Benefits of Tiotropium/Olodaterol Compared with Tiotropium in Patients with COPD Receiving only LAMA at Baseline: Pooled Analysis of the TONADO® and OTEMTO® Studies

Roland Buhl, Dave Singh, Alberto de la Hoz, Wenqiong Xue, Gary T Ferguson, Roland Buhl, Dave Singh, Alberto de la Hoz, Wenqiong Xue, Gary T Ferguson

Abstract

Introduction: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report recommends long-acting muscarinic antagonists (LAMA) or long-acting β2-agonists (LABA) as first-line treatment for chronic obstructive pulmonary disease (COPD), but many patients remain symptomatic on monotherapy and escalation to dual-bronchodilator therapy may be warranted.

Methods: TONADO® 1&2 and OTEMTO® 1&2 assessed lung function and patient-reported outcomes in patients with moderate-to-severe (OTEMTO) or moderate-to-very-severe (TONADO) COPD. This pooled post hoc analysis included patients treated with LAMA monotherapy at baseline who were randomised to receive either 5 µg tiotropium (LAMA) or 5/5 µg tiotropium/olodaterol (LAMA/LABA). We assessed changes from baseline and responder rates for trough forced expiratory volume in 1 s (FEV1), St. George's Respiratory Questionnaire (SGRQ) and the Transition Dyspnoea Index (TDI).

Results: Overall, 151 patients received tiotropium; 148 received tiotropium/olodaterol. Mean differences from baseline with tiotropium/olodaterol versus tiotropium were + 0.074 l (95% confidence interval [CI] 0.033, 0.115; P = 0.0004) for trough FEV1, - 2.675 (95% CI - 5.060, - 0.291; P = 0.0280) for SGRQ and 1.148 (95% CI 0.564, 1.732; P = 0.0001) for TDI. Patients were more likely to respond when treated with tiotropium/olodaterol versus tiotropium for trough FEV1 (odds ratio [OR] 3.14, 95% CI 1.94, 5.06; P < 0.0001), SGRQ (OR 1.49, 95% CI 0.93, 2.40; P = 0.0980) and TDI (OR 2.81, 95% CI 1.71, 4.60; P < 0.0001). Minimum clinically important difference from baseline in any of the analysed outcomes (FEV1 ≥ 0.1 l, SGRQ ≥ 4.0 points or TDI ≥ 1.0 point) was more likely in patients treated with tiotropium/olodaterol versus tiotropium (OR 2.43, 95% CI 1.32, 4.51; P = 0.0046).

Conclusion: In patients with COPD receiving only LAMA monotherapy, treatment escalation to tiotropium/olodaterol resulted in statistically significant and clinically relevant improvements in lung function, health status and breathlessness. These results support early therapy optimisation to dual bronchodilation with tiotropium/olodaterol in patients receiving tiotropium alone.

Trial registration: TONADO® 1 was registered in the US National Library of Medicine on 9 September 2011 (Clinicaltrials.gov: NCT01431274). TONADO® 2 was registered in the US National Library of Medicine on 9 September 2011 (Clinicaltrials.gov: NCT01431287). OTEMTO® 1 was registered in the US National Library of Medicine on 17 October 2013 (Clinicaltrials.gov: NCT01964352). OTEMTO® 2 was registered in the US National Library of Medicine on 10 December 2013 (Clinicaltrials.gov: NCT02006732).

Keywords: Bronchodilator; FEV1; LAMA; OTEMTO; SGRQ; TDI; TONADO; Tiotropium/olodaterol.

Figures

Fig. 1
Fig. 1
FEV1 change from baseline at 12 weeks. The common baseline mean was calculated as 1.219 ± 0.029 l. *P = 0.0004 (P < 0.001). CI, confidence interval; FEV1, forced expiratory volume in 1 s; SE, standard error; T/O, tiotropium/olodaterol; Tio, tiotropium
Fig. 2
Fig. 2
SGRQ change from baseline at 12 weeks. Common baseline mean for SGRQ was 38.74 ± 0.972 points. *P = 0.0280 (P < 0.05). CI, confidence interval; SE, standard error; SGRQ, St. George’s Respiratory Questionnaire; T/O, tiotropium/olodaterol; Tio, tiotropium
Fig. 3
Fig. 3
TDI change from baseline at 12 weeks. At baseline, patients from the TONADO and OTEMTO trials showed a combined baseline mean of 7.138 ± 0.117 points. *P = 0.0001. CI, confidence interval; SE, standard error; T/O, tiotropium/olodaterol; TDI, Transition Dyspnoea Index; Tio, tiotropium
Fig. 4
Fig. 4
Assessed responder rates after 12 weeks. *MCID in at least one of the assessed outcomes (FEV1 ≥ 0.1 l, SGRQ ≥ 4.0 points or TDI ≥ 1.0 point). CI, confidence interval; FEV1, forced expiratory volume in 1 s; MCID, minimum clinically important difference; SGRQ, St. George’s Respiratory Questionnaire; T/O, tiotropium/olodaterol; TDI, Transition Dyspnoea Index; Tio, tiotropium
Fig. 5
Fig. 5
Subgroup analysis of responder rates by GOLD stage. CI, confidence interval; GOLD, Global Initiative for Chronic Obstructive Lung Disease; T/O, tiotropium/olodaterol; TDI, Transition Dyspnoea Index; Tio, tiotropium

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Source: PubMed

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