Roland Buhl1, Alberto de la Hoz2, Wenqiong Xue3, Dave Singh4, Gary T Ferguson5. 1. Pulmonary Department, Johannes Gutenberg Universitat Mainz, Mainz, Germany. Roland.Buhl@unimedizin-mainz.de. 2. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. 3. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. 4. Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK. 5. Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA.
Abstract
INTRODUCTION: The efficacy of tiotropium/olodaterol compared with tiotropium in patients with chronic obstructive pulmonary disease (COPD) has been demonstrated in a large clinical programme. Currently, randomised controlled trial (RCT) data on dual bronchodilation as first-line maintenance therapy are limited. In this post hoc analysis of pooled data from four RCTs, we compared the efficacy of tiotropium/olodaterol versus tiotropium as maintenance therapy in patients with COPD who were not receiving maintenance treatment with long-acting muscarinic antagonists (LAMAs), long-acting β2-agonists (LABAs) or inhaled corticosteroids (ICS) ("maintenance naïve") at study entry. METHODS: TONADO® 1/2 (52 weeks) and OTEMTO® 1/2 (12 weeks) were phase III RCTs in patients with COPD. TONADO 1/2 and OTEMTO 1/2 enrolled patients with post-bronchodilator forced expiratory volume in 1 s (FEV1) < 80% predicted (lower limit FEV1 ≥ 30% in OTEMTO 1/2 only). We examined the effect of tiotropium/olodaterol 5/5 µg versus tiotropium 5 µg on trough FEV1 response, St. George's Respiratory Questionnaire (SGRQ) total score and Transition Dyspnoea Index (TDI) focal score at 12 weeks in four pooled studies. RESULTS: The pooled analysis included 1078 maintenance-naïve patients. There were significant improvements with tiotropium/olodaterol versus tiotropium in trough FEV1 [0.056 L; 95% confidence interval (CI) 0.033, 0.079; P < 0.0001], SGRQ score (- 1.780; 95% CI - 3.126 to - 0.434; P = 0.0096) and TDI score (0.409; 95% CI 0.077, 0.741; P = 0.0158) at week 12. For patients receiving tiotropium/olodaterol, the odds of achieving a minimal clinically important difference from baseline in any of the analysed outcomes (FEV1 ≥ 0.1 L, SGRQ ≥ 4.0 points or TDI ≥ 1.0 point) were higher versus tiotropium. CONCLUSIONS: In patients who were maintenance naïve at baseline, treatment initiation with tiotropium/olodaterol resulted in greater improvements in lung function, health status and dyspnoea severity compared with tiotropium alone, without compromising patient safety. These results support the use of dual bronchodilation with tiotropium/olodaterol as first-line maintenance treatment in patients with COPD. TRIAL REGISTRATION: ClinicalTrials.gov: TONADO® 1 and 2 (NCT01431274 and NCT01431287, registered 8 September 2011) and OTEMTO® 1 and 2 (NCT01964352 and NCT02006732, registered 14 October 2013).
INTRODUCTION: The efficacy of tiotropium/olodaterol compared with tiotropium in patients with chronic obstructive pulmonary disease (COPD) has been demonstrated in a large clinical programme. Currently, randomised controlled trial (RCT) data on dual bronchodilation as first-line maintenance therapy are limited. In this post hoc analysis of pooled data from four RCTs, we compared the efficacy of tiotropium/olodaterol versus tiotropium as maintenance therapy in patients with COPD who were not receiving maintenance treatment with long-acting muscarinic antagonists (LAMAs), long-acting β2-agonists (LABAs) or inhaled corticosteroids (ICS) ("maintenance naïve") at study entry. METHODS: TONADO® 1/2 (52 weeks) and OTEMTO® 1/2 (12 weeks) were phase III RCTs in patients with COPD. TONADO 1/2 and OTEMTO 1/2 enrolled patients with post-bronchodilator forced expiratory volume in 1 s (FEV1) < 80% predicted (lower limit FEV1 ≥ 30% in OTEMTO 1/2 only). We examined the effect of tiotropium/olodaterol 5/5 µg versus tiotropium 5 µg on trough FEV1 response, St. George's Respiratory Questionnaire (SGRQ) total score and Transition Dyspnoea Index (TDI) focal score at 12 weeks in four pooled studies. RESULTS: The pooled analysis included 1078 maintenance-naïve patients. There were significant improvements with tiotropium/olodaterol versus tiotropium in trough FEV1 [0.056 L; 95% confidence interval (CI) 0.033, 0.079; P < 0.0001], SGRQ score (- 1.780; 95% CI - 3.126 to - 0.434; P = 0.0096) and TDI score (0.409; 95% CI 0.077, 0.741; P = 0.0158) at week 12. For patients receiving tiotropium/olodaterol, the odds of achieving a minimal clinically important difference from baseline in any of the analysed outcomes (FEV1 ≥ 0.1 L, SGRQ ≥ 4.0 points or TDI ≥ 1.0 point) were higher versus tiotropium. CONCLUSIONS: In patients who were maintenance naïve at baseline, treatment initiation with tiotropium/olodaterol resulted in greater improvements in lung function, health status and dyspnoea severity compared with tiotropium alone, without compromising patient safety. These results support the use of dual bronchodilation with tiotropium/olodaterol as first-line maintenance treatment in patients with COPD. TRIAL REGISTRATION: ClinicalTrials.gov: TONADO® 1 and 2 (NCT01431274 and NCT01431287, registered 8 September 2011) and OTEMTO® 1 and 2 (NCT01964352 and NCT02006732, registered 14 October 2013).
Authors: Donald A Mahler; Andrea Ludwig-Sengpiel; Gary T Ferguson; Alberto de la Hoz; John Ritz; Asif Shaikh; Henrik Watz Journal: Int J Chron Obstruct Pulmon Dis Date: 2021-08-28