OBJECTIVE:To compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug (CIC40), 80 mug (CIC80), and 160 mug (CIC160) with placebo in children with persistent asthma of all severities. STUDY DESIGN:Overall, 1031 children age 4 to 11 years were randomized into 2 identical double-blinded, placebo-controlled, parallel group studies consisting of a run-in phase followed by 12 weeks of treatment. Both studies were designed to allow for a prespecified integrated analysis. The primary outcome variable was change in forced expiratory volume in 1 second (FEV(1)) percent predicted between baseline and study end; treatment comparisons were assessed using analysis of covariance. Additional endpoints included asthma symptom scores, daily albuterol use, and safety, including hypothalamic-pituitary-adrenal (HPA) axis function. RESULTS:Baseline characteristics were comparable; 59.4% of patients had moderate asthma, and 24.1% had severe asthma. All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1) percent predicted versus placebo (CIC40, 11.97; CIC80, 13.58, P <.05; CIC160, 14.17, P < .01). Significant improvements in asthma symptoms (P < .01) and reductions in albuterol use were reported. Ciclesonide was well tolerated with no effect on HPA axis function. CONCLUSIONS:In this integrated analysis, ciclesonide was effective and well tolerated in children with persistent asthma.

RATIONALE: To evaluate the effects of mometasone furoate dry powder inhaler (MF-DPI) 100 mcg administered once daily in the evening (QD PM) on health-related quality of life (HQOL) in children with asthma previously maintained on inhaled corticosteroids (ICS). METHODS: A randomized, placebo-controlled, 12-week study in children (4 - 11 years of age) with asthma evaluated (as secondary efficacy variables) the HQOL effects of MF-DPI 100 mcg QD PM, MF-DPI 100 mcg BID, and placebo. The HQOL data were collected using the Child Health Questionnaire - Parent Form (CHQ-PF28) and an asthma-specific module (ASM). The primary HQOL variables were changes from baseline in the physical summary score (PSS) of CHQ-PF28, and in the disability domain of the ASM. Data for the HQOL domains were analyzed for Week 8, Week 12 and endpoint using ANOVA. RESULTS: Of 296 randomized subjects, 292 (99%) completed both HQOL questionnaires at baseline and endpoint. Mean HQOL scores were similar among treatment groups at baseline, and suggested impaired function and well-being compared with the general population. At endpoint, the mean PSS improved significantly with MF-DPI 100 mcg QD PM vs placebo (3.4 and -2.1, respectively; p = 0.002). The mean ASM-disability score also improved significantly with MF-DPI 100 mcg QDPM vs placebo (9.2 and 0.3, respectively; p<0.001). Mean PSS and ASM-disability improvements with MF-DPI 100 mcg BID (2.3 and 6.8, respectively) were similar to those observed with MF-DPI 100 mcg QD PM. CONCLUSIONS: Treatment with MF-DPI 100 mcg QD PM significantly improves quality of life in children with asthma.

This multicenter study investigated whether beclomethasone dipropionate in hydrofluoroalkane-134a propellant (HFA-BDP) is effective in controlling asthma in children at a total dose as low as 100 μg/d. A group of 319 children with mild to moderate asthma, ranging in age from 6 to 12 years, were randomly assigned to receive double-blind treatment with HFA-BDP, 50 μg twice daily; HFA-BDP, 100 μg twice daily; or HFA-placebo for 12 weeks. The Maxair™ Autohaler™ (3M Pharmaceuticals) inhalation device was used to facilitate medication delivery. Median compliance with study medication was 62.5% in the intent-to-treat population, and was lower in the HFA-BDP 200 μg/d group (55.8%) compared to the HFA-BDP 100 μg/d (67.0%) and placebo (66.0%) groups. Median compliance was 80.0% in the evaluable-for-efficacy population. Mean change from baseline at week 12 in forced expiratory volume in 1 second (FEV1) percent predicted was significantly greater than placebo in the HFA-BDP 100 μg/d group (p ≤ 0.01) but not the 200 μg/d group in both the intent-to-treat and evaluable-for-efficacy analyses. In the evaluable-for-efficacy analysis, there was a significant trend for increasing median change from baseline in FEV1 as percent predicted with increasing doses of HFA-BDP (p < 0.0001). A cumulative distribution plot demonstrated a greater response to HFA-BDP 200 μg/d among those patients in the evaluable-for-efficacy analysis, which was the subset of patients who were compliant with treatment, compared to those in the intent-to-treat analysis, who were less compliant. In conclusion, HFA-BDP, 100 μg/d, demonstrated superior efficacy to placebo in improving asthma control in children with mild to moderate asthma. Compliance was particularly low in the 200 μg/d group, suggesting insufficient data to determine efficacy for this dose. However, further analysis supported the efficacy of this dose in patients who used their medication as instructed.

