Sang-Do Lee1, Can-Mao Xie2, Faisal Yunus3, Yohji Itoh4, Xia Ling5, Wai-cho Yu6, Sumalee Kiatboonsri7. 1. Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 2. Department of Pulmonary and Critical Care Medicine, 1st Hospital of Sun Yat-sen University, Institute of Respiratory Disease of Sun Yat-sen University, Guangzhou, Guangdong, China. 3. Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Indonesia, Persahabatan Hospital, Jakarta, Indonesia. 4. AstraZeneca, Osaka, Japan. 5. AstraZeneca, Shanghai, China. 6. Department of Medicine and Geriatrics, Princess Margaret Hospital, Kowloon, Hong Kong, China. 7. Pulmonary and Critical Care Unit, Department of Medicine, Ramathibodi Hospital, Bangkok, Thailand.
Abstract
BACKGROUND AND OBJECTIVE: Triple combination therapy with tiotropium plus budesonide/formoterol has improved lung function and reduced exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) in Western countries, but no such data exist for East Asian patients. This study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium compared with tiotropium alone in East Asian patients with severe/very severe COPD. METHODS: This 12-week, randomized, parallel-group, multicentre, open-label study was conducted in East Asia. After a 14-day run-in period during which patients received tiotropium 18 μg once daily, patients were randomized to tiotropium (18 μg once daily) + budesonide/formoterol (160/4.5 μg 2 inhalations twice daily) or tiotropium alone (18 μg once daily). The primary endpoint was change from baseline in pre-dose forced expiratory volume in 1 s (FEV1 ) to the mean of values measured at Weeks 1, 6 and 12. RESULTS:Pre-dose FEV1 significantly increased from baseline with tiotropium plus budesonide/formoterol (n = 287) versus tiotropium alone (n = 291) (5.0% vs 0.6%; treatment difference: 4.4% (95% CI: 1.9-6.9), P = 0.0004). Triple therapy also reduced the COPD exacerbation rate by 40.7% (P = 0.0032) and prolonged time to first exacerbation (38.6% risk reduction, P = 0.0167) versus tiotropium alone and markedly improved health-related quality of life (HRQoL), measured using the St George's Respiratory Questionnaire. Incidence of adverse events was 26% for both groups. CONCLUSIONS: In East Asian patients with severe/very severe COPD, adding budesonide/formoterol to tiotropium was associated with significant improvements in FEV1 and HRQoL and lower COPD exacerbation rates. Treatment was generally well tolerated. CLINICAL TRIAL REGISTRATION: NCT01397890 at Clinicaltrials.gov.
RCT Entities:
BACKGROUND AND OBJECTIVE: Triple combination therapy with tiotropium plus budesonide/formoterol has improved lung function and reduced exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) in Western countries, but no such data exist for East Asian patients. This study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium compared with tiotropium alone in East Asian patients with severe/very severe COPD. METHODS: This 12-week, randomized, parallel-group, multicentre, open-label study was conducted in East Asia. After a 14-day run-in period during which patients received tiotropium 18 μg once daily, patients were randomized to tiotropium (18 μg once daily) + budesonide/formoterol (160/4.5 μg 2 inhalations twice daily) or tiotropium alone (18 μg once daily). The primary endpoint was change from baseline in pre-dose forced expiratory volume in 1 s (FEV1 ) to the mean of values measured at Weeks 1, 6 and 12. RESULTS: Pre-dose FEV1 significantly increased from baseline with tiotropium plus budesonide/formoterol (n = 287) versus tiotropium alone (n = 291) (5.0% vs 0.6%; treatment difference: 4.4% (95% CI: 1.9-6.9), P = 0.0004). Triple therapy also reduced the COPD exacerbation rate by 40.7% (P = 0.0032) and prolonged time to first exacerbation (38.6% risk reduction, P = 0.0167) versus tiotropium alone and markedly improved health-related quality of life (HRQoL), measured using the St George's Respiratory Questionnaire. Incidence of adverse events was 26% for both groups. CONCLUSIONS: In East Asian patients with severe/very severe COPD, adding budesonide/formoterol to tiotropium was associated with significant improvements in FEV1 and HRQoL and lower COPD exacerbation rates. Treatment was generally well tolerated. CLINICAL TRIAL REGISTRATION: NCT01397890 at Clinicaltrials.gov.
Authors: Jinping Zheng; Simonetta Baldi; Li Zhao; Huiping Li; Kwan-Ho Lee; Dave Singh; Alberto Papi; Frédérique Grapin; Alessandro Guasconi; George Georges Journal: Respir Res Date: 2021-03-23
Authors: Arnaud Bourdin; Nicolas Molinari; Gary T Ferguson; Barinder Singh; Mohd Kashif Siddiqui; Ulf Holmgren; Mario Ouwens; Martin Jenkins; Enrico De Nigris Journal: Adv Ther Date: 2021-04-30 Impact factor: 3.845