The effects of intranasal triamcinolone acetonide and intranasal fluticasone propionate on short-term bone growth and HPA axis in children with allergic rhinitis.

OBJECTIVE: The purpose of this study was to evaluate the effects of triamcinolone acetonide (TAA) and fluticasone propionate (FP) aqueous nasal sprays on short-term lower-leg growth velocity and hypothalamic-pituitary-adrenal (HPA-axis function in pediatric subjects. METHODS: In this controlled, double-blinded (TAA) or single-blinded (FP), four-way crossover trial, 59 subjects (mean age: 7.2 years) were randomized to receive each of four 2-week treatments in random order: TAA nasal spray 110 microg, TAA nasal spray 220 microg, FP nasal spray 200 microg, and placebo, administered by a third party once daily with a 2-week washout period between treatments. Lower-leg growth velocity was measured by knemometry, and HPA-axis function was measured using 12-hour overnight urinary cortisol levels. RESULTS: Forty-nine subjects completed all four treatments and were included in the analyses. Mean growth velocity (+/- standard error) was 0.46 (+/- 0.06) mm/week for placebo, 0.37 (+/- 0.06) and 0.31 (+/- 0.06) mm/week for TAA nasal spray 110 and 220 microg, respectively, and 0.37 (+/- 0.06) mm/week for FP nasal spray. The treatment effect on mean growth velocity compared with placebo was -19.6% with TAA 110 microg, -32.6% with TAA 220 microg, and -21.7% with FP; none of these effects was considered statistically or clinically significant according to predefined criteria. No significant differences in changes in urine cortisol/creatinine ratios were observed between TAA 110 microg or 220 microg and placebo (4.38, 3.60, and -0.67, respectively, P > or = 0.157). In contrast, the change in mean urine cortisol/creatinine ratio values for FP (-3.59) were significantly lower compared with TAA 220 microg (P = 0.033) and placebo (P = 0.003). Knemometry exhibited less time-dependent variability than overnight urinary cortisol measurements. CONCLUSIONS: Neither TAA nor FP had a clinically significant effect on lower-leg growth velocity. In contrast to FP, TAA nasal spray did not significantly affect HPA-axis function when used over a 2-week interval.     

Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma

BACKGROUND: Inhaled corticosteroids (ICS) are recommended therapy for persistent asthma, although side effects can limit appropriate use. Ciclesonide, a novel ICS, is activated in the lung, thereby reducing systemic activity and side effects. This 12-week, double-blind, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma. METHODS: After a 2-week baseline period in which current ICS treatment was continued, 329 patients were randomized to receive ciclesonide 160 microg (n = 107) or 640 microg (n = 112) (ex-actuator doses, equivalent to 200 and 800 microg ex-valve, respectively), or placebo (n = 110) once daily in the morning. Efficacy was monitored by asthma symptom scores, rescue medication use, morning and evening peak expiratory flow (PEF) measurements, spirometry, and probability of study completion without experiencing lack of efficacy. RESULTS: Morning PEF remained stable with either ciclesonide dose but decreased with placebo; the differences were significant (P < 0.0001) for both ciclesonide doses vs placebo. The forced expiratory volume in 1 s and forced vital capacity decreased significantly with placebo (P < 0.005), but were unchanged with ciclesonide. Lack of efficacy was significantly greater for patients switched to placebo (63%) than it was for those treated with ciclesonide 160 microg (30%) (P < 0.0001 vs placebo) or ciclesonide 640 microg (31%) (P < 0.0001 vs placebo). There were no significant differences between the two tested doses of ciclesonide with respect to efficacy and safety. Serum and 24-h urine cortisol were unaffected by ciclesonide treatment. Both doses of ciclesonide were well tolerated with no cases of oral candidiasis. CONCLUSION: Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma.     

Short-term lower leg growth rate in children with rhinitis treated with intranasal mometasone furoate and budesonide.

