Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis

Yayuan Zheng, Jianhong Zhu, Yuyu Liu, Weiguang Lai, Chunyu Lin, Kaifen Qiu, Junyan Wu, Weimin Yao, Yayuan Zheng, Jianhong Zhu, Yuyu Liu, Weiguang Lai, Chunyu Lin, Kaifen Qiu, Junyan Wu, Weimin Yao

Abstract

Objective: To compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).

Design: Systematic review and meta-analysis of randomised controlled trials.

Data sources: PubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.

Eligibility criteria: Randomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available.

Data extraction and synthesis: Data were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).

Results: 21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).

Conclusions: Use of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.

Study registration: Prospero CRD42018077033.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Fig 1
Fig 1
Flow diagram of trial selection
Fig 2
Fig 2
Risk of bias summary for included studies, showing each risk of bias item for every included study
Fig 3
Fig 3
Risk of bias graph presenting each risk of bias item as percentages across all included studies

References

    1. GBD 2016 Risk Factors Collaborators Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1345-422. 10.1016/S0140-6736(17)32366-8
    1. Malerba M, Nardin M, Santini G, Mores N, Radaeli A, Montuschi P. 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;12:1753466618760779. 10.1177/1753466618760779.
    1. Vogelmeier CF, Criner GJ, Martinez FJ, et al. 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;195:557-82. 10.1164/rccm.201701-0218PP
    1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. .
    1. Rojas-Reyes MX, García Morales OM, Dennis RJ, Karner C. Combination inhaled steroid and long-acting beta2-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2016;6:CD008532.
    1. Liu Y, Shi H, Sun X, et al. Benefits of adding fluticasone propionate/salmeterol to tiotropium in COPD: a meta-analysis. Eur J Intern Med 2014;25:491-5. 10.1016/j.ejim.2014.04.007
    1. Kwak MS, Kim E, Jang EJ, Kim HJ, Lee CH. The efficacy and safety of triple inhaled treatment in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis using Bayesian methods. Int J Chron Obstruct Pulmon Dis 2015;10:2365-76.
    1. 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;389:1919-29. 10.1016/S0140-6736(17)30188-5
    1. Lipson DA, Barnhart F, Brealey N, et al. IMPACT Investigators Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med 2018;378:1671-80. 10.1056/NEJMoa1713901
    1. 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;391:1076-84. 10.1016/S0140-6736(18)30206-X
    1. 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;196:438-46. 10.1164/rccm.201703-0449OC
    1. 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;388:963-73. 10.1016/S0140-6736(16)31354-X
    1. Wurst KE, Punekar YS, Shukla A. Treatment evolution after COPD diagnosis in the UK primary care setting. PLoS One 2014;9:e105296. 10.1371/journal.pone.0105296
    1. Simeone JC, Luthra R, Kaila S, et al. Initiation of triple therapy maintenance treatment among patients with COPD in the US. Int J Chron Obstruct Pulmon Dis 2016;12:73-83. 10.2147/COPD.S122013
    1. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700. 10.1136/bmj.b2700
    1. Higgins JP, Altman DG, Gøtzsche PC, et al. Cochrane Bias Methods Group; Cochrane Statistical Methods Group The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
    1. Higgins JPT, Green S, eds. Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions. Wiley-Blackwell, 2008. 10.1002/9780470712184.
    1. Sobieraj DM, Baker WL, Nguyen E, et al. Association of inhaled corticosteroids and long-acting muscarinic antagonists with asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta-analysis. JAMA 2018;319:1473-84. 10.1001/jama.2018.2757
    1. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64:383-94. 10.1016/j.jclinepi.2010.04.026
    1. Aaron SD, Vandemheen KL, Fergusson D, et al. Canadian Thoracic Society/Canadian Respiratory Clinical Research Consortium Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007;146:545-55. 10.7326/0003-4819-146-8-200704170-00152
