Jadwiga A Wedzicha1, Roland Buhl2, Dave Singh3, Claus F Vogelmeier4, Alberto de la Hoz5, Wenqiong Xue6, Antonio Anzueto7, Peter M A Calverley8. 1. Respiratory Division, National Heart and Lung Institute, Imperial College London, London, UK. j.wedzicha@imperial.ac.uk. 2. Johannes Gutenberg University Mainz, Mainz, Germany. 3. Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK. 4. Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps University of Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany. 5. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. 6. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. 7. Department of Pulmonary Medicine and Critical Care, University of Texas Health Sciences Center and South Texas Veterans Health Care System, San Antonio, TX, USA. 8. Clinical Science Centre, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Abstract
INTRODUCTION: Previous studies demonstrated that tiotropium/olodaterol reduced rates of exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this should be examined in a wider population. METHODS: This post hoc analysis pooled data from TONADO® 1 + 2 and DYNAGITO®, three 52-week, parallel-group, randomised, double-blind, phase III trials investigating patients with moderate-to-very severe COPD, with and without previous exacerbations, who received tiotropium/olodaterol 5/5 µg or tiotropium 5 µg. Subgroup analyses were conducted on patients stratified by exacerbation history, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 disease severity and baseline inhaled corticosteroid (ICS) use. RESULTS: In 9942 patients, tiotropium/olodaterol was associated with lower rates of moderate/severe exacerbations (0.68 vs. 0.77 per patient-year; rate ratio (RR) vs. tiotropium 0.89, 95% confidence interval (CI) 0.84, 0.95; P = 0.0003) and exacerbations requiring hospitalisation (0.11 vs. 0.13 per patient-year; RR 0.86, 95% CI 0.75, 0.99; P = 0.0380) versus tiotropium. Lower rates of moderate/severe exacerbations with tiotropium/olodaterol versus tiotropium were evident in patients with 0-1 moderate exacerbation in the previous year (0.54 vs. 0.60 per patient-year; RR 0.90, 95% CI 0.82, 0.98; P = 0.0187) and at least two moderate or at least one severe exacerbation(s) in the previous year (0.97 vs. 1.09 per patient-year; RR 0.89, 95% CI 0.82, 0.97; P = 0.0096). In patients with GOLD 2 and GOLD 3 COPD, moderate/severe exacerbation rates were lower with tiotropium/olodaterol versus tiotropium; GOLD 4 patients showed negligible difference between treatments. When evaluating patients by baseline ICS use, there was a significantly lower rate of moderate/severe exacerbations with tiotropium/olodaterol versus tiotropium in patients receiving ICS. CONCLUSIONS: Tiotropium/olodaterol decreased the rate of moderate/severe exacerbations and exacerbations leading to hospitalisation versus tiotropium. Results from this large, pooled, post hoc analysis support the use of dual bronchodilation with tiotropium/olodaterol in a broad range of patients, reflective of patients with COPD in clinical practice. TRIAL REGISTRATION: TONADO® 1 (ClinicalTrials.gov: NCT01431274); TONADO® 2 (ClinicalTrials.gov: NCT01431287); DYNAGITO® (ClinicalTrials.gov: NCT02296138). People with chronic obstructive pulmonary disease (COPD) may have times when their symptoms worsen, known as exacerbations. This may mean that they need to take additional medications, such as antibiotics or oral steroids. Studies have shown that a combination of two types of inhaled medicine-tiotropium and olodaterol-can help to reduce exacerbations in some people. To see if this is also the case across a larger and more diverse range of people, we combined the results from three studies (TONADO® 1 + 2 and DYNAGITO®) that looked at people who were taking tiotropium and olodaterol together and people who were taking tiotropium alone. We showed that, across a wide range of people, treatment with tiotropium/olodaterol was generally better at reducing exacerbations than tiotropium. Tiotropium/olodaterol also decreased the number of exacerbations that led to hospitalisation compared with tiotropium. Overall, our results support the use of combined tiotropium/olodaterol in people at different stages of COPD.
INTRODUCTION: Previous studies demonstrated that tiotropium/olodaterol reduced rates of exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this should be examined in a wider population. METHODS: This post hoc analysis pooled data from TONADO® 1 + 2 and DYNAGITO®, three 52-week, parallel-group, randomised, double-blind, phase III trials investigating patients with moderate-to-very severe COPD, with and without previous exacerbations, who received tiotropium/olodaterol 5/5 µg or tiotropium 5 µg. Subgroup analyses were conducted on patients stratified by exacerbation history, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 disease severity and baseline inhaled corticosteroid (ICS) use. RESULTS: In 9942 patients, tiotropium/olodaterol was associated with lower rates of moderate/severe exacerbations (0.68 vs. 0.77 per patient-year; rate ratio (RR) vs. tiotropium 0.89, 95% confidence interval (CI) 0.84, 0.95; P = 0.0003) and exacerbations requiring hospitalisation (0.11 vs. 0.13 per patient-year; RR 0.86, 95% CI 0.75, 0.99; P = 0.0380) versus tiotropium. Lower rates of moderate/severe exacerbations with tiotropium/olodaterol versus tiotropium were evident in patients with 0-1 moderate exacerbation in the previous year (0.54 vs. 0.60 per patient-year; RR 0.90, 95% CI 0.82, 0.98; P = 0.0187) and at least two moderate or at least one severe exacerbation(s) in the previous year (0.97 vs. 1.09 per patient-year; RR 0.89, 95% CI 0.82, 0.97; P = 0.0096). In patients with GOLD 2 and GOLD 3 COPD, moderate/severe exacerbation rates were lower with tiotropium/olodaterol versus tiotropium; GOLD 4 patients showed negligible difference between treatments. When evaluating patients by baseline ICS use, there was a significantly lower rate of moderate/severe exacerbations with tiotropium/olodaterol versus tiotropium in patients receiving ICS. CONCLUSIONS: Tiotropium/olodaterol decreased the rate of moderate/severe exacerbations and exacerbations leading to hospitalisation versus tiotropium. Results from this large, pooled, post hoc analysis support the use of dual bronchodilation with tiotropium/olodaterol in a broad range of patients, reflective of patients with COPD in clinical practice. TRIAL REGISTRATION: TONADO® 1 (ClinicalTrials.gov: NCT01431274); TONADO® 2 (ClinicalTrials.gov: NCT01431287); DYNAGITO® (ClinicalTrials.gov: NCT02296138). People with chronic obstructive pulmonary disease (COPD) may have times when their symptoms worsen, known as exacerbations. This may mean that they need to take additional medications, such as antibiotics or oral steroids. Studies have shown that a combination of two types of inhaled medicine-tiotropium and olodaterol-can help to reduce exacerbations in some people. To see if this is also the case across a larger and more diverse range of people, we combined the results from three studies (TONADO® 1 + 2 and DYNAGITO®) that looked at people who were taking tiotropium and olodaterol together and people who were taking tiotropium alone. We showed that, across a wide range of people, treatment with tiotropium/olodaterol was generally better at reducing exacerbations than tiotropium. Tiotropium/olodaterol also decreased the number of exacerbations that led to hospitalisation compared with tiotropium. Overall, our results support the use of combined tiotropium/olodaterol in people at different stages of COPD.
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
Authors: Peter M A Calverley; Alberto Papi; Clive Page; Paola Rogliani; Roberto W Dal Negro; Mario Cazzola; Arrigo F Cicero; Jadwiga A Wedzicha Journal: Int J Chron Obstruct Pulmon Dis Date: 2022-08-22