Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial
Peter M A Calverley, Antonio R Anzueto, Kerstine Carter, et al.
Lancet Respir Med 2018; online ahead of print
For patients with chronic obstructive pulmonary disease (COPD) requiring combination bronchodilator therapy, the combination of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is considered the preferred option. This double-blind randomised controlled trial from Peter Calverley and colleagues explored whether the combination of the LABA tiotropium and the LAMA olodaterol was effective in reducing the rate of COPD exacerbations in the study population, compared with tiotropium alone.
A total of 9,009 patients from 51 countries were screened, of whom 7,880 were treated. Patients were aged 40 years or older with a diagnosis of COPD, a smoking history of more than 10 pack-years, stable airflow obstruction, and a history of at least one moderate or severe exacerbation in the preceding year.
To the surprise of the authors, the combination treatment did not perform as well as expected. There was no significant difference between combination and tiotropium alone in the rate of moderate and severe exacerbations. The time to first exacerbation was also not significantly different.
Some benefits were seen in post-hoc analyses: the rate of exacerbations treated with corticosteroids (with or without antibiotics) was lower in the combination group, and among patients who had been receiving inhaled corticosteroids (ICS) as maintenance treatment at baseline, the risk of exacerbations was lower with combination therapy than tiotropium alone.
The authors suggested a few reasons why the combination therapy did not demonstrate the expected benefit. The variance in the study population was higher than expected, and there was differential study withdrawal between treatment arms, both of which may have had an impact on the treatment effect size.
This study was funded by Boehringer Inhelheim International GmbH; some of the paper authors are employees of Boehringer Ingelheim.