Clinical Pearls & Morning Reports
The IMPACT trial was a phase 3, randomized, double-blind, parallel-group, multicenter trial involving patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations. The primary objective was to evaluate the effects of 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a long-acting muscarinic antagonist [LAMA]) at a dose of 62.5 μg, and vilanterol (a long-acting β2-agonist [LABA]) at a dose of 25 μg (triple therapy), as compared with fluticasone furoate–vilanterol (at doses of 100 μg and 25 μg, respectively) or the dual bronchodilator umeclidinium–vilanterol (at doses of 62.5 μg and 25 μg, respectively), on the rate of moderate or severe COPD exacerbations. Read the latest NEJM Original Article here.
Q: When is the use of triple inhaled therapy for COPD recommended?
A: Triple inhaled therapy for COPD is recommended in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) management strategy for COPD in patients who have clinically significant symptoms despite treatment with an inhaled glucocorticoid–LABA or LAMA–LABA and who are at increased risk for frequent or severe exacerbations. Although studies have shown that triple inhaled therapy has positive effects on lung function and COPD symptoms as compared with dual therapy, its use until recently has required patients to use multiple inhalers several times per day. Recently, single inhalers containing an inhaled glucocorticoid, a LABA, and a LAMA have been developed; these inhalers offer potential advantages in practicality and adherence to therapy. However, the effectiveness of combination inhaled therapies has not been comprehensively evaluated in patients with COPD who have the highest symptom burden.
Q: How effective is once-daily single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol in reducing moderate to severe COPD exacerbations?
A: In the IMPACT trial, once-daily single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol resulted in a significantly lower rate of moderate or severe COPD exacerbations and better lung function and health-related quality of life than dual therapy with fluticasone furoate–vilanterol or the dual bronchodilator umeclidinium–vilanterol among patients with symptomatic COPD and a history of exacerbations. The rate of moderate or severe exacerbations during treatment among patients assigned to triple therapy was 0.91 per year, as compared with 1.07 per year among those assigned to fluticasone furoate–vilanterol (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 among those assigned to umeclidinium–vilanterol (rate ratio with triple therapy, 0.75; 95% CI, 0.70 to 0.81; 25% difference; P<0.001).
A: In the IMPACT trial, the annual rate of moderate or severe exacerbations was lower with triple therapy than with either dual-therapy combination, regardless of eosinophil level, although a greater reduction in the exacerbation rate was observed in patients with eosinophil levels of at least 150 cells per microliter.
A: Overall, the adverse-event profile of triple therapy was similar to that of the dual-therapy comparators, and there were no new safety findings associated with the use of an inhaled glucocorticoid, a LAMA, or a LABA in combination. 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).