Efficacy of Tiotropium + Olodaterol in Patients with Chronic Obstructive Pulmonary Disease by Initial Disease Severity and Treatment Intensity: A Post Hoc Analysis

Abstract

Introduction: The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD). Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents. This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.

Methods: 5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat(®) inhaler). Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline). Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.

Results: Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05). FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.

Conclusions: Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment. Improvements from baseline in lung function were generally greater in patients with less severe disease.

Funding: Boehringer Ingelheim.

Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.

Figures

Fig. 1

Study design (Study 1237.5: NCT01431274; Study 1237.6: NCT01431287). R randomization, FDC fixed-dose combination, QD once daily

Fig. 2

Key inclusion and exclusion criteria. COPD chronic obstructive pulmonary disease, GOLD Global initiative for chronic Obstructive Lung Disease, FEV1 forced expiratory volume in 1 s

Fig. 3

Adjusted mean FEV1 AUC0–3 responses at 24 weeks; pooled data from TONADO-1 and -2. a Patients without prior LAMA or LABA use; b patients with prior LAMA or LABA use. FEV1 forced expiratory volume in 1 s, AUC0–3 area under the curve from 0 to 3 h, LAMA long-acting muscarinic antagonist, LABA long-acting β2-agonist, SE standard error, O olodaterol, T tiotropium, GOLD Global initiative for chronic Obstructive Lung Disease

Fig. 4

Adjusted mean trough FEV1 responses at 24 weeks; pooled data from TONADO-1 and -2. a Patients without prior LAMA or LABA use; b patients with prior LAMA or LABA use. FEV1 forced expiratory volume in 1 s, LAMA long-acting muscarinic antagonist, LABA long-acting β2-agonist, SE standard error, O olodaterol, T tiotropium, GOLD Global initiative for chronic Obstructive Lung Disease

Fig. 5

Forest plots for FEV1 AUC0–3 responses at 24 weeks. a Tiotropium + olodaterol 5/5 µg versus olodaterol 5 µg; b tiotropium + olodaterol 5/5 µg versus tiotropium 5 µg. FEV1 forced expiratory volume in 1 s, AUC0–3 area under the curve from 0 to 3 h, ICS inhaled corticosteroid

Fig. 6

Forest plots for trough FEV1 responses at 24 weeks. a Tiotropium + olodaterol 5/5 µg versus olodaterol 5 µg; b tiotropium + olodaterol 5/5 µg versus tiotropium 5 µg. FEV1 forced expiratory volume in 1 s, ICS inhaled corticosteroid