PURPOSE: To compare the safety and efficacy of the inhaled corticosteroids (ICS) ciclesonide (CIC) and fluticasone propionate (FP) in the management of persistent asthma in adult patients, as assessed by cortisol suppression and attenuation of airway hyperresponsiveness to methacholine.
METHODS: This double-blind, two-arm parallel group study included patients aged 18–70 years with persistent asthma and pretreated with ICS (200–1000μg/d BDP-CFC equivalents). After a 3-week baseline period (BDP-CFC 100μg bid only), patients were randomized to receive via HFA-MDI escalating low, medium, and high (L, M, H) doses (ex-actuator) of CIC (n=54) or FP (n=49), each during 3-week treatment periods (L=CIC 320μg qd or FP 220μg bid, M=CIC 320μg bid or FP 440μg bid, H=CIC 640μg bid or FP 880μg bid). Airway hyperresponsiveness (PC20FEV1 methacholine) and cortisol levels (serum and urine) were determined at baseline and after each treatment period.
RESULTS: Treatment with the three escalating doses of CIC produced no statistically significant change in the primary variable serum cortisol (measured as AUC(0–24h)/24h) or 24-h creatinine-adjusted urinary cortisol. In contrast, both measures of cortisol were significantly suppressed by M and H doses of FP (p=0.018 and p<0.0001 for serum). Superiority of CIC to FP was demonstrated for M and H doses. Regarding methacholine challenge, PC20FEV1 (doubling concentrations) for L, M, and H doses were 0.56, 0.96, 0.94 for CIC, and 0.25, 0.80, 1.16 for FP. There were no statistically significant differences in PC20 between CIC and FP. Adverse events were generally mild or moderate in intensity, and were slightly more frequent in patients treated with FP. Oropharyngeal candidiasis was confirmed in four FP patients, but only one CIC patient.
CONCLUSION: Across a range of doses, CIC and FP showed similar efficacy (as assessed by attenuation of airway hyperresponsiveness) but were significantly different in their effect on HPA-axis function.
CLINICAL IMPLICATIONS: This study confirmed the results of previous studies showing that ciclesonide has similar efficacy to FP at comparable doses but significantly less potential to induce systemic side effects.
DISCLOSURE: J. FitzGerald, University grant monies Funding received from Astra Zeneca, GSK, Novartis, Boerhinger Ingelheim paid directly to UBC held research accounts; Grant monies (from sources other than industry) Canadian Institutes for Health Research: Michael Smith Foundation for Health Research; Grant monies (from industry related sources) Astra Zeneca, GSK, Novartis, Boerhinger Ingelheim; Consultant fee, speaker bureau, advisory committee, etc. Lecture fees and consultant fees with the above named companies as well as the following Topigen, Inflazyme, Merck, Altana, Novartis; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Ciclesonide HFA-MDI is not approved for use in the United States. The study was sponsored by ALTANA Pharma AG, a member of the Nycomed Group.