Efficacy of tiotropium-olodaterol fixed-dose combination in COPD

Abstract

Tiotropium-olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA) and a long-acting β₂-agonist (LABA), commercialized under the name of Spiolto or Stiolto. The efficacy of tiotropium-olodaterol 5-5 μg once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration. Tiotropium-olodaterol 5-5 μg not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance. Improvements exceeded the minimal clinically important difference (MCID) for forced expiratory volume in 1 second (FEV₁), dyspnea, and quality of life. Differences between tiotropium-olodaterol 5-5 μg and the respective monocomponents were statistically significant for FEV₁, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID. However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life. Moreover, tiotropium-olodaterol 5-5 μg was significantly more effective than salmeterol-fluticasone (FDC) twice daily at improving pulmonary function. Differences between tiotropium-olodaterol and other LAMA/LABA FDCs were not observed for FEV₁ or other efficacy markers. Therefore, tiotropium-olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy.

Keywords: COPD; LABA; LAMA; bronchodilatation; dyspnea; exacerbation; exercise tolerance; spirometry.

Figure 1

Adjusted mean FRC (A) and RV (B) responses at 6 weeks ± SE, measured by body plethysmography at 2 hours 30 minutes (02:30) and 22 hours 30 minutes postdose. Notes: *P<0.05 versus placebo; **P<0.0001 versus placebo; ^#P<0.05 versus all monotherapies; ^##P<0.01 versus all monotherapies. Reproduced from Beeh KM, Westerman J, Kirsten AM, et al. The 24-h lung-function profile of once-daily tiotropium and olodaterol fixed-dose combination in chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2015;32:53–59. Abbreviations: FRC, functional residual capacity; RV, residual volume; SE, standard error; OLO, olodaterol; TIO, tiotropium; FDC, fixed-dose combination.