Effects of tiotropium + olodaterol versus tiotropium or placebo by COPD disease severity and previous treatment history in the OTEMTO® studies

Abstract

Background: As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest. OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease. Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.

Methods: Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline. Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George's Respiratory Questionnaire (SGRQ) total score. Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.

Results: In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy. Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup. Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.

Conclusions: These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.

Trial registration: ClinicalTrials.gov: NCT01964352 and NCT02006732 .

Keywords: COPD; Long-acting bronchodilator; Olodaterol; Severity; Tiotropium; Treatment history.

Figures

Fig. 1

Patient disposition in OTEMTO® 1 and 2 (combined data). a1623 patients were randomised; 1 patient was entered twice but counted only once in the treated set

Fig. 2

Adjusted mean trough FEV1 responses at 12 weeks in patients with GOLD 2 and 3 disease. FEV1: forced expiratory volume in 1 s; GOLD: Global initiative for chronic Obstructive Lung Disease; SE: standard error; T: tiotropium; O: olodaterol

Fig. 3

Adjusted mean SGRQ total score at 12 weeks in patients with GOLD 2 and 3 disease. SGRQ: St George’s Respiratory Questionnaire; GOLD: Global initiative for chronic Obstructive Lung Disease; SE: standard error; T: tiotropium; O: olodaterol

Fig. 4

(a) FEV1 AUC0–3 and trough FEV1 responses, (b) SGRQ total score and (c) TDI focal score, all at 12 weeks: treatment comparisons for T + O 5/5 μg versus T 5 μg and versus placebo in patients with GOLD 2 and 3 disease. FEV1: forced expiratory volume in 1 s; AUC0–3: area under the curve from 0–3 h; SGRQ: St George’s Respiratory Questionnaire; TDI: Transition Dyspnoea Index; T: tiotropium; O: olodaterol; GOLD: Global initiative for chronic Obstructive Lung Disease; CI: confidence interval

Fig. 5

(a) FEV1 AUC0–3 and trough FEV1 responses, (b) SGRQ total score and (c) TDI focal score, all at 12 weeks: treatment comparisons for T + O 5/5 μg versus T 5 μg and versus placebo in patients with GOLD A–D disease. FEV1: forced expiratory volume in 1 s; AUC0–3: area under the curve from 0–3 h; SGRQ: St George’s Respiratory Questionnaire; TDI: Transition Dyspnoea Index; T: tiotropium; O: olodaterol; GOLD: Global initiative for chronic Obstructive Lung Disease; CI: confidence interval

Fig. 6

(a) FEV1 AUC0–3 and trough FEV1 responses, (b) SGRQ total score and (c) TDI focal score: treatment comparisons at 12 weeks for T + O 5/5 μg versus T 5 μg and versus placebo in patients who were treatment naive/not treatment naive at baseline. FEV1: forced expiratory volume in 1 s; AUC0–3: area under the curve from 0–3 h; SGRQ: St George’s Respiratory Questionnaire; TDI: Transition Dyspnoea Index; T: tiotropium; O: olodaterol; CI: confidence interval

Fig. 7

(a) FEV1 AUC0–3 and trough FEV1 responses, (b) SGRQ total score and (c) TDI focal score: treatment comparisons at 12 weeks for T + O 5/5 μg versus T 5 μg and versus placebo in patients who were receiving/ not receiving ICS treatment at baseline. FEV1: forced expiratory volume in 1 s; AUC0–3: area under the curve from 0–3 h; SGRQ: St George’s Respiratory Questionnaire; TDI: Transition Dyspnoea Index; T: tiotropium; O: olodaterol; ICS: inhaled corticosteroids; CI: confidence interval