The studies, published in the journal The Lancetsuggest that inhaled triple therapy, consisting of an inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta2-agonist, reduces exacerbations in patients with severe chronic obstructive pulmonary disease (COPD).

Triple therapy is commonly used in clinical practice despite the limited evidence to support its superiority over dual bronchodilation. No studies have directly compared single-inhaler triple therapy against single-inhaler dual bronchodilator therapy for reducing exacerbations.

Dr. Alberto Papi from the University of Ferrara, Italy, and colleagues compared single-inhaler triple therapy with an extra fine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium versus single-inhaler dual bronchodilator therapy with indacaterol plus glycopyrronium.

The study was a 52-week randomized trial of 1,532 COPD patients (mean age, about 65) who had severe or very severe airflow limitation. The adjusted rates of moderate-to-severe COPD exacerbations were 0.50 per patient per year for triple-therapy patients and 0.59 per patient per year for dual-therapy patients, a 15.2% reduction (P=0.043).

Patients with chronic bronchitis experienced significant reductions in COPD exacerbations with triple therapy, compared with dual therapy, but patients with emphysema did not. Triple therapy significantly reduced the exacerbation rate among patients with eosinophil fractions of at least 2%, but not in those with lower eosinophil fractions.

Compared with dual therapy, triple therapy produced significantly larger improvements in FEV1 and in St. George's Respiratory Questionnaire total scores. The use of rescue medication and the proportion of patients who had adverse events, including pneumonia, were similar between the two treatment groups.

“It is important to remember that the patients enrolled in TRIBUTE were at the most severe end of the COPD spectrum since they had severe or very severe airflow limitation (FEV1 <50% of reference), were symptomatic at screening despite treatment (COPD Assessment Test score >=10), and had experienced at least one documented moderate or severe COPD exacerbation in the previous year,” notes Dr. Alvar Agusti of the University of Barcelona, Spain, in a linked editorial.

“This means that the results of TRIBUTE only apply to this specific population of patients and cannot be generalized to other patients with milder COPD,” he said. "It will be of great interest to compare these results with those of a similar study, IMPACT (NCT02164513), that is likely to be published soon."