Triple inhaler therapy associated with reduced COPD exacerbations, higher rates of pneumonia
Results of the systematic review and meta-analysis suggest that triple inhaler therapy should be limited to patients with more severe symptoms of chronic obstructive pulmonary disease (COPD) that cannot be adequately managed by dual therapy, the authors said.
Triple inhaler therapy for chronic obstructive pulmonary disease (COPD) was associated with lower rates of moderate or severe exacerbations but higher rates of pneumonia versus dual therapy or monotherapy, according to a new study.
Researchers performed a systematic review and meta-analysis of randomized controlled trials published through mid-April 2018 that compared triple therapy with dual therapy or monotherapy in patients with COPD. The primary outcomes in the included studies were moderate or severe exacerbations, and other efficacy outcomes included severe exacerbations, death, FEV1, safety, and quality of life. Results were published on Nov. 6 by The BMJ.
Twenty-one trials in 19 publications were included in the review and meta-analysis. Six trials used fixed triple therapy, in which a long-acting muscarinic antagonist (LAMA), a long-acting beta-agonist (LABA), and an inhaled corticosteroid were contained in one inhaler, and 15 trials used separate triple therapy, in which the three drugs were administered with different inhalers. Ten trials compared triple therapy with LAMA monotherapy, three trials compared triple therapy with LAMA and LABA dual therapy, 11 trials compared triple therapy with dual therapy with inhaled corticosteroids and LABA, and two trials compared fixed triple therapy with separate triple therapy (some trials included multiple comparisons).
An association was seen between triple therapy and significantly lower rates of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio, 0.71; 95% CI, 0.60 to 0.85), dual therapy with LAMA and LABA (rate ratio, 0.78; 95% CI, 0.70 to 0.88), and dual therapy with inhaled corticosteroids and LABA (rate ratio, 0.77; 95% CI, 0.66 to 0.91). Trough levels of FEV1 and quality of life appeared to be better with triple therapy, while rates of pneumonia were significantly higher versus dual therapy with LAMA and LABA (relative risk, 1.53; 95% CI, 1.25 to 1.87).
The researchers noted that the trials used different inhalers and different dosing regimens and that the study results had a high level of heterogeneity, among other limitations. However, they concluded that triple therapy was associated with improved rates of moderate or severe exacerbations, better lung function, and better health-related quality of life than dual therapy or LAMA monotherapy. They cautioned that triple therapy did not appear to improve survival and could increase risk for pneumonia.
“Therefore, triple therapy should be limited to patients with more severe COPD symptoms that cannot be adequately managed by dual therapy,” they wrote. “Attempts should be made to identify patients with COPD phenotypes (eg, eosinophil levels, patient characteristics, and exacerbation history) most likely to respond to the triple therapy.”