Ciclesonide | place in therapy review The PAQLQ is a 23-item questionnaire that is appropriate for children between the ages of 7 and 17 years and focuses on three domains (symptoms, emotional function, and activity limitation). A change in score of 0.5 reflects a minimally important difference. Both interviewer- and self-administration formats of the PAQLQ are available (Juniper 1997). The impact of ciclesonide on the HRQOL of patients with asthma has been assessed (Table 8) (Bernstein et al. 2005; Miller et al. 2005; Nayak et al. 2005). In one study that included patients with severe persistent asthma (FEV1 40–65%), clinically significant changes in AQLQ (≥0.5) were noted in all three groups receiving ciclesonide 160 or 320 mcg, or fluticasone 440 mcg twice daily (Bernstein et al. 2005). The change in AQLQ with fluticasone was greater than that noted with either dose of ciclesonide, although the statistical significance of this difference was not reported. These HRQOL studies were only conducted for a period of 12 weeks, therefore, it is not known if improvements in QOL are sustainable or whether the changes translate to significant long- term patient improvement. Tolerability A major component of the rationale for the development of ciclesonide is the minimization of local and systemic side effects often experienced with inhaled corticosteroids. Ciclesonide has been well tolerated in clinical trials with most adverse effects reported as mild. It is anticipated that the airway activation of ciclesonide will reduce the incidence of adverse effects compared with currently available inhaled corticosteroids. Although there are some data from longer term studies, the bulk of the evidence supporting the lack of systemic effects with ciclesonide therapy is limited to 12 weeks of treatment. Further long-term data will be necessary to confirm if ciclesonide offers an advantage over the other inhaled corticosteroids. Local adverse effects Local adverse effects associated with the use of inhaled corticosteroids include perioral dermatitis, tongue hypertrophy, cough during inhalation, and sensation of thirst. The most frequently reported clinically significant effects are oropharyngeal candidiasis and dysphonia (Roland et al. 2004). Deposition of active medication in the oropharyngeal cavity is dependent on the delivery device and can be decreased with the use of spacers. These adverse effects, while they are not considered to be clinically serious, are troublesome and may affect patient adherence (Goeman 2002). Oropharyngeal deposition of ciclesonide (metered-dose inhaler with hydrofluoroalkane propellant) is reduced compared with fluticasone (metered-dose inhaler with hydrofluoroalkane propellant) and budesonide (metered-dose inhaler with CFC) (Nave et al. 2005a; Richter et al. 2005). This reduction in oral deposition is expected to correlate with a lower rate of local adverse effects. In a pooled analysis of phase II and phase III studies, data from 12 251 patients who received ciclesonide (n=7706), active control [budesonide, beclomethasone, or fluticasone (n=3330)], or placebo (n=1215) 244 Table 9 | Incidence of oropharyngeal adverse events with ciclesonide compared with placebo or active treatmenta (adapted from Engelstätter et al. 2005) Adverse event Incidence of event/patient year Ciclesonide Placebo Active controlb Candidiasis Hoarseness 0.02 0.03 0.02 0.03 aCough not reported. bBeclomethasone, budesonide, or fluticasone. 0.07 0.07 for 12 weeks were analyzed to determine the incidence of oropharyngeal adverse events (candidiasis, hoarseness, cough) (Engelstätter et al. 2005). The incidence of local adverse events per patient year was similar in the ciclesonide and placebo group; oral candidiasis and hoarseness occurred less frequently in the ciclesonide group compared with the active control group (P value not reported) (Table 9). In a subanalysis, fewer patients in the ciclesonide group experienced an oral adverse event compared with patients in the fluticasone subgroup (P<0.0001). There is limited evidence that this lower frequency of oral adverse effects is maintained when treatment exceeds 12 weeks. A single open-label study that followed a 12-week placebo-controlled trial reported oropharyngeal side effects in 10 of 228 patients treated with ciclesonide (3.5%) (Chapman et al. 2002). After 24 weeks of treatment in an open-label study involving 528 patients, oral candidiasis or dysphonia were reported by 5.1% of patients receiving ciclesonide 320 mcg twice daily, significantly less than the 12.8% for fluticasone 330 mcg twice daily (P=0.0014) (Bateman et al. 2006c). Systemic adverse effects Systemic effects of inhaled corticosteroids occur because a large percentage (80%) of an administered dose of active drug is swallowed (Roland et al. 2004). Additional systemic exposure can occur as the drug is absorbed from the pulmonary fluid into the systemic circulation (Hübner et al. 2005). The amount of drug that is available to the systemic circulation, method of delivery, and lipophilicity of the drug influence risk of systemic side effects. The extent of systemic exposure with inhaled corticosteroids is typically reported by the magnitude of HPA axis suppression, serum and urinary cortisol concentrations, and effects on bone growth or mineralization. Systemically active corticosteroids bind to glucocorticoid receptors in the hypothalamus and adrenal pituitary causing a decrease in the amount of corticotropin- releasing hormone and adrenocorticotropic hormone leading to decreased cortisol secretion (Lipworth et al. 2005). HPA axis suppression and cortisol levels There is clear evidence that ciclesonide does not cause HPA axis suppression after 12 weeks of treatment. © 2006 Core Medical Publishing Limited