Benefits of tiotropium/olodaterol compared with tiotropium in patients receiving COPD LAMA at baseline: pooled analysis of 4 clinical trials

Background: TONADO and OTEMTO were large, randomised, double-blind, Phase III trials that demonstrated the efficacy of tiotropium/olodaterol (T/O) compared with tiotropium (tio) in COPD.

Aim: We pooled data from TONADO and OTEMTO to investigate the effect on symptoms and lung function of stepping up treatment from tio to T/O in patients who received only tio at baseline.

Methods: TONADO 1 + 2 (NCT01431274/NCT01431287) were 52-week studies and OTEMTO 1 + 2 (NCT01964352/NCT02006732) were 12-week studies in patients with COPD with FEV₁ < 80% predicted in TONADO and ≥ 30% and < 80% predicted in OTEMTO. In this post hoc analysis, we examined the treatment differences between T/O 5/5 µg and tio 5 µg at 12 weeks in patients who received LAMA monotherapy at baseline. 98% of patients treated with LAMA received tio.

Results: At Week 12, T/O increased trough FEV₁ from baseline compared with tio (0.074 L; 95% CI 0.033, 0.115; [Table 1]). Improvements with T/O versus tio were seen in SGRQ total score (− 2.68; 95% CI − 5.06, − 0.29) and TDI score (1.15; 95% CI 0.56, 1.73). There was a greater likelihood of being a TDI responder and a trend towards a greater likelihood of being an SGRQ responder with T/O compared with tio.

Table 1 Pooled data from TONADO and OTEMTO showing treatment differences in trough FEV₁, SGRQ total score, TDI score and responder analyses after 12 weeks.

	n, T/O / tio	T/O vs. tio mean difference (95% CI)	P value	% responders, T/O/tio	T/O vs. tio, responder analysis odds ratio (95% CI)	p value
An SGRQ responder is defined as ≥ 4-unit improvement of SGRQ total score from baseline; a TDI responder is defined as ≥ 1-unit improvement of TDI score from baseline. Abbreviations: CI, confidence interval; FEV1, forced expiratory volume in 1 second; NA, not applicable; SRGQ, St. Georgeʼs Respiratory Questionnaire; T/O, tiotropium/olodaterol; TDI, Transition Dyspnoea Index; tio, tiotropium.
Trough FEV1, L	144/147	0.074 (0.033, 0.115)	0.0004		NA
SGRQ total score	141/142	− 2.68 (− 5.06, − 0.29)	0.0280	57.4/47.9	1.49 (0.93, 2.40)	0.0980
TDI score	140/143	1.15 (0.56, 1.73)	0.0001	57.1/31.5	2.81 (1.71, 4.60)	< 0.0001

Conclusions: In patients with COPD, optimising lung function by stepping up to T/O from tio led to significant improvements in lung function, health status and breathlessness.