Background: The Global Initiative for Obstructive Lung Disease (GOLD) recommends triple therapy with inhaled corticosteroids, long-acting beta2-adrenoceptor agonists (LABA), and long-acting muscarinic receptor antagonists (LAMA) for patients with severe COPD who have frequent exacerbations despite treatment with a LABA and LAMA. Triple therapy has been shown to improve forced expiratory volume in 1 second (FEV1), but its effect on preventing exacerbations has not been well documented in previous meta-analyses.
Study design: Meta-analysis.
Setting: Studies published on PubMed, Embase, Cochrane Library website, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases.
Synopsis: 21 randomized, controlled trials of triple therapy in stable cases of moderate to very severe COPD were included in this meta-analysis. Triple therapy was associated with a significantly greater reduction in the rate of COPD exacerbations, compared with dual therapy of LAMA and LABA (rate ratio, 0.78; 95% confidence interval, 0.70-0.88), inhaled corticosteroid and LABA (rate ratio, 0.77; 95% CI, 0.66-0.91), or LAMA monotherapy (rate ratio, 0.71; 95% CI, 0.60-0.85). Triple therapy was also associated with greater improvement in FEV1.
There was a significantly higher incidence of pneumonia in patients using triple therapy, compared with those using dual therapy (LAMA and LABA), and there also was a trend toward increased pneumonia incidence with triple therapy, compared with LAMA monotherapy. Triple therapy was not shown to improve survival; however, most trials lasted less than 6 months, which limits their analysis of survival outcomes.
Bottom line: In patients with advanced COPD, triple therapy is associated with lower rates of COPD exacerbations and improved lung function, compared with dual therapy or monotherapy.
Citation: Zheng Y et al. Triple therapy in the management of chronic obstructive pulmonary disease: Systemic review and meta-analysis. BMJ. 2018;363:k4388.
Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.