Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis.
BACKGROUND
Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.


OBJECTIVE
To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.


METHODS
Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.


RESULTS
Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo.


CONCLUSIONS
In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.
Balfour-Lynn
Ian M
IM
Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Trust, and National Heart & Lung Institute, Imperial College London, SW3 6NP, UK. i.balfourlynn@ic.ac.uk
Lees
Belinda
B
Hall
Pippa
P
Phillips
Gillian
G
Khan
Mohammed
M
Flather
Marcus
M
Elborn
J Stuart
JS
D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D000068298:Fluticasone; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012449:Safety; D028761:Withholding Treatment
D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D010919:Placebos; D000068298:Fluticasone