title: Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma.
abstract: OBJECTIVE
  To investigate the relative efficacy of ciclesonide and fluticasone propionate (FP) administered at comparable microgram doses in maintaining asthma control in patients with moderate-to-severe persistent asthma.
  
  
  METHODS
  This randomized, open-label, parallel-group study enrolled patients aged 12-75 years with a 6-month history of bronchial asthma. To enter a 2-week run-in period, patients had to have received FP 500-1000 microg/day or equivalent at a stable dose for 4 weeks and have a forced expiratory volume in 1s (FEV 1) 80% of predicted. To enter the treatment period, patients had to have the following during run-in: FEV 1 80% of predicted; reversibility of Delta FEV 1 12% after 200-400 microg salbutamol; and 1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 microg (ex-actuator) or twice-daily FP 330 microg (ex-actuator) for 6 months. Efficacy was assessed by lung function, asthma exacerbations, asthma symptoms and rescue medication use. Patients completed the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Adverse events (AEs), including local oropharyngeal AEs, were recorded.
  
  
  RESULTS
  528 patients were randomized (ciclesonide, n=255; FP, n=273). In both groups, FEV 1 was maintained from baseline to study end (mean increase: ciclesonide 11 mL, FP 24 mL; intention-to-treat [ITT] analysis). The least squares mean+/-standard error of the mean for the treatment difference was -13+/-29 (95% confidence interval [CI]: -70, 44) in the ITT analysis and -27+/-34 (95% CI: -93, 40) in the per-protocol (PP) analysis, demonstrating non-inferiority of ciclesonide to FP. Morning, evening and site-measured PEF improved significantly with both treatments (ITT and PP analyses: p<0.05). Six patients receiving ciclesonide and seven receiving FP (ITT analysis) experienced an asthma exacerbation requiring treatment with oral corticosteroids. Both treatments significantly decreased asthma symptom score sum (ITT and PP analyses: p0.0001) and rescue medication use (ITT and PP analyses: p<0.05), with no significant difference between treatments. Both treatments significantly improved overall AQLQ(S) score (ITT and PP analyses: p<0.05). Significantly more patients experienced candidiasis and dysphonia with FP compared with ciclesonide (p=0.0023).
  
  
  CONCLUSIONS
  Ciclesonide 320 microg and FP 330 microg administered twice daily over 6 months provided similar efficacy in patients with moderate or severe persistent asthma previously well-controlled by high doses of ICS at baseline. Ciclesonide was associated with fewer local AEs than FP.
authors.affiliation: Division of Pulmonology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, PO Box 34560, Groote Schuur 7937, Cape Town, South Africa. Eric.Bateman@uct.ac.za
authors.forename: E D
authors.initials: ED
authors.lastname: Bateman
authors.forename: A E
authors.initials: AE
authors.lastname: Linnhof
authors.forename: L
authors.initials: L
authors.lastname: Homik
authors.forename: U
authors.initials: U
authors.lastname: Freudensprung
authors.forename: L
authors.initials: L
authors.lastname: Smau
authors.forename: R
authors.initials: R
authors.lastname: Engelstätter
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011282:Pregnenediones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D011282:Pregnenediones; D000068298:Fluticasone; C120481:ciclesonide