both in Denmark; New York-Presbyterian Hospital/Weill Cornell Medical Center, New York (F.J.M.); and the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (R.A.W.).
Abstract
BACKGROUND: The 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. METHODS: In 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. RESULTS: The 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). CONCLUSIONS: Triple 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 .).
RCT Entities:
BACKGROUND: The 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. METHODS: In 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. RESULTS: The 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). CONCLUSIONS: Triple 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 .).
Authors: Wassim W Labaki; Lucas M Kimmig; Gökhan M Mutlu; MeiLan K Han; Surya P Bhatt Journal: Am J Respir Crit Care Med Date: 2019-06-15 Impact factor: 21.405
Authors: Byron Thomashow; James D Crapo; M Bradley Drummond; MeiLan K Han; Ravi Kalhan; Elisha Malanga; Vinny Malanga; David M Mannino; Stephen Rennard; Frank C Sciurba; Kristen S Willard; Robert Wise; Barbara Yawn Journal: Chronic Obstr Pulm Dis Date: 2019-07-24