BACKGROUND: Mometasone furoate (MF) aqueous nasal spray is a potent intranasal glucocorticoid with low systemic bioavailability. Knemometry has been shown to be a sensitive method of detecting systemic effects of exogenous steroids in children. OBJECTIVE: We sought to assess whether MF (100 or 200 microg) or budesonide intranasal aqueous spray (400 microg) influences the short-term lower leg growth rate in children with seasonal or perennial allergic rhinitis. METHODS: MF, budesonide, and placebo were administered once daily for 2 weeks to 22 children aged 7 to 12 years (mean, 10 years) in a randomized, double-blind, crossover study. Lower leg measurements were done before and after each 2-week treatment period. Two-week washout intervals separated each treatment period. RESULTS: There were no significant differences in lower leg growth rates among the MF 200 microg (0.95 +/- 0.79 mm; mean +/- SD), budesonide 400 microg (0.73 +/- 0.61 mm), or placebo (0.69 +/- 0.70 mm) groups. The growth rate of the group receiving a 100-microg dose of MF (1.16 +/- 0.67 mm) was greater than that for the group receiving placebo (P =.024) or budesonide (P =.033). No statistically significant sequence effect (P =.11), carry-over effect (P =.24), overall treatment effect (P =.086), or period effect (P =.065) was detected. CONCLUSION: No short-term adverse effects on linear lower leg growth rates were detected after once daily MF or budesonide at clinically relevant doses.     

Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma.

BACKGROUND: Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events. OBJECTIVE: To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma. METHODS: This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator. RESULTS: For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate. CONCLUSIONS: These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.     

The systemic safety of inhaled corticosteroid therapy: a focus on ciclesonide.

OBJECTIVE: To review the potential systemic activity of ciclesonide and its active metabolite, desisobutyryl-ciclesonide, by evaluation of the effects on hypothalamic-pituitary-adrenal (HPA) axis function. DATA SOURCES: EMBASE and MEDLINE searches using the keyword ciclesonide, without date restrictions, were conducted to identify published articles that related to clinical trials that included ciclesonide. STUDY SELECTION: The primary articles that reported systemic safety data for ciclesonide were reviewed. RESULTS: Ciclesonide (320-1,280 microg/d) demonstrated no detectable, clinically relevant effect on HPA axis function as evaluated by basal cortisol excretion measurements and dynamic stimulation tests. Furthermore, ciclesonide had no effect on the normal diurnal rhythm of endogenous cortisol secretion while simultaneously improving pulmonary function and reducing bronchial hyperresponsiveness. These results suggest that ciclesonide has a low systemic activity that may be attributable to unique pharmacologic properties, including a high degree of serum protein binding, a low oral bioavailability, and rapid systemic elimination, that reduce the level of systemically available pharmacologically active drug. CONCLUSIONS: Even at the higher doses used to treat more severe cases of asthma, ciclesonide was observed to have no effect on HPA axis function. These data, in conjunction with the observed clinical efficacy, suggest that ciclesonide may have an improved therapeutic margin compared with some other currently available inhaled corticosteroid treatments and, therefore, the potential to improve therapeutic outcomes.     

Mometasone furoate antagonizes AMP-induced bronchoconstriction in patients with mild asthma

BACKGROUND: Mometasone furoate (MF) is a new potent corticosteroid for use in treating asthma. OBJECTIVE: To test the lower range of the dose-response curve, effects of MF delivered by dry powder inhaler (DPI) on AMP-induced bronchoconstriction were compared with those of placebo. METHODS: In a placebo-controlled, 3-phase cross-over, single-center, double-blind study, 15 patients with mild asthma were randomized to three 2-week treatment phases (separated by 4-week washout phases) with MF DPI 50 microg twice daily, MF DPI 100 microg twice daily, or placebo. AMP challenge was performed before and at the end of each treatment phase. RESULTS: Thirteen patients completed all 3 phases and were included in the primary efficacy analysis. Treatment with MF DPI 50 microg twice daily or with MF DPI 100 microg twice daily significantly reduced the bronchoconstrictor response to AMP, displacing the dose-response curve to the right by 2.81 and 3.11 doubling dilutions, respectively, compared with placebo (P <.001). The improvement in FEV(1) over the 2-week treatment phase was significantly (P < or =.033) greater during treatment with MF DPI 50 microg or 100 microg twice daily than with placebo. Peak expiratory flow rate, wheezing scores, difficulty breathing scores, nocturnal awakenings requiring salbutamol, and puffs of salbutamol per day also indicated a greater improvement in respiratory function and symptoms of asthma with MF DPI 50 or 100 microg twice daily than with placebo. Both doses of MF DPI were well tolerated. CONCLUSIONS: Treatment with low doses of MF DPI decreased airway responsiveness to AMP challenge and improved secondary measures of pulmonary function and asthma symptoms.     

Effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic rhinitis.

BACKGROUND: Ciclesonide is an investigational corticosteroid under development for treatment of allergic rhinitis. Ciclesonide is converted to active metabolite, desisobutyryl-ciclesonide (des-CIC), by upper and lower airway esterases. In vitro studies in human nasal epithelial cells and bronchial epithelial cells have demonstrated a long duration of anti-inflammatory activity of des-CIC. OBJECTIVE: To evaluate the dose-dependent efficacy and safety of a hypotonic intranasal formulation of ciclesonide in patients with seasonal allergic rhinitis (SAR). METHODS: This was a phase 2, randomized, parallel-group, double-blind, placebo-controlled study. Adults (n = approximately 145 per treatment group) with a minimum 2-year history of SAR received placebo or ciclesonide (25, 50, 100, or 200 microg/d) for 14 days. The primary end point was change in the sum of morning and evening reflective total nasal symptom scores (TNSSs) over 2 weeks. Safety was monitored throughout the study. RESULTS: Ciclesonide, 100 microg/d (P = .04) and 200 microg/d (P = .003), significantly improved the sum of morning and evening reflective TNSS vs placebo at more than 2 weeks of treatment. Baseline values for morning and evening reflective TNSS ranged from 17.80 to 18.82 across treatment groups. The average change from baseline in reflective TNSS was -4.2 for placebo and -4.8, -4.8, -5.3, and -5.8 for ciclesonide, 25, 50, 100, and 200 microg/d, respectively. There were no dose-related differences in the incidence of adverse events among treatment groups. CONCLUSIONS: Results from this study indicate that 100-microg and 200-microg daily doses of ciclesonide are effective in the treatment of SAR. Ciclesonide, 200 microg/d, appears to be the optimal dose studied for reducing the symptoms of SAR while maintaining an acceptable safety profile.     

Short-term lower leg growth in asthmatic children treated with inhaled beta2-agonists

BACKGROUND: Knemometry studies of growth suppressive effects of inhaled glucocorticoids in children with asthma usually allow participating children to use concomitant inhaled beta2-agonists. Systemic beta2-agonists, however, have been found to suppress growth hormone secretion and this has caused concern about a possible confounding effect of inhaled beta2-agonists on results of growth studies of exogenous glucocorticoids. AIM: The study evaluated whether inhaled salbutamol adversely affects short-term growth. SUBJECTS AND METHODS: Fifteen children aged 6-12 years with mild asthma were enrolled in a single-blind, randomized crossover study with two 2-week treatment periods and a 1-week run-in. During the active period treatment dry powder salbutamol (Ventoline Diskhaler) 200 microg was inhaled three times a day. During the comparative period no treatment was given. Knemometry of the right lower leg was performed on the first and the last day of each period. RESULTS: Mean lower leg growth rates (SEM) during no-treatment and salbutamol periods were 0.35 (0.06) and 0.42 (0.07) mm per week, respectively (P = 0.35, t = -0.98, 95% CI: 0.25-0.93 mm per week). CONCLUSIONS: Inhaled salbutamol 200 microg three times daily does not suppress short-term growth in asthmatic children. Inhaled beta2-agonists in equipotent doses and regimens can be safely used in short-term knemometric growth studies of exogenous glucocorticoids without any risk of confounding the results.     

Effects of fluticasone propionate, triamcinolone acetonide, prednisone, and placebo on the hypothalamic-pituitary-adrenal axis

BACKGROUND: Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis. OBJECTIVE: The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress. METHODS: This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 microg or 220 microg twice daily, triamcinolone acetonide aerosol 200 microg 4 times daily or 400 microg twice daily, prednisone 10 mg once daily, and placebo. RESULTS: After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P <.05) reduced after treatment with prednisone compared with the other treatment groups. Mean 8-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P 相似文献   

Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma

BACKGROUND: Inhaled corticosteroids are recommended as first-line therapy for persistent asthma. OBJECTIVE: We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma. METHODS: An integrated analysis of 2 identical, multicenter, double-blind, randomized, parallel-group, placebo-controlled trials was conducted. Patients (n = 1015; aged > or =12 years) with mild-to-moderate asthma (FEV1 of 60% to 85% of predicted value) were randomized to ciclesonide 80 microg (CIC80), 160 microg (CIC160), or 320 microg (CIC320), once daily (exactuator doses) in the morning or placebo for 12 weeks. RESULTS: All ciclesonide groups showed significant improvements from baseline to week 12 in FEV1 compared with the placebo group (CIC80, 0.12 L [P = .0007]; CIC160, 0.13 L [P = .0004]; and CIC320, 0.14 L [P < .0001]). Likewise, FEV1 percent predicted, morning and evening peak expiratory flow, 24-hour asthma symptom score, daily albuterol use, and nighttime awakenings were significantly improved in all ciclesonide groups compared with the placebo group. Overall ciclesonide safety profile and rates of oropharyngeal adverse events for all groups were low and similar to those of the placebo group. Fewer ciclesonide-treated patients exhibited asthma-aggravated adverse events, and fewer ciclesonide-treated patients discontinued the study for any reason or because of a lack of efficacy compared with those in the placebo group. No suppression of hypothalamic-pituitary-adrenal-axis function (as assessed by means of 24-hour urinary cortisol levels corrected for creatinine and peak serum cortisol levels after stimulation with low-dose [1 microg] cosyntropin) was observed with any dose of ciclesonide. CONCLUSIONS: In this integrated analysis, ciclesonide once daily administered in the morning is effective and well tolerated.     

Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma

BACKGROUND: Inhaled corticosteroid therapy improves exercise symptoms in asthmatic subjects. OBJECTIVE: We sought to evaluate exercise-induced bronchoconstriction (EIB) as a method of determining the dose and time responses of inhaled corticosteroid therapy. METHODS: In this double-blind, randomized, cross-over study with 2 parallel arms, 4 doses of inhaled ciclesonide (40 microg and 160 microg or 80 microg and 320 microg) were compared over 3 weeks of treatment. Twenty-six asthmatic subjects (age range, 14-27 years) with baseline FEV1 values of greater than 70% of predicted value were enrolled. The primary outcome was the maximum percentage decrease in FEV1 after standardized exercise challenge. RESULTS: After 1 week of therapy, the mean +/- SEM reduction in maximum decrease in FEV1 in the ciclesonide 40-microg/80-microg dose group was 9% +/- 2.6% (95% CI, 3.9% to 14%), with no additional reduction thereafter. In the ciclesonide 160-microg/320-microg dose group, there was an 8.7% +/- 2.5% (95% CI, 3.7% to 13.7%) reduction in maximum decrease in FEV1 after week 1, which continued in a linear fashion during subsequent weeks of treatment. No difference was found between the 2 treatment arms in the temporal response of EIB to ciclesonide treatment. The maximum percentage attenuation in EIB achieved was 51.1% +/- 7.9%, which was achieved by using the 320-microg dose after 3 weeks of treatment. CONCLUSIONS: A significant improvement in EIB was demonstrated for all doses of ciclesonide. Use of 160 microg/320 microg of ciclesonide resulted in a continuing improvement in FEV1 with time, and no plateau was seen in protective effect during 3 weeks of treatment. CLINICAL IMPLICATIONS: Attenuation in exercise-induced decrease can be seen as early as after 1 week of therapy with inhaled ciclesonide at doses greater than 40 microg. However, maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 microg, even after 3 weeks of therapy.     

Effect of budesonide aqueous nasal spray on hypothalamic-pituitary-adrenal axis function in children with allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are safe and effective for treating allergic rhinitis in adults. Since children may receive more systemic corticosteroid on a dose-per-weight basis than adults, the safety of corticosteroid therapy in pediatric patients is an important issue. OBJECTIVE: To determine the effects of treatment with budesonide aqueous nasal spray using the recommended once-daily dose for adults and children 6 years and older on hypothalamic-pituitary-adrenal (HPA) axis function in pediatric patients with allergic rhinitis. METHODS: In a 6-week, multicenter, double-blind, placebo-controlled study, 78 patients aged 2 to 5 years with allergic rhinitis were treated with budesonide aqueous nasal spray (64 microg/d) or placebo. Mean change in morning plasma cortisol levels from baseline to study end 0, 30, and 60 minutes after low-dose (10-microg) cosyntropin stimulation and mean change in the difference from 0 to 30 minutes and from 0 to 60 minutes after cosyntropin stimulation were used to evaluate HPA axis function. RESULTS: Mean change from baseline to study end in plasma cortisol levels 0, 30, and 60 minutes after cosyntropin stimulation and the difference from 0 to 30 minutes and from 0 to 60 minutes were not significantly different between the treatment and placebo groups (P > .05 for all). At the end of the study, 3 budesonide aqueous nasal spray and 6 placebo patients were classified as having subnormal HPA axis function. The safety and tolerability profile of budesonide aqueous nasal spray was comparable to that of placebo. CONCLUSIONS: Administration of budesonide aqueous nasal spray for 6 weeks was well tolerated and safe and had no measurable suppressive effects on HPA axis function in patients aged 2 to 5 years with allergic rhinitis.     

