In patients with chronic obstructive pulmonary disease (COPD), severe or very severe airflow limitation (ie, forced expiratory volume in 1 second [FEV1] <50%), and a history of exacerbation despite maintenance therapy, treatment with the extrafine inhaled corticosteroid-containing triple therapy regimen of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/GLY) was more effective in reducing the rate of moderate to severe disease exacerbations than the dual bronchodilator combination of indacaterol plus glycopyrronium (IND/GLY) over 52 weeks.
Results of the randomized, double-blind, double-dummy, parallel-group TRIBUTE study (ClinicalTrials.gov Identifier: NCT02579850) — the first long-term study that specifically compared the effects of the two treatments — were published recently in The Lancet.
TRIBUTE was conducted at 187 sites across 17 countries. Eligible patients had symptomatic COPD, severe or very severe airflow limitation, at least 1 moderate or severe disease exacerbation in the prior year, and were receiving inhaled maintenance therapy. Following a 2-week run-in period with 1 inhalation of IND/GLY (85 μg/43 μg) daily, participants were randomly assigned, in a 1:1 ratio, to receive 52 weeks of treatment with 2 inhalations of extrafine BDP/FF/GLY (87 μg/5 μg/9 μg) twice daily or 1 inhalation of IND/GLY (85 μg/43 μg) daily. The primary end point was the rate of moderate to severe COPD exacerbations reported across 52 weeks of treatment. Safety was assessed among all participants who received at least 1 dose of study medication.
Between May 29, 2015, and July 10, 2017, a total of 1532 participants were enrolled, with 764 patients in the BDP/FF/GLY group and 768 in the IND/GLY group. Moderate to severe exacerbation rates were 0.50 per patient per year (95% CI, 0.45-0.57) in the BDP/FF/GLY arm vs 0.59 per patient per year (95% CI, 0.53-0.67) in the IND/GLY arm, yielding a significant adjusted rate ratio of 0.848 (95% CI, 0.723-0.995; P =.043) in favor of BDP/FF/GLY.
Adverse events were reported among 64% (490 of 764) of patients in the BDP/FF/GLY arm and 67% (516 of 768) of patients in the IND/GLY arm. Pneumonia was reported in 4% (28 of 764) of patients in the BDP/FF/GLY group vs 4% (27 of 768) of patients in the IND/GLY group.
The investigators concluded that use of extrafine inhaled triple therapy was more effective than dual bronchodilator therapy in reducing the rates of moderate to severe COPD exacerbations, without increasing the risk for pneumonia.
Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial [published online February 8, 2018]. Lancet. doi: 10.1016/S0140-6736(18)30206-X