Fixed Combination of Tiotropium/Olodaterol in SMI Inhaler and Its Benefits in COPD Treatment

Introduction

Various types of inhalers are utilized in the treatment of COPD. Some of these inhalers require patients to exert significant inspiratory effort to activate the inhaler or fully utilize the dose of the drug, which is problematic for many COPD patients. The Respimat inhaler requires no or minimal inspiratory effort. Mechanical energy from a tensioned spring helps release the active substance in the form of a fine mist. Compared to powder inhalers and aerosol dispensers, this type of inhaler shows low deposition of the drug in the oropharyngeal area and high deposition in the lungs.

The Respimat inhalation system also delivers a fixed combination of tiotropium (a bronchodilator from the long-acting anticholinergic − LAMA group) and olodaterol (a bronchodilator from the long-acting β₂-agonists − LABA group). This combination has been proven to reduce the risk of COPD exacerbations and improve lung function and quality of life in the long term.

Methodology and Study Course

The presented study evaluated the efficacy of COPD treatment using a fixed combination of tiotropium/olodaterol and assessed whether this therapy using the Respimat inhaler is suitable for all COPD patients regardless of their peak inspiratory flow – PIF. It was a randomized, double-blind, placebo-controlled multicenter study involving 213 patients over 40 years old with moderate to severe COPD.

Patients were randomized into two groups and received either the tiotropium/olodaterol combination (5 µg/5 µg) or placebo. The first group included 106 individuals (PIF < 60 l/min in 55 patients, PIF ≥ 60 l/min in 51), and the control group consisted of 107 individuals (PIF < 60 l/min in 55 patients, PIF ≥ 60 l/min in 52). After 4 weeks of therapy, changes in one-second lung vital capacity − FEV₁ AUC_{0−3 hours} and trough FEV₁ were assessed compared to pre-treatment values.

Results

The change in FEV₁ AUC_{0−3 h} after 4 weeks of treatment in the group inhaling the fixed combination of tiotropium and olodaterol compared to placebo was 336 ml (95% CI 246–425 ml; p < 0.0001) in patients with baseline PIF < 60 l/min and 321 ml (95% CI 233–409 ml; p < 0.0001) in patients with baseline PIF ≥ 60 l/min. For the trough FEV₁ indicator, the average change compared to baseline measurement was 201 ml (95% CI 117–286 ml; p < 0.0001) in the group with PIF < 60 l/min and 217 ml (95% CI 135–299 ml; p < 0.0001) in patients with PIF ≥ 60 l/min.

Safety and tolerability of the therapy were assessed by monitoring the incidence of adverse events. During the 4-week monitoring, adverse events were recorded in a total of 30 individuals, most commonly cough, rhinitis, epistaxis, or shortness of breath. The most frequent adverse events in the experimental group were noted in 5 individuals, and in the control group, in 7 individuals.

Summary and Conclusion

According to the findings of the presented study, inhalation therapy with a fixed combination of tiotropium/olodaterol has a clear effect compared to placebo and significantly improves lung function. An SMI type inhaler, which creates a fine mist, can be used in COPD patients regardless of their PIF parameter value.

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Source: Mahler D. A., Ludwig-Sengpiel A., Ferguson G. T. et al. TRONARTO: a randomized, placebo-controlled study of tiotropium/olodaterol delivered via soft mist inhaler in COPD patients Stratified by peak inspiratory flow. Int J Chron Obstruct Pulmon Dis 2021; 16: 2455–2465, doi: 10.2147/COPD.S324467.