Effect of Fixed-Dose Tiotropium/olodaterol Combined Therapy on Exercise-Related Outcome Measures in Individuals with Chronic Obstructive Pulmonary Disease: a Systematic Review and Meta-Analysis.

INTRODUCTION/OBJECTIVES:This systematic review aimed to summarize the evidence on the effect of the fixed-dose combination of tiotropium/olodaterol (Tio/Olo 5/5 μg FDC) on exercise-related outcome measures. METHODS:We included randomized clinical trials (RCTs) from four databases that investigated the effectiveness of Tio/Olo 5/5 μg FDC on exercise tolerance, breathlessness, lung function, and physical activity from inception to October 2024. RESULTS:Findings from eight RCTs indicated that Tio/Olo 5/5 μg FDC was superior to Tio 5 μg or placebo for the following outcomes: exercise tolerance [Tio 5 μg: 3 RCTs, mean difference (MD) = 16.6 m, 95% CI: 5.2-28.1, p < 0.001], exercise endurance time [Placebo: 2 RCTs, SMD = 0.29, 95% CI: 0.19-0.39, p = p < 0.001], inspiratory capacity [Tio 5 μg: 3 RCTs, MD = 0.13 L, 95% CI: 0.07-0.19, p < 0.001], and forced expiratory volume in 1 second (FEV1) [Tio 5 μg: 4 RCTs, MD = 0.12 L, 95% CI: 0.11-0.14, p < 0.001; Placebo: 2 RCTs, MD = 0.33 L, 95% CI: 0.3-0.35, p < 0.001], with no effect on physical activity levels. CONCLUSION:Tio/Olo 5/5 μg FDC compared to Tio 5 μg or placebo may improve exercise tolerance and lung function, but not physical activity levels in COPD. PROTOCOL REGISTRATION:The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): number CRD42024598553.