Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs fluticasone 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma.
OBJECTIVE
There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-moderate persistent asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life.


METHODS
Nineteen mild-to-moderate asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits.


RESULTS
There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline.


CONCLUSIONS
There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations.
Lee
Daniel K C
DK
Asthma & Allergy Research Group, Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Dundee DDI 9SY, Scotland, UK.
Haggart
Kay
K
Currie
Graeme P
GP
Bates
Caroline E
CE
Lipworth
Brian J
BJ
D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D001985:Bronchial Provocation Tests / Q000379:methods; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D011282:Pregnenediones / Q000008:administration & dosage* / Q000737:chemistry; D014797:Vital Capacity / Q000187:drug effects
D000730:Androstadienes; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; D011282:Pregnenediones; D016210:Methacholine Chloride; D000068298:Fluticasone; C120481:ciclesonide