Rationale The once-daily combination of tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β2-agonist, has demonstrated efficacy and safety in COPD. Two large clinical studies (TONADO®1 + 2) have also demonstrated the benefits of T/O compared to the monocomponents in patients with moderate to very severe COPD. This post hoc analysis investigated whether T/O is more effective than T at delaying clinically significant events in patients with GOLD stage B COPD.
Methods A total of 5162 patients were randomised to O 5 µg, T 2.5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg (delivered via Respimat® inhaler) in two 52-week, parallel-group, double-blind studies (NCT01431274; NCT01431287). In this post hoc analysis of the combined TONADO® data, clinical deterioration was defined according to a composite end point: time to first decrease in trough forced expiratory volume in 1 second (FEV1) from baseline of ≥100 mL; increase in St George’s Respiratory Questionnaire (SGRQ) total score from baseline of ≥4 units; severe (hospitalised) exacerbation; or death. Only patients classified as GOLD stage B were included. Data are presented for comparisons of the licensed doses of T 5 µg and T/O 5/5 µg.
Results 306 and 310 patients were included in this analysis in the T 5 µg and T/O 5/5 µg treatment groups, respectively. Time to clinical deterioration was significantly longer with T/O 5/5 µg than T 5 µg (25th percentile 128 versus 85 days; HR 0.650; 95% CI: 0.524, 0.805; p < 0.0001) (Figure). Times to trough FEV1 decline and SGRQ increase were significantly longer with T/O 5/5 µg than T 5 µg (226 versus 91 days and 369 versus 175 days, respectively). 25th percentiles for time to severe exacerbation and time to death were not estimable due to low event rates.
Conclusions In the TONADO® studies, T/O increased time to clinical deterioration compared to T alone in patients with GOLD stage B disease. This suggests that, in this patient population, T/O is more effective than T in preventing these significant events. Further studies are warranted to prospectively study this effect.