Benefit/Risk Profile of Single-Inhaler Triple Therapy in COPD

References

• World Health Organization. Health statistics and information systems: projections of mortality and causes of death, 2016 to 2060; 2016. Available from: https://www.who.int/healthinfo/global_burden_disease/projections/en/. Accessed February 11, 2021.
   Google Scholar
• Fletcher MJ, Upton J, Taylor-Fishwick J, et al. COPD uncovered: an international survey on the impact of chronic obstructive pulmonary disease [COPD] on a working age population. BMC Public Health. 2011;11(1):612. doi:10.1186/1471-2458-11-612
   PubMed Web of Science ®Google Scholar
• Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2020 Report. 2020; Available from: https://goldcopd.org/. Accessed February 11, 2021.
   Google Scholar
• Guarascio AJ, Ray SM, Finch CK, Self TH. The clinical and economic burden of chronic obstructive pulmonary disease in the USA.. Clinicoecon Outcomes Res. 2013;5:235–245. doi:10.2147/CEOR.S34321
   PubMedGoogle Scholar
• Miller JD, Foster T, Boulanger L, et al. Direct costs of COPD in the U.S.: an analysis of Medical Expenditure Panel Survey (MEPS) data. COPD. 2005;2(3):311–318.
   PubMedGoogle Scholar
• Miravitlles M, Murio C, Guerrero T, Gisbert R. EPOC DSGDsAyFel. Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Chest. 2002;121(5):1449–1455.
   PubMed Web of Science ®Google Scholar
• Strassels SA, Smith DH, Sullivan SD, Mahajan PS. The costs of treating COPD in the United States. Chest. 2001;119(2):344–352.
   PubMed Web of Science ®Google Scholar
• Anees UR, Ahmad Hassali MA, Muhammad SA, et al. The economic burden of chronic obstructive pulmonary disease (COPD) in the USA, Europe, and Asia: results from a systematic review of the literature. Expert Rev Pharmacoecon Outcomes Res. 2019:1–12.
   PubMed Web of Science ®Google Scholar
• Chenna PR, Mannino DM. Outcomes of severe COPD exacerbations requiring hospitalization. Semin Respir Crit Care Med. 2010;31(3):286–294.
   PubMed Web of Science ®Google Scholar
• Halpin DM, Decramer M, Celli C, Kesten S, Liu L, Tashkin DP. Exacerbation frequency and course of COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:653–661. doi:10.2147/COPD.S34186
   PubMed Web of Science ®Google Scholar
• Halpin DM, Miravitlles M, Metzdorf N, Celli B. Impact and prevention of severe exacerbations of COPD: a review of the evidence. Int J Chron Obstruct Pulmon Dis. 2017;12:2891–2908. doi:10.2147/COPD.S139470
   PubMed Web of Science ®Google Scholar
• Brusselle G, Price D, Gruffydd-Jones K, et al. The inevitable drift to triple therapy in COPD: an analysis of prescribing pathways in the UK.. Int J Chron Obstruct Pulmon Dis. 2015;10:2207–2217. doi:10.2147/COPD.S91694
   PubMed Web of Science ®Google Scholar
• Chalmers JD, Tebboth A, Gayle A, Ternouth A, Ramscar N. Determinants of initial inhaled corticosteroid use in patients with GOLD A/B COPD: a retrospective study of UK general practice. NPJ Prim Care Respir Med. 2017;27(1):43. doi:10.1038/s41533-017-0040-z
   PubMed Web of Science ®Google Scholar
• Fitch K, Iwasaki K, Pyenson B, Plauschinat C, Zhang J. Variation in adherence with Global Initiative for Chronic Obstructive Lung Disease (GOLD) drug therapy guidelines: a retrospective actuarial claims data analysis. Curr Med Res Opin. 2011;27(7):1425–1429. doi:10.1185/03007995.2011.583230
   PubMed Web of Science ®Google Scholar
• Gruffydd-Jones K, Brusselle G, Jones R, et al. Changes in initial COPD treatment choice over time and factors influencing prescribing decisions in UK primary care: a real-world study. NPJ Prim Care Respir Med. 2016;26(1):16002. doi:10.1038/npjpcrm.2016.2
   PubMed Web of Science ®Google Scholar
• Hurst JR, Dilleen M, Morris K, Hills S, Emir B, Jones R. Factors influencing treatment escalation from long-acting muscarinic antagonist monotherapy to triple therapy in patients with COPD: a retrospective THIN-database analysis. Int J Chron Obstruct Pulmon Dis. 2018;13:781–792. doi:10.2147/COPD.S153655
   PubMed Web of Science ®Google Scholar
• Price D, West D, Brusselle G, et al. Management of COPD in the UK primary-care setting: an analysis of real-life prescribing patterns. Int J Chron Obstruct Pulmon Dis. 2014;9:889–904. doi:10.2147/COPD.S62750
   PubMed Web of Science ®Google Scholar
• Halpin DMG, de Jong HJI, Carter V, Skinner D, Price D. Distribution, Temporal Stability and Appropriateness of Therapy of Patients with COPD in the UK in Relation to GOLD 2019. EClinicalMedicine. 2019;14:32–41. doi:10.1016/j.eclinm.2019.07.003
   Google Scholar
• Han MK, Martinez CH, Au DH, et al. Meeting the challenge of COPD care delivery in the USA: a multiprovider perspective. Lancet Respir Med. 2016;4(6):473–526.
