Rationale The lung-function efficacy, symptomatic benefits and safety of combined tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β2-agonist, for the treatment of COPD, was established in the year-long TONADO® studies (NCT01431274; NCT01431287). It is unknown if these benefits of T/O translate into a reduction in COPD exacerbation rate.
Methods Two replicate, randomised, double-blind, parallel-group trials assessed T/O 2.5/5 μg and T/O 5/5 μg compared to the monocomponents T 5 μg, T 2.5 μg and O 5 µg (all delivered via Respimat® inhaler) in patients with moderate to very severe COPD. Primary end points included lung function (forced expiratory volume in 1 second [FEV1] area under the curve from 0–3 hours response, trough FEV1 response) and quality of life (SGRQ). Analysis of the number of exacerbations and time to exacerbation was pre-specified using data from the combined TONADO® studies. We present data from the T/O and T treatment arms.
Results 4124 patients were evaluable for the T/O and T treatment arms. Moderate or severe exacerbations occurred in 27.7% of patients with T/O 5/5 μg, 25.8% of patients with T/O 2.5/5 μg, 28.8% with T 5 μg and 29.6% with T 2.5 μg. Severe exacerbations occurred in 5.9% of patients receiving T/O 5/5 μg, 4.5% receiving T/O 2.5/5 μg, 4.5% receiving T 5 μg and 5.2% receiving T 2.5 μg. The treatment comparisons for any exacerbation and moderate/severe exacerbations were generally consistent between the two studies, except for a higher number of severe exacerbations with T/O 5/5 μg in TONADO® 1 only (Table).
Conclusions Although there were fewer exacerbations overall with T/O 2.5/5 µg or 5/5 µg compared to T 2.5 µg or 5 µg, and a numerically longer time to first moderate/severe exacerbation, the TONADO® studies did not show a significant difference in the hazard ratios for time to exacerbation end points. These findings are partially attributable to a higher number of severe exacerbations with T/O 5/5 µg in TONADO® 1. TONADO® was not designed for formal comparison of exacerbations with T/O versus T; however, a study powered to assess this is ongoing.
Funding Boehringer Ingelheim.
Please refer to page A273 for declarations of interest in relation to abstract P296.