OBJECTIVE:Intranasal corticosteroids are used widely for the treatment of allergic rhinitis because they are effective and well tolerated. However, their potential to suppress growth of pediatric subjects with allergic rhinitis continues to be a concern, particularly in light of reports of growth suppression after treatment with intranasal beclomethasone dipropionate or intranasal budesonide (see the article by Skoner et al in this month's issue). A 1-year study of prepubertal patients between 3 and 9 years of age with perennial allergic rhinitis was conducted to assess the effects on growth of mometasone furoate aqueous nasal spray (MFNS), a new once-daily (QD) intranasal corticosteroid with negligible bioavailability.METHODS:This was a randomized, placebo-controlled, double-blind, multicenter study. Ninety-eight subjects were randomized to treatment with either MFNS 100 microg QD or placebo for 1 year. Each subject's height was required to be between the 5th and 95th percentile at baseline, and skeletal age at screening was required to be within 2 years of chronological age, as determined by left wrist x-rays. Washout periods for medications that affect either childhood growth or allergic rhinitis symptoms were established based on estimated period of effect, and these medications were prohibited during the study. However, short courses of either oral prednisone lasting no longer than 7 days or low-potency topical dermatologic corticosteroids lasting no longer than 10 days were permitted if necessary. Height was measured with a calibrated stadiometer at baseline and at 4, 8, 12, 26, 39, and 52 weeks, and the primary safety variable was the change in standing height. The rate of growth was also calculated for each subject as the slope (linear regression) of the change in height from baseline using data from all visits of subjects who had at least 2 visits. Hypothalamic-pituitary-adrenocortical- (HPA)-axis function was assessed via cosyntropin stimulation testing at baseline and at 26 and 52 weeks. All analyses were based on all randomized subjects (intent-to-treat principle). The change from baseline in standing height was analyzed by a 2-way analysis of variance that extracted sources of variation attributable to treatment, center, and treatment-by-center interaction.RESULTS:Demographic characteristics were similar at baseline. Eighty-two subjects completed the study (42 in the MFNS group and 40 in the placebo group), and 93% of subjects achieved at least 80% compliance with therapy. After 1 year of treatment, no suppression of growth was seen in subjects treated with MFNS, and mean standing heights were similar for both treatment groups at all time points. For the primary safety variable (change in height from baseline), both treatment groups were similar at all time points except for weeks 8 and 52. Subjects treated with MFNS had a slightly greater mean increase in height than subjects treated with placebo at these time points: the change in height was 6.95 cm versus 6.35 cm at the 1-year time point. However, the rate of growth (.018 cm/day) averaged for all time points over the course of the study was similar for both treatment groups. Additional analyses found that MFNS did not retard growth in any sex or age subgroup of subjects. The use of exogenous corticosteroids other than the study drug was also similar among the 2 treatment groups. Results from cosyntropin stimulation testing confirmed the absence of systemic effects of MFNS. The change from baseline in the difference between prestimulation and poststimulation levels was similar for both treatment groups after 1 year of treatment, with no evidence of HPA-axis suppression in MFNS-treated subjects at any time point. Incidences of treatment-related adverse events were similar for both treatment groups, with 16% of MFNS-treated subjects reporting adverse events, compared with 22% of placebo-treated subjects.CONCLUSIONS:(ABSTRACT TRUNCATED)