   PubMed Web of Science ®Google Scholar
• Ferguson GT, Rabe KF, Martinez FJ, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, Phase 3 randomised controlled trial. Lancet Respir Med. 2018;6(10):747–758.
   PubMed Web of Science ®Google Scholar
• Lipson DA, Barnacle H, Birk R, et al. fulfil trial: once-daily triple therapy for patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;196(4):438–446. doi:10.1164/rccm.201703-0449OC
   PubMed Web of Science ®Google Scholar
• Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671–1680. doi:10.1056/NEJMoa1713901
   PubMed Web of Science ®Google Scholar
• Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018;391(10125):1076–1084. doi:10.1016/S0140-6736(18)30206-X
   PubMed Web of Science ®Google Scholar
• Rabe KF, Martinez FJ, Ferguson GT, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020;383(1):35–48. doi:10.1056/NEJMoa1916046
   PubMed Web of Science ®Google Scholar
• Singh D, Papi A, Corradi M, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016;388(10048):963–973. doi:10.1016/S0140-6736(16)31354-X
   PubMed Web of Science ®Google Scholar
• Vestbo J, Fabbri L, Papi A, et al. Inhaled corticosteroid containing combinations and mortality in COPD. Eur Respir J. 2018;52(6):6. doi:10.1183/13993003.01230-2018
   Web of Science ®Google Scholar
• Agusti A, Fabbri LM, Singh D, et al. Inhaled corticosteroids in COPD: friend or foe? Eur Respir J. 2018;52(6):6. doi:10.1183/13993003.01219-2018
   Web of Science ®Google Scholar
• Lipworth B, Kuo CR, Jabbal S. Current appraisal of single inhaler triple therapy in COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:3003–3009. doi:10.2147/COPD.S177333
   PubMed Web of Science ®Google Scholar
• Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018;13:3971–3981. doi:10.2147/COPD.S185975
   PubMed Web of Science ®Google Scholar
• Mammen MJ, Lloyd DR, Kumar S, et al. Triple therapy versus dual or monotherapy with long-acting bronchodilators for chronic obstructive pulmonary disease. a systematic review and meta-analysis. Ann Am Thorac Soc. 2020;17(10):1308–1318. doi:10.1513/AnnalsATS.202001-023OC
   PubMed Web of Science ®Google Scholar
• Hartley BF, Barnes NC, Lettis S, Compton CH, Papi A, Jones P. Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis. Respir Res. 2020;21(1):5. doi:10.1186/s12931-019-1262-0
   PubMed Web of Science ®Google Scholar
• Han MK, Criner GJ, Dransfield MT, et al. The effect of inhaled corticosteroid withdrawal and baseline inhaled treatment on exacerbations in the impact study. a randomized, double-blind, multicenter clinical trial. Am J Respir Crit Care Med. 2020;202(9):1237–1243. doi:10.1164/rccm.201912-2478OC
   PubMed Web of Science ®Google Scholar
• European Medicines Agency (EMA). Pharmacovigilance Risk Assessment Committee (PRAC), recommendation 2016. Inhaled corticosteroids (ICS) containing medicinal products indicated in the treatment of chronic obstructive pulmonary disease (COPD). 2016; Available from: https://www.ema.europa.eu/medicines/human/referrals/inhaled-corticosteroids-containing-medicinal-products-indicated-treatment-chronic-obstructive. Accessed February 11, 2021.
