CIC 160 qd CIC 640 qd Placebo CIC 80 qd CIC 320 qd Placebo CIC 80 qd CIC 160 qd CIC 320 qd Placebo CIC 320 bidd CIC 640 bidd Placebod 107 112 110 120 115 125 257 250 255 249 47 49 45 60–90 60–95 60–85 40–80 FEV1 (mL) Maintained with both dosesa –144 +130 (P=0.0044)b +190 (P=0.0001)b –30 +280 (P≤0.0007)b +290 (P≤0.0007)b +310 (P≤0.0007)b +170 Trend toward higher NR valuese NR NR NR NR NR NR Ciclesonide | place in therapy review +190 (P=0.0203)b +200 (P=0.0197)b +40 +59 +9 –161 NR NR NR NR Stable for both doses Chapman et al. (P<0.0001) 2005 –29 +2c (P=0.0012)b +3c (P=0.0006)b –18 10.93c (P=0.0003)b 21.06c (P<0.0001)b 17.22c (P<0.0001)b –1.70c +4.32b,c +15.97b,c –0.7b,c Langdon et al. 2005 Pearlman et al. 2005 Bateman et al. 2006b Table 5 | Effect of ciclesonide on lung function in patients with moderate to severe asthma (level 2 evidence; all trials randomized, double-blind, parallel-group, placebo-controlled, 12 weeks’ duration) Treatment (mcg) n Baseline FEV1 (% of predicted) Outcome Reference FEV1 (%) change from baseline FVC (mL) Morning PEF (L/min) All P values vs placebo. aP=0.007 for CIC 160 and P=0.0108 for CIC 640. bReported as a mean value. cPEF change from baseline to week 12. dPatients also received oral prednisone 5–30 mg/day and/or 10–60 mg on alternate days. eP=0.0237 CIC 320 bid vs placebo, P=0.0277 CIC 640 bid vs placebo. +, increase over study period; –, decrease over study period; bid, twice daily; CIC, ciclesonide; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; NR, not reported; NS, not significant; PEF, peak expiratory flow; qd, once daily. 2002). More recent data, however, show that compared with ciclesonide 160 mcg once daily, ciclesonide 320 mcg twice daily resulted in significantly improved PEF (P=0.0014) in 680 patients with severe asthma (Bateman et al. 2006a). A dose–response effect was also demonstrated in a 3-week study investigating ciclesonide 40, 80, 160, and 320 mcg on exercise-induced bronchoconstriction in 26 patients with mild asthma (Subbarao et al. 2006). Daily dosing given either in the morning or in the evening is associated with positive treatment response (Postma et al. 2001). Ciclesonide 80 mcg has also been shown to block allergen- induced lung function responses and measures of airway inflammation in patients with mild atopic asthma (Gauvreau et al. 2005). In this randomized three-way crossover study 21 patients were treated with ciclesonide 40 or 80 mcg or placebo for 7 days and challenged with inhaled allergen. Compared with placebo, ciclesonide 80 mcg/day attenuated the allergen-induced airway response (P<0.025), the sustained fall in FEV1 measures 24 hours postchallenge (P<0.025), and the allergen-induced accumulation of eosinophils into the airways (P<0.025). Similarly, after 4 weeks of treatment with ciclesonide 160 mcg once daily, inflammatory response as assessed by AMP bronchial challenge, exhaled nitric Core Evidence 2006;1(4) oxide, and sputum eosinophil count was significantly reduced in 17 patients with asthma (Wilson et al. 2006). In larger studies comparing ciclesonide treatment with an active control, significant improvements in airflow (changes in FEV1 and FVC) were reported with ciclesonide and active control in all studies—with the exception of Boulet et al. (2006a) (Table 6). Neither treatment with budesonide nor ciclesonide resulted in improved FEV1 or FVC; however, the decrease in FVC was significantly less with ciclesonide than with budesonide (P=0.01). The decline in FEV1 seen with both drugs was expected, since all patients routinely required “moderate” doses of inhaled corticosteroids to control their asthma, were poorly controlled, and had received budesonide 1280 mcg/day during a 2- to 4-week run-in phase, which was stopped prior to randomization to the study regimens. A subsequent abstract by the same authors reported that treatment with ciclesonide 320 mcg once daily and fluticasone propionate 200 mcg twice daily improved FEV1 to a comparable degree (171 mL and 186 mL, respectively; P<0.0001 vs baseline) (Boulet et al. 2006b). PEF values were also significantly improved from baseline with ciclesonide and active treatment (Table 6). In one study comparing 239