Clinical Characteristics, Treatment Persistence, and Outcomes Among Patients With COPD Treated With Single- or Multiple-Inhaler Triple Therapy: A Retrospective Analysis in Spain

Abstract

BackgroundCOPD is a leading cause of death and disability. COPD therapy goals include reducing exacerbations and improving symptom control. Single-inhaler triple therapy (SITT) or multiple-inhaler triple therapy (MITT) is indicated for patients with frequent exacerbations despite bronchodilator therapy. No available evidence compares SITT vs MITT in Spain in terms of treatment persistence, exacerbations, and other outcomes.Research QuestionDo COPD patients in Spain initiating SITT vs MITT have improved persistence, exacerbations, and health care resource utilization?Study Design and MethodsThis real-world, observational, retrospective cohort study analyzed electronic health records in the Spanish National Healthcare System BIG-PAC database to identify COPD patients aged ≥ 40 years initiating SITT or MITT (using two or three inhalers) between June 1, 2018 and December 31, 2019. Comparative data on persistence (allowing up to 60 days without prescription refill), exacerbation rates, and health care resource utilization and costs during 12-month follow-up were analyzed. Multivariate adjusted analyses were performed.ResultsEligible patients (N = 4,625) initiating SITT (n = 1,011) or MITT (n = 3,614) had a mean age of 70.9 years; most were male (73.9%) with mainly moderate (62.0%) or severe (26.5%) airflow limitation. Between-cohort baseline characteristics were similar. At 12-month follow-up, SITT patients had higher persistence (hazard ratio [HR] = 1.37; 95% CI = 1.22-1.53; P < .001), reduced risk of exacerbations (HR = 0.68; 95% CI = 0.61-0.77; P = .001), and lower all-cause mortality risk (HR = 0.67; 95% CI = 0.63-0.71, P = .027), compared with MITT patients. SITT was associated with significantly reduced health care resource use (mean annual cost savings: €403 vs MITT). For both SITT and MITT, persistence was associated with improved exacerbation rates vs nonpersistence, and substantial adjusted mean annual cost savings (€2,115 and €2,700, respectively).InterpretationPatients initiating SITT had a clinically relevant improvement in persistence leading to reductions in mortality, incidence of exacerbations, and health care resource use with consequent mean cost savings. COPD is a leading cause of death and disability. COPD therapy goals include reducing exacerbations and improving symptom control. Single-inhaler triple therapy (SITT) or multiple-inhaler triple therapy (MITT) is indicated for patients with frequent exacerbations despite bronchodilator therapy. No available evidence compares SITT vs MITT in Spain in terms of treatment persistence, exacerbations, and other outcomes. Do COPD patients in Spain initiating SITT vs MITT have improved persistence, exacerbations, and health care resource utilization? This real-world, observational, retrospective cohort study analyzed electronic health records in the Spanish National Healthcare System BIG-PAC database to identify COPD patients aged ≥ 40 years initiating SITT or MITT (using two or three inhalers) between June 1, 2018 and December 31, 2019. Comparative data on persistence (allowing up to 60 days without prescription refill), exacerbation rates, and health care resource utilization and costs during 12-month follow-up were analyzed. Multivariate adjusted analyses were performed. Eligible patients (N = 4,625) initiating SITT (n = 1,011) or MITT (n = 3,614) had a mean age of 70.9 years; most were male (73.9%) with mainly moderate (62.0%) or severe (26.5%) airflow limitation. Between-cohort baseline characteristics were similar. At 12-month follow-up, SITT patients had higher persistence (hazard ratio [HR] = 1.37; 95% CI = 1.22-1.53; P < .001), reduced risk of exacerbations (HR = 0.68; 95% CI = 0.61-0.77; P = .001), and lower all-cause mortality risk (HR = 0.67; 95% CI = 0.63-0.71, P = .027), compared with MITT patients. SITT was associated with significantly reduced health care resource use (mean annual cost savings: €403 vs MITT). For both SITT and MITT, persistence was associated with improved exacerbation rates vs nonpersistence, and substantial adjusted mean annual cost savings (€2,115 and €2,700, respectively). Patients initiating SITT had a clinically relevant improvement in persistence leading to reductions in mortality, incidence of exacerbations, and health care resource use with consequent mean cost savings. FOR EDITORIAL COMMENT, SEE PAGE 947 Take-home PointsStudy Question: Do patients with COPD in Spain initiating single-inhaler triple therapy (SITT) vs multiple-inhaler triple therapy (MITT) have improved persistence, exacerbations, and health care resource utilization?Results: At 12-month follow-up, compared with MITT patients, SITT patients had higher persistence, a reduced risk of exacerbations, a lower risk of mortality, and reduced health care resource use with consequent mean cost savings.Interpretation: Patients initiating SITT had a clinically relevant improvement in persistence, leading to reductions in mortality and in the incidence of exacerbations, compared with patients initiating MITT. SITT was associated with significant reductions in health care resource use with consequent cost savings. COPD is the third leading cause of death globally, accounting for 3.23 million deaths in 2019, with more than 80% occurring in low- and middle-income countries.1World Health Organization (WHO)Chronic obstructive pulmonary disease (COPD).https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)Date: 2021Date accessed: September 14, 2021Google Scholar,2GBD Chronic Respiratory Disease CollaboratorsPrevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Respir Med. 2020; 8: 585-596Abstract Full Text Full Text PDF PubMed Scopus (491) Google Scholar In Spain, COPD is the fourth leading cause of death, accounting for nearly 7% of all deaths nationally.3Soriano J.B. Rojas-Rueda D. Alonso J. et al.The burden of disease in Spain: results from the Global Burden of Disease 2016.Med Clin (Barc). 2018; 151: 171-190Crossref PubMed Scopus (78) Google Scholar COPD is characterized by persistent respiratory symptoms such as dyspnea, cough or the production of sputum, and restricted airflow.4Global Initiative for Chronic Obstructive Lung DiseaseGlobal strategy for the diagnosis, management, and prevention of chronic obstructive lung disease.https://goldcopd.org/2021-gold-reports/Date: 2021Date accessed: September 14, 2021Google Scholar A feature of COPD is the appearance of episodes of worsening symptoms—exacerbations that lead to substantial morbidity and mortality.5Hartl S. Lopez-Campos J.L. Pozo-Rodriguez F. et al.Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD audit.Eur Respir J. 2016; 47: 113-121Crossref PubMed Scopus (134) Google Scholar Current Spanish and international COPD guidelines recommend short- and long-acting bronchodilators for symptomatic relief and maintenance of COPD.4Global Initiative for Chronic Obstructive Lung DiseaseGlobal strategy for the diagnosis, management, and prevention of chronic obstructive lung disease.https://goldcopd.org/2021-gold-reports/Date: 2021Date accessed: September 14, 2021Google Scholar,6Miravitlles M. Calle M. Molina J. et al.Spanish COPD Guidelines (GesEPOC) 2021: updated pharmacological treatment of stable COPD.Arch Bronconeumol. 2022; 58: 69-81Crossref PubMed Scopus (50) Google Scholar These include the anticholinergic classes of short-acting muscarinic antagonists and long-acting muscarinic antagonists (LAMA), and short-acting β2-agonists (SABA) and long-acting β2-agonists (LABA). The addition of inhaled corticosteroids (ICS) is indicated for patients with frequent exacerbations despite optimal bronchodilator therapy, particularly in patients with high blood eosinophils.4Global Initiative for Chronic Obstructive Lung DiseaseGlobal strategy for the diagnosis, management, and prevention of chronic obstructive lung disease.https://goldcopd.org/2021-gold-reports/Date: 2021Date accessed: September 14, 2021Google Scholar Data from multiple clinical trials support the use of single-inhaler triple combination therapy compared with dual ICS/LABA7Siler T.M. Kerwin E. Singletary K. Brooks J. Church A. Efficacy and safety of umeclidinium added to fluticasone propionate/salmeterol in patients with COPD: results of two randomized, double-blind studies.COPD. 2016; 13: 1-10Crossref PubMed Scopus (52) Google Scholar, 8Singh 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: 963-973Abstract Full Text Full Text PDF PubMed Scopus (312) Google Scholar, 9Vestbo 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: 1919-1929Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar, 10Lipson D.A. 