Once-daily treatment with combined fluticasone furoate-vilanterol was associated with a lower rate of chronic obstructive pulmonary disease (COPD) exacerbations than usual care, an industry-funded trial has shown.
Researchers performed a controlled effectiveness trial in 75 general practices in the United Kingdom to evaluate the effectiveness and safety of combination treatment with these drugs versus usual care with existing maintenance therapy. The trial was funded by GlaxoSmithKline. Between March 13, 2012, and Oct. 23, 2014, patients were recruited if they were 40 years of age and older, had a documented diagnosis of COPD from a general practitioner, had had at least 1 COPD exacerbation in the previous 3 years, and were taking regular maintenance inhaler therapy (1 or more long-acting bronchodilators; inhaled glucocorticoids, alone or with a long-acting bronchodilator; or a combination of inhaled glucocorticoids, a long-acting beta-agonist, and a long-acting muscarinic antagonist). Those who had had an exacerbation in the preceding 2 weeks and those with long-term use of glucocorticoids were excluded. Patients were randomly assigned to receive a once-daily inhaled combination of fluticasone furoate, 100 µg, and vilanterol, 25 µg, or to continue usual care with maintenance therapy.
The open-label parallel-group trial was conducted over 12 months. The primary outcome was the rate of moderate or severe exacerbations in patients who had had an exacerbation in the year before the trial. Rates of primary care contact (i.e., with a general practitioner, nurse, or other health care professional) and secondary care contact (i.e., an inpatient admission, outpatient visit with a subspecialist, or an ED visit) were secondary outcomes, along with modification of initial trial treatment and the rate of exacerbations in those with an exacerbation in the 3 years before the trial. The study results were published online Sept. 4 by the New England Journal of Medicine.
A total of 3,161 patients with COPD were screened for the study, and 2,802 were randomly assigned to a study group. Of the total trial population of 2,799 patients (3 patients assigned to the fluticasone furoate-vilanterol group did not take any doses of the trial medication), 2,269 (81%) had at least 1 moderate or severe exacerbation in the year before the trial and comprised the population for the primary effectiveness analysis. Among the overall trial population, 1,291 patients in the fluticasone furoate-vilanterol group and 1,309 in the usual care group completed the trial; these numbers were 1,051 and 1,056, respectively, in the primary effectiveness analysis.
Among the patients included in the primary effectiveness analysis, the fluticasone furoate-vilanterol group had a rate of 1.74 moderate or severe exacerbations per year versus 1.90 per year in the usual care group, meaning that the rate in the fluticasone furoate-vilanterol group was 8.4% lower (95% CI, 1.1% to 15.2%) (P=0.02). An 8.4% rate difference (95% CI, 1.4% to 14.9%) was also seen in the overall trial population (1.50 moderate or severe exacerbations per year in the fluticasone furoate-vilanterol group versus 1.64 per year in the usual care group) (P=0.02). No significant difference was seen in the rate of first moderate or severe exacerbation (hazard ratio, 0.93 [95% CI, 0.85 to 1.02] for fluticasone furoate-vilanterol vs. usual care) or the rate of first severe exacerbation (hazard ratio, 1.27; 95% CI, 0.98 to 1.66; P=0.08) in time-to-event analysis or in the rate of severe exacerbations (0.09 and 0.08 exacerbation per year, respectively) among the entire study population.
There was no significant difference between the fluticasone furoate–vilanterol group and the usual-care group in the annual rate of COPD-related contact with primary care, but the former did have a higher annual rate of all primary care contacts (12.3%; 95% CI, 5.4 to 19.6). Four hundred four patients in the fluticasone furoate-vilanterol group (29%) and 383 patients in the usual care group (27%) had serious adverse events during treatment. One patient in each group died of a serious adverse event thought to be related to the trial medication (pneumonia in the usual care group and pulmonary embolism and deep venous thrombosis in the fluticasone furoate-vilanterol group).
The authors noted that their trial results should be interpreted carefully and that the trial's open-label design could have introduced bias. However, they also stated that the trial was conducted in a largely unsupervised manner over a year and as such reflects factors involved in usual clinical care, such as adherence and dosing frequency. They concluded that patients in general practice with COPD who were at higher risk for exacerbations benefited from once-daily inhaled therapy with fluticasone furoate-vilanterol without an increased risk for serious adverse events. “Future effectiveness studies are likely to influence clinical guidelines, not only for COPD but for many other chronic diseases,” the authors predicted.