Triple Inhaled Therapy Provides a Small Reduction in Moderate COPD Exacerbations, No Effect on Severe Exacerbations

Clinical Question

Is triple inhaled therapy for chronic obstructive pulmonary disease (COPD) more effective than dual inhaled therapy?

Bottom Line

Triple inhaled therapy, with budesonide (Pulmicort) in a dose of either 160 mcg or 320 mcg daily plus a long-acting muscarinic antagonist (LAMA) and a long-acting beta₂ agonist (LABA), reduces moderate exacerbations (a need for an antibiotic or steroid for three or more days) more than either a LAMA plus a LABA or inhaled corticosteroid plus a LABA, but the difference is small and of questionable clinical significance. There is no clinically important difference in severe exacerbations and no difference in mortality. Another study found a mortality reduction for triple therapy, with numbers needed to treat for one year of 120 (vs. a LAMA plus a LABA) and 358 (vs. an inhaled corticosteroid plus a LABA). (Level of Evidence = 1b)

Synopsis

Triple inhaled therapy for COPD consists of an inhaled corticosteroid, a LAMA, and a LABA. The inhaled corticosteroid in this study was budesonide, the LAMA was glycopyrrolate, 9 mcg twice daily, and the LABA was formoterol (Breztri Aerosphere), 4.8 mcg twice daily. The study randomized 8,588 patients to one of four regimens: triple therapy with 320 mcg of budesonide daily, triple therapy with budesonide, 160 mcg daily, dual therapy with a LAMA plus a LABA, and dual therapy with an inhaled corticosteroid plus a LABA. Participants had COPD that was not well-controlled (forced expiratory volume in one second [FEV₁] less than 0.70 postbronchodilator, and already taking at least two inhaled agents) and had experienced at least one moderate or severe exacerbation in the past year. Participants had a mean age of 64 years, approximately 60% were men, and 41% were current smokers. Approximately 30% of participants had a postbronchodilator FEV₁ of 50% to 80% of predicted, 60% were at 30% to 50% of predicted, and 10% were less than 30% of predicted.

The primary outcome was the rate of moderate or severe ex