Extrafine fixed triple therapy had clinically beneficial effects on quality of life, hyperinflation, forced expiratory volume1 and exacerbations in patients with COPD when compared with long-acting muscarinic antagonist monotherapy, according to research recently published in The Lancet.
“Few studies have addressed the added value of triple therapy for preventing exacerbations,” Jørgen Vestbo, MD, FRCP, FERS, of the division of infection, immunity and respiratory infection at the University of Manchester, England, and colleagues wrote. “Although two 12-week studies have suggested that triple therapy can provide a greater reduction in exacerbations compared with a long-acting muscarinic antagonist, longer trials are needed to assess moderate and severe exacerbations, not least because of their marked seasonality.”
Vestbo and colleagues compared treatment with extrafine beclometasone dipropionate, formoterol fumarate and glycopyrronium bromide (fixed triple) with beclomethasone dipropionate, formoterol fumarate plus tiotropium (open triple), and tiotropium alone in 2,671 patients with COPD. The patients had a postbronchodilator FEV1 of less than 50%, at least one moderate-to-severe COPD exacerbation in the previous 12 months, and a COPD Assessment Test total score of at least ten.
Patients underwent a 2-week run-in period receiving one inhalation per day with a single-dose dry-powder inhaler of open-label 18 g tiotropium, then were randomly assigned to 52 weeks of treatment with tiotropium, fixed triple, or open triple. Randomization was determined by severity of airflow limitation and country. The primary endpoint was moderate-to-severe COPD exacerbation rate; a secondary endpoint was change from baseline in pre-dose FEV1 at week 52.
Researchers found that moderate-to-severe exacerbation rates were 0.46 (95% CI, 0.41–0.51) for fixed triple, 0.57 (0.52–0.63) for tiotropium, and 0.45 (0.39–0.52) for open triple; fixed triple was superior to tiotropium (RR = 0.8; 95% CI, 0.69–0.92). For week 52 predose FEV1, fixed triple was superior to tiotropium (mean difference = 0.061 L; P < .0001) and noninferior to open triple (–0.003 L; P = .85). Extrafine fixed triple also resulted in a 20% (95% CI, 8–31) reduction in the rate of moderate-to-severe COPD exacerbations compared with tiotropium.
Adverse events were reported by 55% of the patients on fixed triple, 58% of the patients on tiotropium, and 58% on open triple, with the most serious of these being COPD, pneumonia, ischemic heart disease and cardiac failure.
“To our knowledge, this is the first long-term study specifically designed to evaluate the effect of a single inhaler triple therapy vs. long-acting muscarinic antagonist therapy on the rate of exacerbations in a population at high exacerbation risk,” Vestbo and colleagues wrote. “By comparison with long-acting muscarinic antagonist alone, triple therapy with an inhaled corticosteroid, a long-acting -agonist and a long-acting muscarinic antagonist in a single inhaler reduces the rate of COPD exacerbations in this high-risk population, together with improvements in lung function, and in a range of other clinically relevant measures.” – by Janel Miller
Disclosure: Vestbo reports personal fees from Chiesi Farmaceutici, GlaxoSmithKline, Boehringer-Ingelheim, Novartis, and AstraZeneca. Please see the study for a list of the other authors’ relevant disclosures.