LABA/LAMA fixed-dose combinations in patients with COPD: a systematic review
Received 10 April 2018
Accepted for publication 30 July 2018
Published 4 October 2018 Volume 2018:13 Pages 3115—3130
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Charles Downs
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Paola Rogliani,1 Luigino Calzetta,1 Fulvio Braido,2 Mario Cazzola,1 Enrico Clini,3 Girolamo Pelaia,4 Andrea Rossi,5 Nicola Scichilone,6 Fabiano Di Marco7
1Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; 2Department of Internal Medicine, IRCCS San Martino Genoa University Hospital, Genoa, Italy; 3Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy; 4Department of Medical and Surgical Sciences, Section of Respiratory Diseases, Magna Græcia University, Catanzaro, Italy; 5Pulmonary Unit, University of Verona, Verona, Italy; 6Department of Internal Medicine, University of Palermo, Palermo, Italy; 7Department of Health Sciences, Università degli Studi di Milano, Respiratory Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy
Objectives: The aim of this study was to assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD.
Materials and methods: A systematic literature search of randomized controlled trials published in English up to September 2017 of LABA/LAMA FDCs vs LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus, and Google Scholar. Outcomes including forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index (TDI) scores, St George’s Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (endurance time [ET]), inspiratory capacity (IC), and rescue medication use were evaluated.
Results: In total, 27 studies were included in the review. LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS. These effects were maintained over time. Significant improvements with LABA/LAMA FDCs vs each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected. Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority vs LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC vs the active comparators. Rescue medication use was significantly reduced by LABA/LAMA FDCs vs the evaluated comparators. LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs vs the monocomponents.
Conclusion: Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET, and IC. So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority vs LABA, LAMA, and LABA/ICS FDCs across the evaluated outcomes. LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety.
Keywords: LABA, LAMA, fixed-dose combination, COPD, systematic review
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