Analysis Of The Efficacy And Safety Of The Fixed-Dose Combination Of Tiotropium + Olodaterol In Patients With COPD By Previous Usage Of Inhaled Corticosteroids

Rationale: Tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β2-agonist (both administered once-daily), have been studied as a once-daily fixed-dose combination (FDC). Two Phase III studies have demonstrated that T+O FDC significantly improved lung function and symptoms over T and O monotherapy treatments in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).¹ During these studies, patients were allowed to continue existing treatment with inhaled corticosteroids (ICS); this analysis was conducted to determine the effects of study treatment on lung function in patients receiving or not receiving ICS as reported at baseline.

Methods: 5162 patients were randomized to treatment with O 5 µg, T 2.5 µg, T 5 µg, T+O 2.5/5 µg, or T+O 5/5 µg (Respimat^® inhaler) in two 52-week, double-blind, parallel-group studies. Primary efficacy end points were trough forced expiratory volume in 1 second (FEV₁) response (i.e. change from baseline), FEV₁ area under the curve from 0 – 3 hours (AUC0 – 3) response, and St. George's Respiratory Questionnaire (SGRQ) total score after 24 weeks. Pooled data are presented for the patient subgroups either using or not using ICS at baseline.

Results: In the overall population, all treatments resulted in clinically relevant improvements in lung function, with significant increases with both T+O doses over the individual components (p < 0.01).¹ These effects on lung function were observed irrespective of whether or not patients had reported concomitant use of ICS at baseline (see Table).

Conclusions: In patients with COPD, T+O 5/5 µg significantly improved lung function over T 5 µg and O 5 µg monotherapy, irrespective of whether patients had reported ICS use at baseline.

Tab. 1: Lung function responses at 24 weeks according to baseline ICS usage^a

		Trough FEV1, L	FEV 1 AUC 0 – 3, L
	n	Adjusted mean (SE) change	n	Adjusted mean (SE) change
ICS usage
	497	0.046 (0.009)	503	0.129 (0.009)
O 5
	471	0.084 (0.009)	476	0.142 (0.009)
T 2.5
	464	0.088 (0.009)	465	0.147 (0.009)
T 5
	489	0.114 (0.009) †#*	492	0.246 (0.009) †##**
T+O 2.5/5
	503	0.133 (0.009) †##**	505	0.260 (0.008) †##**
T+O 5/5
No ICS usage
	510 0.067 (0.009)		514	0.139 (0.009)
O 5
	533 0.062 (0.009)		537	0.132 (0.008)
T 2.5
	536	0.073 (0.009)	543	0.155 (0.008)
T 5
	511	0.122 (0.009) †##**	517	0.252 (0.008) †##**
T+O 2.5/5
	500 0.149 (0.009) †##**		503	0.263 (0.009) †##**
T+O 5/5
†p < 0.0001 vs. O 5; ##p < 0.0001 vs. T 2.5; **p < 0.001 vsT 5 SE, standard error a Patients were not recorded as receiving LAMA or LABA at baseline in this study

Reference

1. Buhl R et al. Eur Respir J 2014; 45(4):969 – 79.

Funding: Boehringer Ingelheim.