   Google Scholar
• European Medicines Agency (EMA). Committee for Medicinal Products for Human Use (CHMP), Assessment Report 2018. Trimbow International non-proprietary name: beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium. Procedure No. EMEA/H/C/004257/II/0002. 2018; Available from: https://www.ema.europa.eu/en/documents/variation-report/trimbow-h-c-4257-ii-0002-epar-assessment-report-variation_en.pdf. Accessed February 11, 2021.
   Google Scholar
• EU Clinical Trials Register. A multinational, multicentre, randomised, open-label, active-controlled, 26-week, 2-arm, parallel group study to evaluate the non-inferiority of fixed combination of beclometasone dipropionate plus formoterol fumarate plus glycopyrronium bromide administered via pMDI (CHF 5993) versus fixed combination of fluticasone furoate plus vilanterol administered via DPI (Relvar®) plus tiotropium bromide (Spiriva®) for the treatment of patients with chronic obstructive pulmonary disease. EudraCT number 2014-001487-35. 2018; Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001487-35/results. Accessed February 11, 2021.
   Google Scholar
• Gershon AS, Guan J, Victor JC, Goldstein R, To T. Quantifying health services use for chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(6):596–601. doi:10.1164/rccm.201211-2044OC
   PubMed Web of Science ®Google Scholar
• Johannesdottir SA, Christiansen CF, Johansen MB, et al. Hospitalization with acute exacerbation of chronic obstructive pulmonary disease and associated health resource utilization: a population-based Danish cohort study. J Med Econ. 2013;16(7):897–906. doi:10.3111/13696998.2013.800525
   PubMedGoogle Scholar
• Soler-Cataluna JJ. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(11):925–931. doi:10.1136/thx.2005.040527
   PubMed Web of Science ®Google Scholar
• Soler-Cataluna JJ, Martinez-Garcia MÁ, Sanchez LS, Tordera MP, Sanchez PR. Severe exacerbations and BODE index: two independent risk factors for death in male COPD patients. Respir Med. 2009;103(5):692–699. doi:10.1016/j.rmed.2008.12.005
   PubMed Web of Science ®Google Scholar
• Rothnie KJ, Mullerova H, Smeeth L, Quint JK. Natural history of chronic obstructive pulmonary disease exacerbations in a general practice–based population with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;198(4):464–471. doi:10.1164/rccm.201710-2029OC
   PubMed Web of Science ®Google Scholar
• Calverley PMA, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2017;196(4):775–789. doi:10.1056/NEJMoa063070
   Web of Science ®Google Scholar
• Vestbo J, Anderson JA, Brook RD, et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet. 2016;387(10030):1817–1826.
   PubMed Web of Science ®Google Scholar
• Lipson DA, Crim C, Criner GJ, et al. Reduction in all-cause mortality with fluticasone furoate/umeclidinium/vilanterol in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020;201(12):1508–1516.
   PubMed Web of Science ®Google Scholar
• Randomised trial of cholesterol lowering in. 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–1389.
   PubMed Web of Science ®Google Scholar
• UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854–865.
   PubMed Web of Science ®Google Scholar
• Anthonisen NR, Skeans MA, Wise RA, et al. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med. 2005;142(4):233–239.
   PubMed Web of Science ®Google Scholar
• Yusuf S, Sleight P, et al.; Heart Outcomes Prevention Evaluation Study I. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145–153.
   PubMed Web of Science ®Google Scholar
• Heart Protection Study Collaborative G. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.
   PubMed Web of Science ®Google Scholar
• Williams NP, Coombs NA, Johnson MJ, et al. Seasonality, risk factors and burden of community-acquired pneumonia in COPD patients: a population database study using linked health care records. Int J Chron Obstruct Pulmon Dis. 2017;12:313–322.
   PubMed Web of Science ®Google Scholar
• Vestbo J, Papi A, Corradi M, et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Lancet. 2017;389(10082):1919–1929.
   PubMed Web of Science ®Google Scholar
• Dransfield MT, Bourbeau J, Jones PW, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013;1(3):210–223.
   PubMed Web of Science ®Google Scholar
• Papi A, Dokic D, Tzimas W, et al. Fluticasone propionate/formoterol for COPD management: a randomized controlled trial. Int J Chron Obstruct Pulmon Dis. 2017;12:1961–1971.
