The combination of tiotropium and olodaterol did not reduce the exacerbation rate in patients with chronic obstructive pulmonary disease (COPD) as much as expected compared with tiotropium alone, according to the results of the randomized, parallel-group, active-controlled DYNAGITO trial (ClinicalTrials.gov Identifier: NCT02296138), published in the Lancet Respiratory Medicine.
Exacerbations are an important treatment target, as symptomatic exacerbations contribute to poor health status, increased risk for death, and increased healthcare costs. Furthermore, exacerbation frequency is used by the Global Initiative for Chronic Obstructive Lung Disease to assess COPD severity and guide treatment choice.
Peter M. A. Calverley, DSc, from the Clinical Science Centre at the Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom, and colleagues conducted this 52-week, double-blind study of 7880 patients with COPD with a history of exacerbations and randomly assigned them to receive tiotropium-olodaterol (n=3939) or tiotropium (n=3941) once daily. Patients who were using inhaled corticosteroids continued to do so. The study included 818 centers in 51 countries.
The rate of moderate and severe exacerbations was lower with tiotropium-olodaterol than tiotropium (rate ratio, 0.93; P =.0498), but did not meet the targeted 0.01 significance level. The proportion of patients who reported adverse events was similar in both groups.
The authors noted that although it has previously been shown that adding olodaterol to tiotropium improves lung function, symptoms, and quality of life compared with tiotropium monotherapy, this large trial was the first of its kind to address the question of whether the addition of a long-acting beta-agonist to tiotropium can further benefit in terms of reducing exacerbations in patients with COPD. The authors added that although the reduction in exacerbations was smaller than anticipated, there were larger improvements in some subgroups of patients, such as those receiving triple therapy at baseline, and in exacerbations that required oral corticosteroids.
Disclosures: This study was funded by Boehringer Ingelheim International GmbH.
Calverley PMA, Anzueto AR, Carter K, et al. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial. Lancet Respir Med. 2018;6(5):337-344.