Efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis.
BACKGROUND
The place of long-acting β agonist/long-acting muscarinic antagonist (LABA/LAMA) combinations in stable patients with COPD is not well defined. The purpose of this study was to systematically review the efficacy and safety of LABA/LAMA combinations.


METHODS
Several databases and manufacturers' websites were searched for relevant clinical trials. Randomised control trials, at least 12 weeks duration, comparing a LABA/LAMA combination with placebo and/or monotherapy were included. The data were pooled using a network as well as a traditional direct comparison meta-analysis.


RESULTS
Twenty-three trials with a total of 27 172 patients were included in the analysis. LABA/LAMA combinations were associated with a greater improvement in lung function, St. George's Respiratory Questionnaire (SGRQ) score, and Transitional Dyspnoea Index (TDI) than monotherapies. LABA/LAMA combinations were associated with a significantly greater proportion of SGRQ and TDI responders than monotherapies (OR 1.23 (95% credible interval (CrI) 1.06-1.39), OR 1.34 (95% CrI 1.19-1.50) versus LABAs and OR 1.24 (95% CrI 1.11-1.36), OR 1.31 (95% CrI 1.18-1.46) versus LAMAs, respectively) and fewer moderate-to-severe exacerbations compared with LABAs (HR 0.82 (95% CrI 0.73-0.93)), but not when compared with LAMAs (HR 0.92 (95% CrI 0.84-1.00)). There were no statistically significant differences associated with LABA/LAMA combinations compared with monotherapies in safety outcomes as well as in severe exacerbations.


CONCLUSIONS
The combination therapy was the most effective strategy in improving lung function, quality of life, symptom scores and moderate-to-severe exacerbation rates, and had similar effects on safety outcomes and severe exacerbations as compared with monotherapies.
Division of Pulmonary, Critical Care and Environmental Medicine, University of Missouri, School of Medicine, Columbia, USA.
Yuji
Y
Oba
Division of Pulmonary, Critical Care and Environmental Medicine, University of Missouri, School of Medicine, Columbia, USA.
Siva T
ST
Sarva
School of Social and Community Medicine, University of Bristol, Bristol, UK.
Sofia
S
Dias
D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012129:Respiratory Function Tests
D058666:Adrenergic beta-2 Receptor Agonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists
COPD Exacerbations; COPD Pharmacology