    1. Cazzola M, Andò F, Santus P, et al. A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD. Pulm Pharmacol Ther 2007;20:556-61. 10.1016/j.pupt.2006.06.001
    1. Hanania NA, Crater GD, Morris AN, Emmett AH, O’Dell DM, Niewoehner DE. Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD. Respir Med 2012;106:91-101. 10.1016/j.rmed.2011.09.002
    1. Hoshino M, Ohtawa J. Effects of adding salmeterol/fluticasone propionate to tiotropium on airway dimensions in patients with chronic obstructive pulmonary disease. Respirology 2011;16:95-101. 10.1111/j.1440-1843.2010.01869.x
    1. Hoshino M, Ohtawa J. Effects of tiotropium and salmeterol/fluticasone propionate on airway wall thickness in chronic obstructive pulmonary disease. Respiration 2013;86:280-7. 10.1159/000351116
    1. Jung KS, Park HY, Park SY, et al. Korean Academy of Tuberculosis and Respiratory Diseases study group. Korea Chronic Obstructive Pulmonary Disease study group Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: a randomized controlled study. Respir Med 2012;106:382-9. 10.1016/j.rmed.2011.09.004
    1. Lee SD, Xie CM, Yunus F, et al. 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;21:119-27. 10.1111/resp.12646
    1. Maltais F, Mahler DA, Pepin V, et al. Effect of fluticasone propionate/salmeterol plus tiotropium versus tiotropium on walking endurance in COPD. Eur Respir J 2013;42:539-41. 10.1183/09031936.00074113
    1. Welte T, Miravitlles M, Hernandez P, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180:741-50. 10.1164/rccm.200904-0492OC
    1. Frith PA, Thompson PJ, Ratnavadivel R, et al. Glisten Study Group Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial. Thorax 2015;70:519-27. 10.1136/thoraxjnl-2014-206670
    1. Siler TM, 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;13:1-10. 10.3109/15412555.2015.1034256
    1. Siler TM, Kerwin E, Sousa AR, Donald A, Ali R, Church A. Efficacy and safety of umeclidinium added to fluticasone furoate/vilanterol in chronic obstructive pulmonary disease: Results of two randomized studies [correction in: Respir Med 2015;109:1493]. Respir Med 2015;109:1155-63. 10.1016/j.rmed.2015.06.006
    1. Sousa AR, Riley JH, Church A, Zhu CQ, Punekar YS, Fahy WA. The effect of umeclidinium added to inhaled corticosteroid/long-acting β2-agonist in patients with symptomatic COPD: a randomised, double-blind, parallel-group study. NPJ Prim Care Respir Med 2016;26:16031. 10.1038/npjpcrm.2016.31
    1. Bremner PR, Birk R, Brealey N, Ismaila AS, Zhu CQ, Lipson DA. 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. 10.1186/s12931-018-0724-0
    1. Meguro M, Barley EA, Spencer S, Jones PW. Development and validation of an improved, COPD-specific version of the St. George respiratory questionnaire. Chest 2007;132:456-63. 10.1378/chest.06-0702
    1. Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2014;(3):CD010115.
    1. Horita N, Goto A, Shibata Y, et al. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev 2017;2:CD012066.
    1. Xia N, Wang H, Nie X. Inhaled long-acting β2-agonists do not increase fatal cardiovascular adverse events in COPD: a meta-analysis. PLoS One 2015;10:e0137904. 10.1371/journal.pone.0137904
    1. Rodrigo GJ, Castro-Rodriguez JA, Nannini LJ, Plaza Moral V, Schiavi EA. Tiotropium and risk for fatal and nonfatal cardiovascular events in patients with chronic obstructive pulmonary disease: systematic review with meta-analysis. Respir Med 2009;103:1421-9. 10.1016/j.rmed.2009.05.020
    1. Melani AS, Bonavia M, Cilenti V, et al. Gruppo Educazionale Associazione Italiana Pneumologi Ospedalieri Inhaler mishandling remains common in real life and is associated with reduced disease control [correction in: Respir Med 2012;106:757]. Respir Med 2011;105:930-8. 10.1016/j.rmed.2011.01.005
    1. Ismaila AS, Birk R, Shah D, et al. Once-daily triple therapy in patients with advanced COPD: healthcare resource utilization data and associated costs from the FULFIL Trial. Adv Ther 2017;34:2163-72. 10.1007/s12325-017-0604-x
    1. 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;10:2207-17.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit