The once-daily fixed-dose combination of olodaterol and tiotropium in the management of COPD: current evidence and future prospects

Abstract

Long-acting bronchodilators are the cornerstone of pharmacologic treatment of chronic obstructive pulmonary disease (COPD). Spiolto^® or Stiolto^® is a fixed-dose combination (FDC) containing two long-acting bronchodilators, the long-acting muscarinic receptor antagonist tiotropium (TIO) and the long-acting β2-adrenoceptor agonist olodaterol (OLO), formulated in the Respimat^® Soft Mist™ inhaler. A total of 13 large, multicentre studies of up to 52 weeks' duration have documented its efficacy in more than 15,000 patients with COPD. TIO/OLO 5/5 µg FDC significantly increases pulmonary function compared with placebo and its respective constituent mono-components TIO 5 µg and OLO 5 µg. TIO/OLO 5/5 µg also results in statistically and clinically significant improvements in patient-reported outcomes, such as dyspnoea, use of rescue medication, and health status. Addition of OLO 5 µg to TIO 5 µg reduces the rate of moderate-to-severe exacerbations by approximately 10%. Compared with placebo and TIO 5 µg, TIO/OLO 5/5 µg significantly improves exercise capacity (e.g. endurance time) and physical activity, the latter increase being reached by a unique combination behavioural modification intervention, dual bronchodilatation and exercise training. Overall, the likelihood for patients to experience a clinically significant benefit is higher with TIO/OLO 5/5 µg than with its constituent mono-components, which usually yield smaller improvements which do not always reach statistical significance, compared with baseline or placebo. This supports the early introduction of TIO/OLO 5/5 µg in the management of patients with symptomatic COPD.

Keywords: COPD; LABA; LAMA; bronchodilatation; dyspnoea; exacerbation; exercise tolerance; hyperinflation; inspiratory capacity; physical activity; spirometry.

Figure 1.

Adjusted weekly mean night-time rescue medication use over 12 weeks in the OTEMTO studies (a) and over 52 weeks in the TONADO studies (b). Reproduced from Ferguson and colleagues, 2017. O, olodaterol; T, tiotropium.

Figure 2.

Adjusted means (±SE) inspiratory capacity (IC) at pre-exercise, at isotime and at end exercise after 6 weeks (combined studies). Reproduced from O’Donnell and colleagues, 2017. As each patient only received four out of five possible treatments, isotimes differ between treatments. O, olodaterol; SE, standard error; T, tiotropium.

Figure 3.

Adjusted geometric mean (± SE) EET in s during constant work-rate cycle ergometry after 6 weeks of treatment (combined studies). *p < 0.05; **p < 0.01; ***p < 0.0001. Reproduced from O’Donnell and colleagues, 2017. EET, exercise endurance time; O, olodaterol; SE, standard error; T, tiotropium.

Figure 4.

Geometric mean EET during endurance shuttle walk test at weeks 8 and 12. Exercise training was stopped after 8 weeks in the SMBM + TIO/OLO 5/5 µg + exercise training arm; all treatment arms continued study medication until week 12. Geometric means baseline exercise endurance test: 243 ± 9 s (week 8); 242 ± 9 s (week 12). Test termination time limit was 20 mins. Reproduced from Troosters and colleagues, 2018. *p < 0.05; **p < 0.01; ***p < 0.001. EET, exercise endurance time; OLO, olodaterol; SE, standard error; SMBM, self-management behaviour modification; TIO, tiotropium.