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

Respirology. 2016 Jan;21(1):119-27. doi: 10.1111/resp.12646. Epub 2015 Sep 23.

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.

Keywords: East Asia; budesonide/formoterol; chronic obstructive pulmonary disease; tiotropium.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asia, Eastern
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • Budesonide, Formoterol Fumarate Drug Combination* / administration & dosage
  • Budesonide, Formoterol Fumarate Drug Combination* / adverse effects
  • Drug Administration Schedule
  • Drug Monitoring / methods
  • Drug Therapy, Combination / methods
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / psychology
  • Quality of Life*
  • Severity of Illness Index
  • Symptom Flare Up
  • Tiotropium Bromide* / administration & dosage
  • Tiotropium Bromide* / adverse effects
  • Treatment Outcome

Substances

  • Bronchodilator Agents
  • Budesonide, Formoterol Fumarate Drug Combination
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01397890