title: Withdrawal of inhaled corticosteroids in people with COPD in primary care: a randomised controlled trial.
abstract: BACKGROUND
  Guidelines recommend inhaled corticosteroids (ICS) for patients with severe chronic obstructive pulmonary disease (COPD). Most COPD patients are managed in primary care and receive ICS long-term and irrespective of severity. The effect of withdrawing ICS from COPD patients in primary care is unknown.
  
  
  METHODS
  In a pragmatic randomised, double-blind, placebo-controlled trial in 31 practices, 260 COPD patients stopped their usual ICS (median duration of use 8 years) and were allocated to 500 mcg fluticasone propionate twice daily (n = 128), or placebo (n = 132). Follow-up assessments took place at three monthly intervals for a year at the patients' practice. Our primary outcome was COPD exacerbation frequency. Secondary outcomes were time to first COPD exacerbation, reported symptoms, peak expiratory flow rate and reliever inhaler use, and lung function and health related quality of life.
  
  
  RESULTS
  In patients randomised to placebo, COPD exacerbation risk over one year was RR: 1.11 (CI: 0.91-1.36). Patients taking placebo were more likely to return to their usual ICS following exacerbation, placebo: 61/128 (48%); fluticasone: 34/132 (26%), OR: 2.35 (CI: 1.38-4.05). Exacerbation risk whilst taking randomised treatment was significantly raised in the placebo group 1.48 (CI: 1.17-1.86). Patients taking placebo exacerbated earlier (median time to first exacerbation: placebo (days): 44 (CI: 29-59); fluticasone: 63 (CI: 53-74), log rank 3.81, P = 0.05) and reported increased wheeze. In a post-hoc analysis, patients with mild COPD taking placebo had increased exacerbation risk RR: 1.94 (CI: 1.20-3.14).
  
  
  CONCLUSIONS
  Withdrawal of long-term ICS in COPD patients in primary care increases risk of exacerbation shortens time to exacerbation and causes symptom deterioration. Patients with mild COPD may be at increased risk of exacerbation after withdrawal.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00440687.
authors.affiliation: Centre for Health Sciences, Queen Mary's School of Medicine and Dentistry, Barts and The London, 2 Newark Street, London, E1 2AT, UK. aklak.choudhury@btinternet.com
authors.forename: Aklak B
authors.initials: AB
authors.lastname: Choudhury
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Dawson
authors.forename: Hazel E
authors.initials: HE
authors.lastname: Kilvington
authors.forename: Sandra
authors.initials: S
authors.lastname: Eldridge
authors.forename: Wai-Yee
authors.initials: WY
authors.lastname: James
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
authors.forename: Gene S
authors.initials: GS
authors.lastname: Feder
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Griffiths
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D004311:Double-Blind Method; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D015990:Placebo Effect; D011320:Primary Health Care / Q000706:statistics & numerical data*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000453:epidemiology*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D016896:Treatment Outcome; D028761:Withholding Treatment / Q000706:statistics & numerical data*
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents