Comparative Effects of LAMA-LABA-ICS vs LAMA-LABA for COPD

Background Triple therapy combinations of a long-acting muscarinic antagonist (LAMA), a long-acting beta2-agonist (LABA), and an inhaled corticosteroid (ICS) for COPD were studied in randomized trials and observational studies, with variable results. We compared the effectiveness and safety of triple therapy with a LAMA-LABA combination in a real-world clinical practice setting. Methods We identified a cohort of patients with COPD during 2002 through 2015, ≥ 55 years of age, from the UK's Clinical Practice Research Datalink. Patients initiating LAMA-LABA-ICS were matched 4:1 on time-conditional propensity scores with patients initiating LAMA-LABA, and followed for 1 year for the occurrence of a moderate or severe COPD exacerbation and severe pneumonia. Results The cohort included 6,921 initiators of LAMA-LABA-ICS matched to 1,932 initiators of LAMA-LABA. The adjusted hazard ratio (HR) of a COPD exacerbation associated with LAMA-LABA-ICS initiation compared with LAMA-LABA initiation was 0.97 (95% CI, 0.87-1.08). For patients with blood eosinophil counts > 6%, the HR was 0.66 (95% CI, 0.46-0.94). For patients with two or more prior exacerbations, it was 0.83 (95% CI, 0.70-0.98). The incidence of severe pneumonia requiring hospitalization was increased with LAMA-LABA-ICS initiation (HR, 1.46; 95% CI, 1.03-2.06). Conclusions In a real-world setting of COPD treatment, the triple combination of LAMA, LABA, and ICS inhalers is generally as effective as combining LAMA and LABA inhalers in preventing COPD exacerbations. However, with the possible exception of patients with significant eosinophilia or frequent exacerbators, a LAMA-LABA combination without ICS may be preferable because it is associated with fewer severe cases of pneumonia.