Ciclesonide has minimal oropharyngeal side effects in the treatment of patients with moderate-to-severe asthma

Inhaled corticosteroids (ICSs) are first-line therapy for all severities of persistent asthma; however, oropharyngeal side effects may negatively impact their use. Ciclesonide (CIC, hydrofluoroalkane metered dose inhaler [HFA-MDI]) is an effective and novel ICS which has very low affinity for the glucocorticoid receptor in its native form, but very high affinity when transformed to its active metabolite by esterases in the lung. In this study, oropharyngeal side effects of CIC were examined in a Phase III trial to determine if the pharmacologic properties of the drug would result in a more desirable oropharyngeal safety profile as anticipated. In this multicenter, double-blind, randomized, placebo and active-controlled, parallel-group trial, patients (n=531) with ≥6 mo moderate-to-severe asthma (FEV 1 40%-65% of predicted) were randomized to receive CIC 160 μg bid (CIC320), CIC 320 μg bid (CIC640), fluticasone propionate 440 μg bid (FP880, chlorofluorocarbon MDI) or placebo (PBO) for 12 weeks (ex-actuator doses). Oropharyngeal effects were monitored throughout the study. Suspected oral fungal infections were verified by culture in a central laboratory. The incidence of oropharyngeal adverse events for CIC was similar to PBO and less than with FP: oral candidiasis (CIC320 0.8%, CIC640 0.0%, FP880 11.6%, PBO 1.5%); hoarseness (CIC320 0.0%, CIC640 1.5%, FP880 3.6%, PBO 0.7%); and pharyngitis (CIC320 3.1%, CIC640 3.1%, FP880 5.1%, PBO 2.9%). Treatment of patients with moderate-to-severe asthma with CIC HFA-MDI 160 μg bid or 320 μg bid resulted in an incidence of oropharyngeal side effects similar to PBO and less than FP.