Triple inhaled therapy for COPD effective for selected patients

Reference

Calzetta L, Cazzola M, Matera MG, Rogliani P. Adding a LAMA to ICS/LABA therapy: A meta-analysis of triple combination therapy in COPD. Chest 2019;155(4):758-770.

Synopsis

The 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for management of COPD now recommend the consideration of triple inhaled therapy for patients whose disease is not well controlled by dual inhaler therapy (LAMA/LABA or LAMA/ICS). This systematic review attempted to quantify the potential benefit by identifying 13 randomized controlled trials from 11 publications that compared LAMA/LABA/ICS with LABA/ICS in a total of 15,519 patients. Included studies had a duration of 2 weeks to 52 weeks. Patients in the studies had a mean postbronchodilator FEV1 of 37% to 59% of predicted, In 3 of the largest studies, patients must have had at least 1 acute exacerbation of COPD to be included. Study quality, assessed by the now somewhat dated Jadad score, was rated as good although no detail is given. Four of the studies had more than 1000 patients, including one with 8285 patients. The patients randomized to receive triple therapy experienced fewer moderate to severe acute exacerbations of COPD than those assigned to ICS/LABA alone (relative risk 0.78, 95% CI 0.71 - 0.85). The authors estimate a number needed to treat of 23 to prevent one exacerbation over a 1-year period. Favorable changes in physiologic parameters were also observed, with no increase in serious or cardiovascular adverse events. Counterintuitively, increasing age and increasing pack-years were associated with less benefit of triple therapy in the meta-regression analysis, as was being female. Heterogeneity for the outcome of acute exacerbations was moderate (I^2 = 44%), although the point estimate for relative risk was less than 1.0 for 12 of 13 studies.