Triple versus Dual Inhaler Therapy in Patients with COPD - IMPACT Trial can change COPD Guidelines in 2019

The Informing the Pathway of COPD Treatment (IMPACT) trial, now reported in the The New England Journal of Medicine, aims to fill this gap with a report on the effectiveness of LAMA–LABA–inhaled glucocorticoid treatment, contained in a single inhaler, in COPD.

Background

The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β₂-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid–LABA or LAMA–LABA), are uncertain.

Methods

In this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate–vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium–vilanterol (at doses of 62.5 μg and 25 μg, respectively). Each regimen was administered in a single Ellipta inhaler. The primary outcome was the annual rate of moderate or severe COPD exacerbations during treatment.

Results

The rate of moderate or severe exacerbations in the triple-therapy group was 0.91 per year, as compared with 1.07 per year in the fluticasone furoate–vilanterol group (rate ratio with triple therapy, 0.85; 95% confidence interval [CI], 0.80 to 0.90; 15% difference; P<0.001) and 1.21 per year in the umeclidinium–vilanterol group (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001). The annual rate of severe exacerbations resulting in hospitalization in the triple-therapy group was 0.13, as compared with 0.19 in the umeclidinium–vilanterol group (rate ratio, 0.66; 95% CI, 0.56 to 0.78; 34% difference; P<0.001). There was a higher incidence of pneumonia in the inhaled-glucocorticoid groups than in the umeclidinium–vilanterol group, and the risk of clinician-diagnosed pneumonia was significantly higher with triple therapy than with umeclidinium–vilanterol, as assessed in a time-to-first-event analysis (hazard ratio, 1.53; 95% CI, 1.22 to 1.92; P<0.001).

Conclusions

Triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a lower rate of moderate or severe COPD exacerbations than fluticasone furoate–vilanterol or umeclidinium–vilanterol in this population. Triple therapy also resulted in a lower rate of hospitalization due to COPD than umeclidinium–vilanterol.

full text:

http://www.nejm.org/doi/full/10.1056/NEJMoa1713901