Budesonide triple therapy significantly lowers exacerbation rates in severe COPD

1. Triple therapy for severe chronic obstructive pulmonary disease (COPD) with budesonide-glycopyrrolate-formoterol was associated with significantly lower risk of COPD exacerbation compared to dual therapy groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Treatment for COPD involves a stepwise approach where treatments are added when necessary to control symptoms and reduce exacerbations. Triple therapy includes an inhaled glucocorticoid, a long-action muscarinic antagonist (LAMA), and a long-acting β₂-agonist (LABA). Tripe therapy is recommended for patients continually experiencing exacerbations from dual therapy of LAMA-LABA or inhaled glucocorticoid-LABA. As such, this study compared the efficacy and safety of the triple therapy of budesonide-glycopyrrolate-formoterol combination and two dual therapies, glycopyrrolate-formoterol (LAMA-LABA) and budesonide-formoterol (inhaled glucocorticoid-LABA). The study determined that patients in the triple therapy group had lower rates of exacerbations compared to the patients in the two dual therapy groups. One limitation of this randomized trial was the higher incidence of pneumonia within the patient population compared to previously published randomized control trials regarding COPD therapies. Nonetheless, this study was strengthened by the long-term patient follow-up between the treatment groups.

Click to read the study in NEJM

Relevant Reading: Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD

In-Depth [randomized controlled trial]: This randomized control trial enrolled 8588 patients in a multicenter study from 25 countries. The study included patients between 40 to 80 years of age, who received at least two inhaled maintenance therapies and had symptomatic COPD. The exclusion criteria for the study included current diagnosis of asthma. The patients were randomized in a 1:1:1:1 ratio to receive 160μg- budesonide triple therapy dose, 320μg- budesonide triple therapy dose, glycopyrrolate-formoterol, or budesonide-formoterol. The primary outcome was the annual rate of moderate to severe COPD exacerbations. Moderate exacerbation was defined as leading to systemic glucocorticoid and/or antibiotic treatment for at least three days. Severe exacerbation was defined as resulting in hospitalization or death. The annual rate for exacerbations was significantly lower with 320μg- budesonide triple therapy dose compared to glycopyrrolate-formoterol (rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83, P<0.0001) and budesonide-formoterol (rate ratio, 0.87; 95% CI, 0.79 to 0.95; P=0.003). Furthermore, no difference was observed between the two triple therapies (rate ratio: 1.00, 95% CI, 0.91 to 1.10). Finally, the risk of death from any cause in the 320μg triple therapy group was 46% lower than the glycopyrrolate-formoterol group (hazard ratio, 0.54; 95% CI, 0.34 to 0.87) and 22% lower than the budesonide-formoterol group (hazard ratio, 0.78; 95% CI, 0.47 to 1.30). Taken together, administration of triple therapy of budesonide-glycopyrrolate-formoterol significantly lowered rates of exacerbations in patients with moderate or severe COPD.

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