LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis
Received 17 December 2016
Accepted for publication 30 January 2017
Published 17 March 2017 Volume 2017:12 Pages 907—922
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Professor Hsiao-Chi Chuang
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Gustavo J Rodrigo,1 David Price,2,3 Antonio Anzueto,4,5 Dave Singh,6 Pablo Altman,7 Giovanni Bader,8 Francesco Patalano,8 Robert Fogel,7 Konstantinos Kostikas8
1Departamento de Emergencia, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay; 2Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK; 3Observational and Pragmatic Research Institute, Singapore; 4University of Texas Health Science Center, 5South Texas Veterans Health Care System, San Antonio, TX, USA; 6Medicines Evaluation Unit, National Institute for Health Research Respiratory and Allergy Clinical Research Facility, University Hospital of South Manchester NHS Foundation Trust, University of Manchester, Manchester, England, UK; 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 8Novartis Pharma AG, Basel, Switzerland
Background: Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments. The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.
Methods: This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only). Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
Results: Eighteen studies (23 trials) were eligible (N=20,185). LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively). LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively). LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]). Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]). LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).
Conclusion: The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD. These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.
Keywords: LABA/LAMA combinations, COPD, LAMA, LABA/ICS, meta-analysis
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]
Other article by this author:
The asthma–COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?
Kostikas K, Clemens A, Patalano F
Published Date: 16 June 2016