Abstract
Purpose: This study aimed to compare the efficacy and safety of single inhaler triple
therapy and separate triple therapy in the treatment of patients with moderate to
severe chronic obstructive pulmonary disease (COPD).
Methods: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov
databases were searched, and the search date was set from database inception until
February 15, 2022. Randomized controlled trials of single inhaler triple therapy versus
separate triple therapy, from which the results related to efficacy and safety profiles
were extracted, and the methodologic quality and risk of bias were evaluated.
Findings: Five published articles (6 clinical trials) were screened from 3437 articles
with a total of 4075 patients receiving single inhaler triple therapy and 3533 patients
receiving separate triple therapy. Compared with separate triple therapy, single inhaler
triple therapy significantly increased the change in forced expiratory volume in 1
second from baseline (mean difference = 0.02 L; 95% CI, 0.00-0.05L; P < 0.01), and there was a statistical difference between the 2 groups. No significant
difference was found between the single inhaler triple therapy and separate triple
therapy groups in terms of moderate to severe exacerbation rate (relative risk [RR] = 0.97;
95% CI, 0.85-1.10; P = 0.63), the change in St. George's Respiratory Questionnaire from baseline (mean
difference = 0.34; 95% CI, −0.88 to 1.57; P = 0.58), proportion of St. George's Respiratory Questionnaire responders (RR = 0.99;
95% CI, 0.92-1.06; P = 0.77), adverse events (RR= 1.07; 95% CI, 0.90-1.27; P = 0.42), serious adverse events (RR = 1.02; 95% CI, 0.88-1.18; P = 0.81), mortality (RR = 1.10; 95% CI, 0.65-1.86; P = 0.72), risk of pneumonia (RR = 0.86; 95% CI, 0.62-1.18; P = 0.34), and risk of cardiovascular events (RR = 1.22; 95% CI, 0.91-1.65; P = 0.18).
Implications: Compared with separate triple therapy, single inhaler triple therapy
appears to improve lung function in patients with moderate to severe COPD, especially
in terms of forced expiratory volume in 1 second advantages. Single inhaler triple
therapy may be a feasible and simplified option for patients with moderate to severe
COPD; however, this conclusion needs to be further confirmed by future randomized
controlled trials. (Clin Ther. 2022;XX:XXX–XXX) © 2022 Elsevier HS Journals, Inc.
Key words
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References
- Changes in health in the countries of the UK and 150 English Local Authority areas 199P 2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet. 2018; 392: 1647-1661
- Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019.Eur Respir J. 2019; 531900164
- Single-inhaler triple therapy utilizing the once-daily combination of fluticasone furoate, umeclidinium and vilanterol in the management of COPD: the current evidence base and future prospects.Ther Adv Respir Dis. 2018; 121753466618760779
- Dual combination therapy versus long-acting bronchodilators alone for chronic obstructive pulmonary disease (COPD): a systematic review and network meta-analysis.Cochrane Database Syst Rev. 2018; 12CD012620
- Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary.Am J Respir Crit Care Med. 2017; 195: 557-582
Global Strategy for the Diagnosis. Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2017. https://goldcopd.org. [Accessed 7 July 2017].
- Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: a randomized, multicentre study in East Asia.Respirology. 2016; 21: 119-127
- Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: a randomized controlled study.Respir Med. 2012; 106: 382-389
- Medication adherence and persistence in chronic obstructive pulmonary disease patients receiving triple therapy in a USA commercially insured population.Int J Chron Obstruct Pulmon Dis. 2019; 14: 343-352
- 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
- Single inhaler triple therapy versus inhaled corticosteroid plus long-acting ²2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial.Lancet. 2016; 388: 963-973
- Once-daily single inhaler triple versus dual therapy in patients with COPD.N Engl J Med. 2018; 378: 167-1680
- 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: 1076-1084
- 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: 747-758
- Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal.Int J Chronic Obstruct Pulmon Dis. 2018; 13: 3971-3981
- The effects of single inhaler triple therapy vs single inhaler dual therapy or separate triple therapy for the management of chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.Int J Chronic Obstruct Pulmon Dis. 2019; 14: 1539-1548
- Adherence to inhaled therapy and its impact on chronic obstructive pulmonary disease (COPD).BMC Pulm Med. 2018; 18: 163
- Adherence in asthma and COPD: new strategies for an old problem.Respir Care. 2018; 63: 818-831
- Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD.N Engl J Med. 2020; 383: 35-48
- Efficacy of budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) versus other inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β(2)-agonist (ICS/LAMA/LABA) triple combinations in COPD: a systematic literature review and network meta-analysis.Adv Ther. 2020; 37: 2956-2975
- Comparisons of efficacy and safety between triple (inhaled corticosteroid/long-acting muscarinic antagonist/long-acting beta-agonist) therapies in chronic obstructive pulmonary disease: systematic review and bayesian network meta-analysis.Respiration. 2021; 100: 631-643
- Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis.BMJ. 2018; 363: k4388
- The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.BMJ. 2009; 339: b2700
- The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.BMJ. 2011; 343: d5928
- 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: 1919-1929
- Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study.Respir Res. 2018; 19: 19
- Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials.Respir Res. 2020; 21: 131
- INTREPID: single- versus multiple-inhaler triple therapy for COPD in usual clinical practice.ERJ Open Res. 2021; 7: 00950-02020
- Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: a double-blind, randomised controlled trial.ERJ Open Res. 2021; 7: 00255-02021
- Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis.Eur Respir J. 2018; 52: 1308-1318
- Adding a LAMA to ICS/LABA therapy: a meta-analysis of triple combination therapy in COPD.Chest. 2019; 155: 758-770
- Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.BMJ Open. 2020; 10e036455
- FULFIL Trial: Once-daily triple therapy for patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2017; 196: 438-446
- 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: 1308-1318
- Inhaler mishandling remains common in real life and is associated with reduced disease control.Respir Med. 2011; 105: 930-938
- A randomized, open-label, single-visit, crossover study simulating triple-drug delivery with Ellipta compared with dual inhaler combinations in patients with COPD.Int J Chron Obstruct Pulmon Dis. 2018; 13: 2515-2523
- Evaluating patient preferences of maintenance therapy for the treatment of chronic obstructive pulmonary disease: a discrete choice experiment in the UK, USA and Germany.Int J Chron Obstruct Pulmon Dis. 2020; 15: 595-604
- Efficacy and safety of budesonide/glycopyrronium/formoterol fumarate versus other triple combinations in COPD: a systematic literature review and network meta-analysis.Adv Ther. 2021; 38: 3089-3112
- Evaluating triple ICS/LABA/LAMA therapies for COPD patients: a network meta-analysis of ETHOS, KRONOS, IMPACT, and TRILOGY studies.Expert Rev Respir Med. 2021; 15: 143-152
- Device errors in asthma and COPD: systematic literature review and meta-analysis.NPJ Prim Care Respir Med. 2017; 27: 22
- Critical inhaler errors in asthma and COPD: a systematic review of impact on health outcomes.Respir Res. 2018; 19: 10
- Patients' perspectives and preferences in the choice of inhalers: the case for Respimat(®) or HandiHaler(®).Patient Prefer Adherence. 2016; 10: 1561-1572
- Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide.Int J Chron Obstruct Pulmon Dis. 2017; 12: 2917-2928
- Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers.J Med Econ. 2011; 14: 486-496
- Once-daily triple therapy in patients with advanced copd: healthcare resource utilization data and associated costs from the FULFIL trial.Adv Ther. 2017; 34: 2163-2172
Article info
Publication history
Published online: May 06, 2022
Accepted:
April 8,
2022
Identification
Copyright
© 2022 Elsevier Inc.
