title: Withdrawal of inhaled glucocorticoids and exacerbations of COPD.
abstract: BACKGROUND
  Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored.
  
  
  METHODS
  In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored.
  
  
  RESULTS
  As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group.
  
  
  CONCLUSIONS
  In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Helgo
authors.initials: H
authors.lastname: Magnussen
authors.forename: Bernd
authors.initials: B
authors.lastname: Disse
authors.forename: Roberto
authors.initials: R
authors.lastname: Rodriguez-Roisin
authors.forename: Anne
authors.initials: A
authors.lastname: Kirsten
authors.forename: Henrik
authors.initials: H
authors.lastname: Watz
authors.forename: Kay
authors.initials: K
authors.lastname: Tetzlaff
authors.forename: Lesley
authors.initials: L
authors.lastname: Towse
authors.forename: Helen
authors.initials: H
authors.lastname: Finnigan
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D013147:Spirometry; D000069447:Tiotropium Bromide; D028761:Withholding Treatment
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000069447:Tiotropium Bromide