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

Objectives: 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. Methodology: A systematic literature search of randomized-controlled trials published in English up to September 2017 of LABA/LAMA FDCs versus 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 s (FEV1), Transition Dyspnea Index (TDI) scores, St. George's Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (ET), inspiratory capacity (IC) and rescue medication use were evaluated. Results: Twenty-seven 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 versus 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 versus LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/ tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC versus the active comparators. Rescue medication use was significantly reduced by LABA/LAMA FDCs versus the evaluated comparators. LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs versus the monocomponents. Conclusions: 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 versus 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.