title: Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: A randomized, multicentre study in East Asia.
abstract: 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.
  
  
  BACKGROUND
  NCT01397890 at Clinicaltrials.gov.
authors.affiliation: 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.
authors.forename: Sang-Do
authors.initials: SD
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Can-Mao
authors.initials: CM
authors.lastname: Xie
authors.affiliation: Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Indonesia, Persahabatan Hospital, Jakarta, Indonesia.
authors.forename: Faisal
authors.initials: F
authors.lastname: Yunus
authors.affiliation: AstraZeneca, Osaka, Japan.
authors.forename: Yohji
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: AstraZeneca, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ling
authors.affiliation: Department of Medicine and Geriatrics, Princess Margaret Hospital, Kowloon, Hong Kong, China.
authors.forename: Wai-cho
authors.initials: WC
authors.lastname: Yu
authors.affiliation: Pulmonary and Critical Care Unit, Department of Medicine, Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Sumalee
authors.initials: S
authors.lastname: Kiatboonsri
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D000069502:Budesonide, Formoterol Fumarate Drug Combination / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D005202:Asia, Eastern; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D011788:Quality of Life; D012720:Severity of Illness Index; D000067251:Symptom Flare Up; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D000069447:Tiotropium Bromide
keywords: East Asia; budesonide/formoterol; chronic obstructive pulmonary disease; tiotropium