Efficacy and safety of ciclesonide, 200 microg once daily, for the treatment of perennial allergic rhinitis.

BACKGROUND: Ciclesonide is an intranasal corticosteroid approved for the treatment of allergic rhinitis (AR). OBJECTIVE: To evaluate the efficacy, safety, and quality-of-life benefits of intranasal ciclesonide, 200 microg once daily, for the treatment of perennial AR (PAR). METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, adults and adolescents with at least a 2-year history of PAR received intranasal ciclesonide, 200 microg, or placebo once daily for 6 weeks. Patient-evaluated total nasal symptom scores (TNSSs), physician-assessed overall nasal signs and symptoms severity scores, and Rhinoconjunctivitis Quality of Life Questionnaire scores were evaluated. RESULTS: Patient baseline characteristics were similar in the ciclesonide (n = 238) and placebo (n = 233) groups and were consistent with moderate PAR severity. Ciclesonide therapy significantly reduced average morning and evening reflective TNSSs compared with placebo (P < .001) and significantly reduced average morning and evening instantaneous TNSSs (P = .001) over 6 weeks of treatment. At the end point, a greater decrease from baseline was observed in physician-assessed overall nasal signs and symptoms severity for the ciclesonide group compared with the placebo group (P = .051). An appreciable improvement in combined Rhinoconjunctivitis Quality of Life Questionnaire scores at the end point was also observed in the ciclesonide group (P = .01 vs placebo). The frequency of adverse events was similar between treatment groups. CONCLUSIONS: In this study, intranasal ciclesonide treatment was associated with significant reductions in nasal symptoms and appreciable improvements in health-related quality of life in adult and adolescent patients with PAR. Ciclesonide was well tolerated, with a safety profile comparable with that of placebo.     

Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis.

BACKGROUND: Mometasone furoate nasal spray (MFNS) 400 microg, twice daily, as adjunctive treatment with oral antibiotic significantly improved symptoms of recurrent rhinosinusitis. OBJECTIVE: To evaluate the effectiveness and safety of MFNS 200 microg, twice daily, and 400 microg, twice daily, compared with placebo as adjunctive treatment with oral antibiotic for acute rhinosinusitis. METHODS: In this multicenter, double-blind, placebo-controlled study, 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin/clavulanate potassium (Augmentin, GlaxoSmithKline, Research Triangle Park, NC) 875 mg, twice daily, for 21 days with adjunctive twice daily MFNS 200 microg, MFNS 400 microg, or placebo nasal spray. Patients recorded scores of six rhinosinusitis symptoms and any adverse events twice daily. Pre- and postcosyntropin-stimulation plasma cortisol levels were measured in a subset of patients at selected study sites. RESULTS: Treatment with MFNS 200 microg or 400 microg, twice daily, produced significantly greater improvements in total symptoms score (primary efficacy variable) day 1 to day 15 average (50% and 51%, respectively) than placebo (44%, P < or = 0.017). Both doses of MFNS produced significant total symptoms score improvement over placebo by day 4, and maintained efficacy over the entire 21-day study. Relief of individual symptoms showed a similar pattern. Both doses of MFNS were well tolerated, and adverse events were similar to that of placebo. Cosyntropin stimulation showed no evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 microg or 400 microg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone.     

A dose-ranging study of mometasone furoate aqueous nasal spray in children with seasonal allergic rhinitis.

