LABA/LAMA fixed-dose combinations in patients with COPD: a systematic review

Abstract

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

Acknowledgments

We would like to thank Simone Boniface of Springer Health-care Communications who edited the manuscript before submission. This medical writing support was funded by Novartis Farma, Italy. This study and the article-processing charges were supported by an unrestricted grant from Novartis Farma, which was not responsible for the study, data analysis, data interpretation, and manuscript writing.

Disclosure

PR has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis. Her department has been funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. LC has participated as advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received non-financial support by AstraZeneca, received a research grant partially funded by Almirall, Boehringer Ingelheim, and Novartis, and has been a consultant to Edmond Pharma, Verona Pharma, and Zambon. His department has been funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. FB has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, Dompè, GlaxoSmithKline, Lallemand Pharma, Malesci/Guidotti, Menarini Group, Mundipharma, Novartis, Teva, and Zambon. EC has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of AstraZeneca, Boehringer Ingelheim, Guidotti/Malesci, Linde, Menarini Group, and Novartis, and has received financial support for research and for congress attendance from Boehringer Ingelheim, Medical Products Research, and Novartis. GP has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, Dompè, GlaxoSmithKline, Malesci/Guidotti, Menarini Group, Mundipharma, Novartis, Teva, and Zambon. AR has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, Menarini Group, and Novartis. NS has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Guidotti/Malesci, Menarini Group, Mundipharma, Teva, and Zambon, and has received financial support for research and for congress attendance from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Guidotti/Malesci, and Novartis. FDM has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Dompè, Guidotti/Malesci, GlaxoSmithKline, Menarini Group, Novartis, and Zambon, and has received financial support for research from Novartis. MC has participated as a lecturer, speaker, and/or advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, Dey, GlaxoS-mithKline, Kamada, Lallemand Pharma, Menarini Group, Mundipharma, Novartis, Ockham Biotech, Pfizer, Skyepharma, Stallergenes, Teva, Verona Pharma, and Zambon. The authors report no other conflicts of interest in this work.

Author contributions

All authors provided substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data; drafted the article; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All the authors revised the manuscript critically for important intellectual content and approved the version to be published.