A Long-acting Muscarinic Antagonist （LAMA） Added to an Inhaled Corticosteroid and Long-acting Beta-2 Agonist Versus LAMA Alone in Moderate-to-severe Chronic Obstructive Pulmonary Disease:

A Systematic Review and Meta-analysis of Randomized Trials

Abstract

We assessed the overall efficacy and safety of a long-acting muscarinic antagonist （LAMA） added to an inhaled corticosteroid （ICS） and long-acting beta-2 agonist （LABA） as a combination therapy （LAMA＋ICS/LABA） versus LAMA monotherapy in patients with chronic obstructive pulmonary disease （COPD）. The overall efficacy and safety of LAMA＋ICS/LABA versus LAMA in patients with COPD were assessed by a meta-analysis of randomized controlled trials （RCTs）. We identified LAMA＋ICS/LABA RCTs by searching PubMed, Scopus, and the Cochrane Library database. Primary efficacy outcomes were changes in forced expiratory volume in 1 second （FEV_1.0） from baseline. Incidences of all adverse events （AAEs） were the primary safety outcomes. Pooled estimates are presented as mean differences （MDs） or risk ratios （RRs） with 95％ confidence intervals （CIs）. Analyses included intention-to-treat cases. Three LAMA＋ICS/LABA RCTs met the criteria for inclusion in this study. The MD, RRs, and their 95％ CIs regarding changes in FEV1.0 for LAMA＋ICS/LABA compared with those of LAMA were 0.08 （0.04 to 0.13）; RRs and 95％ CIs for AAEs of LAMA＋ICS/LABA compared with those of LAMA were 1.03 （0.82 to 1.29）. Conclusions: Pulmonary function was significantly improved in the LAMA＋ICS/LABA group with no significant increase in AAE risk. These results provide important analysis regarding the overall efficacy and safety of LAMA＋ICS/LABA in patients with COPD.