The epoch of dual bronchodilation: the first direct comparisons and meta-analyzes

Abstract

The aim of this review was to summarize recently published data on dual bronchodilation in patients with chronic obstructive pulmonary disease (COPD). Four fixed combinations of long-acting β2-agonists (LABA) and long-acting muscarinic receptor agonists (LAMA), vilanterol/umeclidinium, olodaterol/tiotropium, glycopyrronium/indacaterol, and formoterol/aclidinium, have been approved by regulatory organs of Russia, Europe, and USA. Indirect comparisons of effects of these combinations on forced expiratory parameters showed equal bronchodilation. Inhalational devices for each combination are different. Respimat soft-mist inhaler was characterized by high and effective drug deposition in the lungs, Ellipta dry powder inhaler was easy-to-use and was characterized by a low rate of crucial mistakes with the inhaler technique. We found three published direct comparative studies of LABA/LAMAs. An open-label direct non-inferiority study of vilanterol/umeclidinium vs olodaterol/tiotropium showed advantages of vilanterol/umeclidinium Ellipta inhaler. Two similar direct comparative trials of glycopyrronium/indacaterol 27.5/15.6 µg b.i.d. vs vilanterol/umeclidinium 25/62.5 µg q.d. did not reach the primary endpoint of non-inferiority; secondary endpoints were descriptive. Between-group differences were small and statistically insignificant. Conclusion. The results of meta-analyses and direct comparative trials are not sufficient to choose the best dual bronchodilator as the drug efficacy is determined by multiple factors. A direct open-label comparative trial that demonstrated superiority of vilanterol/umeclidinium Ellipta inhaler over olodaterol/tiotropium Respimat inhaler became the first step on this way.