BACKGROUND: The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 microg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized. OBJECTIVE: This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population. METHODS: This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 microgram once daily, MFNS 100 microgram once daily, MFNS 200 microgram once daily, beclomethasone dipropionate 84 microgram twice daily (168 microgram/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29. RESULTS: The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group (P 相似文献   

Effects of ciclesonide and fluticasone propionate on allergen-induced airway inflammation and remodeling features

BACKGROUND: Several topical corticosteroids are available as anti-inflammatory treatment for asthma. Their comparative effects on allergic inflammation and airway remodeling are unclear. OBJECTIVE: We compared the effects of ciclesonide with those of fluticasone propionate in a Brown Norway rat model of chronic allergic asthma. METHODS: Rats sensitized and exposed to ovalbumin (OVA) were treated with dry powder vehicle, ciclesonide, or fluticasone (0.01, 0.03, and 0.1 mg/kg administered intratracheally) 24 hours and 1 hour before each of 6 OVA exposures. In a second protocol we administered 0.1 mg/kg ciclesonide or fluticasone only after the third OVA exposure. RESULTS: Ciclesonide at all doses inhibited the allergen-induced increase in airway eosinophils and T cells, reduced goblet cell hyperplasia, and decreased 5-bromo-2'-deoxyuridine-immunoreactive airway smooth muscle (ASM) and epithelial cells. At 0.03 and 0.1 mg/kg ciclesonide, bronchial hyperresponsiveness (BHR) was also inhibited. Fluticasone did not attenuate allergen-induced BHR, despite inhibiting airway eosinophils and T cells, goblet cell hyperplasia, and 5-bromo-2'-deoxyuridine-immunoreactive ASM and epithelial cells. Fluticasone (0.1 mg/kg) caused a significant reduction in body weight (9%) compared with ciclesonide (0.1 mg/kg). Ciclesonide did not change plasma corticosterone levels, whereas fluticasone (0.1 mg/kg) reduced them. In the second protocol both fluticasone and ciclesonide inhibited BHR, bronchial inflammation, goblet cell hyperplasia, and ASM proliferation. CONCLUSION: Ciclesonide potently inhibited chronic allergic inflammation, remodeling, and BHR without having an effect on body weight and the hypothalamic-pituitary-adrenal axis. Fluticasone prevented airway inflammation but not BHR, but both fluticasone and ciclesonide are effective at reversal of BHR, inflammation, and remodeling features.     

Long-term safety and efficacy of intranasal ciclesonide in adult and adolescent patients with perennial allergic rhinitis.

BACKGROUND: Ciclesonide is a corticosteroid in development for allergic rhinitis that has been shown to be safe and effective in seasonal allergic rhinitis and perennial allergic rhinitis (PAR) trials of up to 6 weeks in duration. However, the long-term safety and efficacy of ciclesonide are unknown. OBJECTIVE: To demonstrate the long-term safety of intranasal ciclesonide, 200 microg once daily, in patients with PAR. METHODS: Patients (> or = 12 years old) with a 2-year or longer history of PAR were randomized in a double-blind fashion to receive ciclesonide, 200 microg, or placebo once daily in the morning for up to 52 weeks. Spontaneous and elicited adverse events were monitored throughout the study. Ear, nose, and throat examinations were performed to evaluate local tolerability. Additionally, 24-hour urinary free cortisol level, morning plasma cortisol level, intraocular pressure, and lens opacification were monitored to evaluate the systemic safety of intranasal ciclesonide. Ciclesonide efficacy was determined by measuring 24-hour reflective total nasal symptom scores. RESULTS: No clinically relevant differences were observed between the ciclesonide and placebo groups in adverse events, ear, nose, and throat examinations, or 24-hour urinary free or morning plasma cortisol levels. Similarly, no clinically relevant differences were found between treatment groups in intraocular pressure, visual acuity, or lens opacification. With regard to efficacy, ciclesonide achieved a significantly greater reduction in 24-hour reflective total nasal symptom score compared with placebo over more than 52 weeks (P < .001). CONCLUSION: In this study, intranasal ciclesonide, 200 microg once daily, was safe and effective for the long-term treatment of PAR, with no evidence of tachyphylaxis.     

