Ciclesonide | place in therapy review CIC 160 bid CIC 320 bid FP 440 bida Placebo CIC 80 qd CIC 160 qd CIC 320 qd Placebo CIC 40 qd CIC 80 qd CIC 160 qd Placebo CIC 160 qd BUD 400 qd Study in pediatric patients aged 7–17 years n 531 40–65 1015 60–85 793 60–85 340 173 NR Table 8 | Effect on quality of life of ciclesonide compared with placebo or active treatment (level 2 evidence; all studies randomized, multicenter, double-blind, parallel-group, placebo-controlled, 12 weeks’ duration) Treatment (mcg) Baseline FEV1 (% of predicted) Outcome: patients achieving an MID (≥0.5) in QOL score (%) Reference Studies in adults and adolescents aged >12 years 42.5 43 58.8 26.8 47 50 50.6 31 46.1 50 52.5 36.5 53.8 50.6 Bernstein et al. 2005 Nayak et al. 2005 Miller et al. 2005; Gelfand et al. 2006 Vermeulen et al. 2006 aFP dose 37% higher to maintain blinding. bid, twice daily; BUD, budesonide; CIC, ciclesonide; FEV1, forced expiratory volume in 1 s; FP, fluticasone propionate; MID, minimally important difference; qd, once daily. placebo. These improvements were associated with significantly more symptom-free days among children receiving ciclesonide 80 (52.44%; P<0.0001) and 160 mcg/day (48.77%; P=0.0139) compared with placebo (42.52%), and significantly lower use of rescue medication (P<0.01). Ciclesonide improved symptom scores and reduced nighttime awakening at all three doses. There is evidence that ciclesonide 160 mcg/day, given either as a single dose or as 80 mcg twice daily, is as effective as fluticasone 88 mcg twice daily and budesonide 400 mcg once daily. In 556 children, ciclesonide and fluticasone increased mean FEV1 by 298 and 297 mL, respectively, after 12 weeks (Pedersen et al. 2004a). Corresponding increases in mean morning and evening PEF were 31 and 29 L/min with ciclesonide, and 34 and 29 L/min with fluticasone. Mean FEV1 increased by 220 mL in 340 children aged 6–11 years following 12 weeks’ treatment with ciclesonide and by 253 mL in 173 receiving budesonide (von Berg et al. 2006). Asthma symptoms were absent in an almost identical proportion of days in each group (74% for ciclesonide and 73% for budesonide), and both drugs were comparable in improving symptom scores and reducing rescue medication use. Quality of life HRQOL measures offer an important patient perspective into the therapeutic management of asthma. Because asthma is a chronic disease that may affect a patient’s ability to participate in normal daily activities including work, school, and extracurricular activities, it is important to include the impact of a medication on Core Evidence 2006;1(4) quality of life in a determination of its effectiveness and place in therapy. There is often a disconnection between medication- induced changes in airways as assessed by the clinician and patient perceptions of their functional status. The effect of treatment on HRQOL is now recognized as an important gauge of therapy and should be used as a determinant of treatment effect. HRQOL measurement provides the clinician with important insight into the burden of disease and provides an appreciation of the effect of treatment on functional status. Treatments with positive HRQOL effects may improve patient compliance with therapy and improve overall patient satisfaction (Gerth van Wijk 2005). Although several HRQOL tools have been used to evaluate HRQOL in patients with asthma, in the ciclesonide studies that provided HRQOL information, the Asthma Quality of Life Questionnaire (AQLQ) and the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) were the tools used for assessment. The reliability and validity of the AQLQ has been verified in several studies (Gupchup et al. 1997; van der Molen et al. 1997; Sanjuas et al. 2002). The AQLQ is a 32-item, four-domain (symptoms, emotional function, activity limitation, and breathlessness) questionnaire that can be interviewer- or self-administered. Using this questionnaire, a change in score of 0.5 is considered the minimum change necessary for clinical significance. A separate pediatric-based questionnaire is necessary for children because it is clear that conventional measures of the effectiveness of therapy (asthma severity, spirometry, and medication use) and parents’ perceptions of a child’s functionality weakly correlate with how children actually feel and their ability to participate in activities of daily life (Juniper et al. 1996). 243