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Multicenter Randomized Controlled Trial of Withdrawal of Inhaled Corticosteroids in Cystic Fibrosis

Department of Paediatric Respiratory Medicine and Clinical Trials & Evaluation Unit, Royal Brompton Hospital, London; National Heart & Lung Institute, Imperial College London, London; and Adult Cystic Fibrosis Unit, Belfast City Hospital, Belfast, United Kingdom

Correspondence and requests for reprints should be addressed to Ian M. Balfour-Lynn, M.D., F.R.P.C.H., Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Trust, Sydney Street, London SW3 6NP, UK. E-mail: i.balfourlynn{at}ic.ac.uk

Rationale: 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.

Objectives: 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 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.

Measurements and Main 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.

Key Words: antiinflammatory therapy • inhaled corticosteroids • lung diseases

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