Anti-inflammatory effects of once daily low dose inhaled ciclesonide in mild to moderate asthmatic patients

BACKGROUND: Ciclesonide exhibits clinical efficacy at 160 microg (ex-actuator) once daily but the anti-inflammatory effects at this dose are not known. We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 microg once daily in the morning exhibited significant anti-inflammatory effects. METHODS: Seventeen patients with mild persistent asthma (FEV(1) 3.35 l) were recruited into a double-blind placebo-controlled randomized crossover study. Measurements were made after ciclesonide and placebo treatment as well as after run-in and washout periods, for adenosine monophosphate (AMP) bronchial challenge (primary variable), exhaled nitric oxide (NO) and induced sputum (in a subgroup). RESULTS: The mean (SEM) AMP bronchial challenge PC(20) following ciclesonide (140 (63) mg/ml) was significantly (P < 0.001) increased compared with placebo (17 (8) mg/ml), run-in (13 (5) mg/ml) and washout (9 (3) mg/ml) periods. This amounted to an eightfold (CI: 5.3-12.0) for ciclesonide vs placebo. Likewise, there were significant improvements in exhaled NO levels and a significant reduction in induced sputum eosinophil cell counts. CONCLUSION: We have shown that inhaled ciclesonide given at 160 microg once daily in the morning exhibits significant anti-inflammatory effects that are in keeping with the previously described clinical effects.     

Efficacy of a new 7-day transdermal sequential estradiol/levonorgestrel patch in women

OBJECTIVE: To investigate the efficacy and tolerability of a new 7-day transdermal sequential estradiol/levonorgestrel patch (Fem7 Combi; Merck KGaA; Germany), versus placebo, as hormone replacement therapy in menopausal women. METHODS: A multicentre, randomized, clinical study consisting of a 3-week screening phase, a 12-week double-blind, placebo-controlled treatment phase, and a 12-week open, follow-up phase. Women aged 40-65 years with an intact uterus and menopausal complaints were randomized to either 2 weeks of an estradiol mono patch (50 microg per 24 h) followed by 2 weeks of an estradiol/levonorgestrel combination patch (50 microg/10 microg per 24 h), or a placebo patch, for three 28-day cycles. Changes in the Kupperman Index and the frequency of hot flushes were assessed. RESULTS: The sequential use of a 7-day estradiol patch and a 7-day estradiol/levonorgestrel patch was superior to placebo in reducing menopausal symptoms, and was well tolerated. At the end of the treatment phase, there was a statistically significant reduction in the Kupperman Index score versus placebo (P<0.0001), and a statistically significant difference between groups in the proportion of patients with a reduction in the number of hot flushes (at least 50% versus baseline). During the open follow-up phase, there was a marked reduction in the Kupperman Index score and the number of hot flushes for patients switched from placebo to active study medication. The active medication was effective throughout the 1-week application period. CONCLUSIONS: The new 7-day transdermal sequential estradiol/levonorgestrel patch was well tolerated, providing rapid and effective relief of menopausal symptoms. The addition of low-dose levonorgestrel did not influence the beneficial effects of estradiol.     

Effect of intranasal fluticasone propionate and triamcinolone acetonide on basal and dynamic measures of hypothalamic–pituitary–adrenal-axis activity in healthy volunteers

BACKGROUND : Most published studies show that intranasal corticosteroids have no effect on the hypothalamic-pituitary-adrenal (HPA) axis, but there have been isolated reports to the contrary, contradicting accumulated knowledge on pharmacokinetics. OBJECTIVE : To re-evaluate the effect of fluticasone propionate aqueous nasal spray (FPANS) and triamcinolone acetonide (TAA) aqueous nasal spray on the HPA axis using an improved study design. METHODS : Twenty-three healthy volunteers were randomized in a double-blind, three-way crossover study. The study comprised a 4-day placebo run-in phase followed by three 4-day treatment periods (placebo, FPANS (200 microg once daily) or TAA aqueous nasal spray (220 microg once daily)), separated by 7-14 days washout intervals. Before the first, and on the last day of each treatment period, 12-h overnight urine was collected to assess cortisol excretion and cortisol creatinine ratio. Approximately 26 h after the last administration of study medication, volunteers underwent stimulation with 0.5 microg adrenocorticotropic hormone (ACTH). Serum cortisol concentrations were measured before and 20 and 30 min after injection. Blood and urine samples were analysed for cortisol by liquid chromatography tandem mass spectrometry. RESULTS : Compared with placebo, EP or TAA had no significant effect on mean overnight (12 h) urinary cortisol excretion, and did not significantly suppress the overnight geometric mean urinary cortisol/creatinine excretion ratio. Values for serum cortisol before and after ACTH simulation showed no significant suppression, although there was a slight blunting of the HPA-axis response following TAA treatment. CONCLUSION : This study confirms that there are no detectable effects on the HPA axis following short-term intranasal FP or TAA at their recommended dosages.