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: 438-446Crossref PubMed Scopus (223) Google Scholar, 11Lipson D.A. Barnhart F. Brealey N. et al.Once-daily single-inhaler triple versus dual therapy in patients with COPD.N Engl J Med. 2018; 378: 1671-1680Crossref PubMed Scopus (605) Google Scholar, 12Lipson D.A. Crim C. Criner G.J. 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: 1508-1516Crossref PubMed Scopus (83) Google Scholar, 13Rabe K.F. Martinez F.J. Ferguson G.T. et al.Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD.N Engl J Med. 2020; 383: 35-48Crossref PubMed Scopus (173) Google Scholar, 14Ferguson G.T. Rabe K.F. Martinez F.J. 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: 747-758PubMed Scopus (193) Google Scholar or LABA/LAMA therapy.11Lipson D.A. Barnhart F. Brealey N. et al.Once-daily single-inhaler triple versus dual therapy in patients with COPD.N Engl J Med. 2018; 378: 1671-1680Crossref PubMed Scopus (605) Google Scholar, 12Lipson D.A. Crim C. Criner G.J. 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: 1508-1516Crossref PubMed Scopus (83) Google Scholar, 13Rabe K.F. Martinez F.J. Ferguson G.T. et al.Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD.N Engl J Med. 2020; 383: 35-48Crossref PubMed Scopus (173) Google Scholar, 14Ferguson G.T. Rabe K.F. Martinez F.J. 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: 747-758PubMed Scopus (193) Google Scholar, 15Papi 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: 1076-1084Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar Triple combination therapy administered by a single inhaler was effective in reducing the risk of all-cause death and moderate or severe exacerbations compared with single-inhaler dual therapy.12Lipson D.A. Crim C. Criner G.J. 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: 1508-1516Crossref PubMed Scopus (83) Google Scholar,13Rabe K.F. Martinez F.J. Ferguson G.T. et al.Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD.N Engl J Med. 2020; 383: 35-48Crossref PubMed Scopus (173) Google Scholar,16Martinez F.J. Rabe K.F. Ferguson G.T. et al.Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease: a randomized, double-blind, multicenter, parallel-group study.Am J Respir Crit Care Med. 2021; 203: PubMed Scopus (52) Google H. H. Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a of 2021; PubMed Scopus Google Scholar In controlled trials and evidence single-inhaler triple therapy (SITT) was Birk R. Brealey N. et fluticasone furoate/umeclidinium/vilanterol versus fluticasone plus umeclidinium two for chronic obstructive pulmonary disease: a 2018; PubMed Scopus Google G.T. N. C. et al.Once-daily single-inhaler versus multiple-inhaler triple therapy in patients with COPD: lung and health results from two controlled 2020; PubMed Scopus Google Scholar or S. et versus multiple-inhaler triple therapy for COPD in clinical 2021; PubMed Scopus Google Scholar to multiple-inhaler triple therapy administered two with to lung Birk R. Brealey N. et fluticasone furoate/umeclidinium/vilanterol versus fluticasone plus umeclidinium two for chronic obstructive pulmonary disease: a 2018; PubMed Scopus Google Scholar, G.T. N. C. et al.Once-daily single-inhaler versus multiple-inhaler triple therapy in patients with COPD: lung and health results from two controlled 2020; PubMed Scopus Google Scholar, S. et versus multiple-inhaler triple therapy for COPD in clinical 2021; PubMed Scopus Google Scholar and health G.T. N. 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