Inhaled fluticasone at different doses for chronic asthma

Abstract

Background: Inhaled fluticasone propionate (FP) is a high potency inhaled corticosteroid used in the treatment of asthma.

Objectives: 1. To assess the efficacy and safety outcomes in studies that compared inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma. 2. To test for the presence of a dose response effect.

Search strategy: We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).

Selection criteria: Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.

Data collection and analysis: One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.

Main results: 20 studies (>6000 patients) met the inclusion criteria. Methodological quality was high. In non-oral steroid treated asthmatics with mild-moderate disease, a dose response effect was present for morning PEF; when comparing low doses (200 vs 100 mcg/d) Weighted Mean Difference (WMD) 6 L/min, 95% Confidence Interval (CI) 1, 10 L/min; medium-low dose (400-500 vs 100 mcg/d), WMD 8 L/min, 95%CI 1,15 L/min); and high vs low dose (800-1000 vs 50-100 mcg/d), WMD 22 L/min 95% CI 15,29 L/min). There was no dose response in symptoms or rescue beta2 agonist use. Hoarseness and oral Candidiasis was significantly higher with 800-1000 mcg/d than 50-100 mcg/d. In oral steroid dependent disease gain 2000 mcg/d had a greater effect than 1000-1500 mcg/d in likelihood of stopping prednisolone (Peto Odds Ratio 2.8, 95% CI 1.3, 6.3) and reduced daily prednisolone dose (WMD 2.0 mg/d, 95% CI 0.1, 4.0 mg/d).

Reviewer's conclusions: Effects of fluticasone are dose dependent but relatively small. Patients with mild to moderate disease achieve similar levels of asthma control on low doses of fluticasone (200 mcg/d or less) as they do on high doses (500 mcg/d or greater). In oral corticosteroid dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 mcg/d.