   PubMed Web of Science ®Google Scholar
• Sharafkhaneh A, Southard JG, Goldman M, Uryniak T, Martin UJ. Effect of budesonide/formoterol pMDI on COPD exacerbations: a double-blind, randomized study. Respir Med. 2012;106(2):257–268.
   PubMed Web of Science ®Google Scholar
• Vogelmeier C, Paggiaro PL, Dorca J, et al. Efficacy and safety of aclidinium/formoterol versus salmeterol/fluticasone: a phase 3 COPD study. Eur Respir J. 2016;48(4):1030–1039.
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med. 2016;374(23):2222–2234.
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Calverley PM, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177(1):19–26.
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Singh D, Vestbo J, et al. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014;108(8):1153–1162.
   PubMed Web of Science ®Google Scholar
• Williams NP, Ostridge K, Devaster JM, et al. Impact of radiologically stratified exacerbations: insights into pneumonia aetiology in COPD. Respir Res. 2018;19(1):143.
   PubMed Web of Science ®Google Scholar
• Hurst JR. Consolidation and Exacerbation of COPD. Med Sci. 2018;6:2.
   Google Scholar
• Restrepo MI, Sibila O, Anzueto A. Pneumonia in Patients with Chronic Obstructive Pulmonary Disease. Tuberc Respir Dis. 2018;81(3):187–197.
   PubMed Web of Science ®Google Scholar
• Saleh A, Lopez-Campos JL, Hartl S. The effect of incidental consolidation on management and outcomes in COPD Exacerbations: data from the European COPD Audit. PLoS One. 2015;10(7):e0134004.
   PubMed Web of Science ®Google Scholar
• Dransfield M, Crim C, Criner G, et al. Risk of exacerbation and pneumonia with single inhaler triple therapy versus dual therapy in IMPACT. Eur Respir J. 2018;52(suppl62):PA1991.
   Google Scholar
• Bafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018;6(2):117–126.
   PubMed Web of Science ®Google Scholar
• Pascoe S, Barnes N, Brusselle G, et al. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med. 2019;7(9):745–756.
   PubMed Web of Science ®Google Scholar
• Pascoe S, Pavord I, Hinds D, Locantore N, Barnes N. The association between blood eosinophils and risk and treatment outcome in COPD is not dichotomised. Lancet Respir Med. 2018a;6(5):e18.
   PubMed Web of Science ®Google Scholar
• Bateman ED, Chapman KR, Singh D, et al. Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT). Respir Res. 2015;16:92.
   PubMed Web of Science ®Google Scholar
• Cazzola M, Molimard M. The scientific rationale for combining long-acting beta2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther. 2010;23(4):257–267.
   PubMed Web of Science ®Google Scholar
• Farne HA, Cates CJ. Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015;10:CD008989.
   Google Scholar
• Mahler DA, Decramer M, D’Urzo A, et al. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. Eur Respir J. 2014;43(6):1599–1609.
   PubMed Web of Science ®Google Scholar
• Singh D, Ferguson GT, Bolitschek J, et al. Tiotropium + olodaterol shows clinically meaningful improvements in quality of life. Respir Med. 2015;109(10):1312–1319.
   PubMed Web of Science ®Google Scholar
• van der Molen T, Cazzola M. Beyond lung function in COPD management: effectiveness of LABA/LAMA combination therapy on patient-centred outcomes. Prim Care Respir J. 2012;21(1):101–108.
   PubMedGoogle Scholar
• Wilkie M, Finch S, Schembri S. Inhaled Corticosteroids for chronic obstructive pulmonary disease–the shifting treatment paradigm. COPD. 2015;12(5):582–590.
   PubMedGoogle Scholar
• Bjermer L, Kerwin E, Maltais F, et al. Comparative efficacy and safety of umeclidinium/ vilanterol, umeclidinium and salmeterol in symptomatic maintenance-naïve and maintenance-treated chronic obstructive pulmonary disease: a prospective analysis of the EMAX trial. Am J Respir Crit Care Med. 2019;199:A3317.
   Web of Science ®Google Scholar
• Maltais F, Bjermer L, Kerwin EM, et al. Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial. Respir Res. 2019;20(1):238.
   PubMed Web of Science ®Google Scholar
• Decramer M, Anzueto A, Kerwin E, et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med. 2014;2(6):472–486.
   PubMed Web of Science ®Google Scholar
• Oba Y, Sarva ST, Dias S. Efficacy and safety of long-acting beta-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis. Thorax. 2016;71(1):15–25.
   PubMed Web of Science ®Google Scholar
• Calzetta L, Rogliani P, Matera MG, Cazzola M, Systematic Review A. With meta-analysis of dual bronchodilation with LAMA/LABA for the Treatment of Stable COPD. Chest. 2016;149(5):1181–1196.
   PubMed Web of Science ®Google Scholar
• Maleki-Yazdi MR, Singh D, Anzueto A, Tombs L, Fahy WA, Assessing Short-term NI. Deterioration in maintenance-naive patients with COPD receiving umeclidinium/vilanterol and tiotropium: a pooled analysis of three randomized trials. Adv Ther. 2017;33(12):2188–2199.
   PubMed Web of Science ®Google Scholar
• Singh D, Gaga M, Schmidt O, et al. Effects of tiotropium + olodaterol versus tiotropium or placebo by COPD disease severity and previous treatment history in the OTEMTO(R) studies. Respir Res. 2016;17(1):73.
   PubMedGoogle Scholar
• Gaduzo S, McGovern V, Roberts J, Scullion JE, Singh D. When to use single-inhaler triple therapy in COPD: a practical approach for primary care health care professionals. Int J Chron Obstruct Pulmon Dis. 2019;14:391–401.
   PubMed Web of Science ®Google Scholar
• Perera PN, Armstrong EP, Sherrill DL, Skrepnek GH. Acute exacerbations of COPD in the United States: inpatient burden and predictors of costs and mortality. COPD. 2012;9(2):131–141.
   PubMedGoogle Scholar
• Yu AP, Guerin A. Ponce de Leon D, et al. Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers. J Med Econ. 2011;14(4):486–496.
   PubMedGoogle Scholar
• Zhang S, King D, Rosen VM, Ismaila AS. Impact of single combination inhaler versus multiple inhalers to deliver the same medications for patients with asthma or COPD: a systematic literature review. Int J Chron Obstruct Pulmon Dis. 2020;15:417–438.
   PubMed Web of Science ®Google Scholar
• Makela MJ, Backer V, Hedegaard M, Larsson K. Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD. Respir Med. 2013;107(10):1481–1490.
   PubMed Web of Science ®Google Scholar
• Lopez-Campos JL, Quintana Gallego E, Carrasco Hernandez L. Status of and strategies for improving adherence to COPD treatment. Int J Chron Obstruct Pulmon Dis. 2019;14:1503–1515.
   PubMed Web of Science ®Google Scholar
• Halpin DMG, Worsley S, Ismaila AS, et al. INTREPID: clinical effectiveness of once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol versus multiple-inhaler triple therapy in usual clinical practice. Am J Respir Crit Care Med. 2020;201:A4313.
   Web of Science ®Google Scholar
• GlaxoSmithKline. A comparison study between the fixed dose triple combination of fluticasone furoate/umeclidinium/vilanterol trifenatate (FF/UMEC/VI) with budesonide/formoterol in subjects with chronic obstructive pulmonary disease (COPD) – Study 116853 (NCT02345161). Available from: https://www.gsk-studyregister.com/en/trial-details/?id=116853. Accessed February 11, 2021.
   Google Scholar
• Rabe KF, Martinez FJ, Singh D, et al. Improvements in lung function with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) versus dual therapies in patients with COPD: a sub-study of the ETHOS trial. American Thoracic Society - 116th International Conference; 2020.
   Google Scholar
• GlaxoSmithKline. A study comparing the efficacy, safety and tolerability of fixed dose combination (FDC) of FF/UMEC/VI with the FDC of FF/VI and UMEC/VI; administered once-daily via a dry powder inhaler (DPI) in subjects with chronic obstructive pulmonary disease (COPD) – Study 116855 (NCT02164513). Available from: https://www.gsk-studyregister.com/en/trial-details/?id=116855. Accessed February 11, 2021.
   Google Scholar
• Rabe KF, Martinez FJ, Ferguson GT, et al. A Phase III study of triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler 320/18/9.6mug and 160/18/9.6mug using co-suspension delivery technology in moderate-to-very severe COPD: the ETHOS study protocol. Respir Med. 2019;158:59–66.
   PubMed Web of Science ®Google Scholar