Efficacy and Safety of Long-acting Beta-2 Agonist and Long-acting Muscarinic Antagonist Combinations in Patients with Chronic Obstructive Pulmonary Disease: Meta-analysis of Phase 3 Randomized Trials

抄録

The aim of the present study was to assess the overall efficacy and safety of long-acting beta-2 agonist （LABA） and long-acting muscarinic antagonist （LAMA） combination therapies （LABA/LAMA） versus monotherapies or placebo in patients with chronic obstructive pulmonary disease （COPD）. The overall efficacy and safety of LABA/LAMA versus LABA, LAMA, or placebo in patients with COPD were assessed by meta-analysis of Phase 3 trials. Primary efficacy outcomes included changes in forced expiratory volume in 1 second （FEV₁₀） from baseline and responder rates using St. George’s Respiratory Questionnaire （SGRQ）. The incidence of serious adverse events （SAEs） was the primary safety outcome. Pooled estimates are presented as standard mean differences （SMD）, odds ratios （ORs）, or risk differences （RDs） with 95% confidence intervals （CIs）. Eleven articles reporting on 13 randomized controlled trials of LABA/LAMA met the criteria for inclusion in the present study. Comparing LABA/LAMA with LAMA, LABA, and placebo, the SMD （95% CI） for a change in FEV₁₀ from baseline was 0.08 （0.06-0.09）, 0.09 （0.07-0.11）, and 0.24 （0.19-0.30）, respectively; the corresponding ORs （95% CI） for changes in SGRQ score were 1.39 （1.24-1.57）, 1.39 （1.06-1.83）, and 1.80 （1.47-2.19）, respectively. The RDs （95% CIs） for SAEs with LABA/LAMA compared with LAMA, LABA, and placebo were －0.01 （－0.02, 0.00）, －0.01 （－0.03, 0.00）, and 0.01 （－0.01, 0.02）, respectively. Pulmonary function and health-related quality of life were significantly higher for LABA/LAMA, and the risk of SAEs did not increase significantly with combination therapy. These results indicate the overall efficacy and safety of LABA/LAMA in patients with COPD.