Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis

We performed a meta-analysis to compare the impact of triple combination therapy with inhaled corticosteroids (ICS), long-acting β2-agonists (LABAs) and long-acting muscarinic receptor antagonists (LAMAs) versus LABA/LAMA combination therapy or single long-acting bronchodilator therapy in chronic obstructive pulmonary disease. The ICS/LABA/LAMA combination reduced the risk of exacerbation (relative risk 0.70, 95% CI 0.53-0.94) and improved trough forced expiratory volume in 1 s (mean difference in mL +37.94, 95% CI 18.83-53.89) versus LABA/LAMA combination therapy. The protective effect of triple combination therapy versus LABA/LAMA combination therapy against risk of exacerbation was greater in patients with blood eosinophil counts ≥300 cells·µL-1 (relative risk 0.57, 95% CI 0.48-0.68). While ∼38 patients had to be treated for 1 year with ICS/LABA/LAMA combination therapy to prevent one exacerbation compared to LABA/LAMA combination therapy, the number needed to treat (NNT) was ∼21 when compared to single long-acting bronchodilator therapy. The person-based NNT per year of ICS/LABA/LAMA combination therapy versus LABA/LAMA combination therapy was significantly (p<0.05) lower in patients with eosinophil counts ≥300 cells·µL-1 (NNT value: 8.58) than in those with counts <300 cells·µL-1 (NNT value: 46.28). The risk of pneumonia did not differ between ICS/LABA/LAMA combination therapy and its comparators. The number needed to harm was ∼195. This meta-analysis suggests that patients on single long-acting bronchodilator therapy or LABA/LAMA combination therapy, who still have exacerbations and have blood eosinophil counts ≥300 cells·µL-1, could benefit from ICS/LABA/LAMA combination therapy.