Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. Objective: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. Methods: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. Results: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. Conclusions: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.     

Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler.

BACKGROUND: Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma. OBJECTIVE: Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS. METHODS: During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1. RESULTS: Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages. CONCLUSIONS: Once-daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma.     

Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of moderate persistent asthma using fluticasone propionate as an active comparator.

BACKGROUND: Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability. OBJECTIVES: To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research Triangle Park, NC) was used as an active control. DESIGN: A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial. SETTING: Sixty centers in 20 countries. PATIENTS: Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment. INTERVENTIONS: Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 microg twice daily) and one of FP (250 microg twice daily >12 weeks). RESULTS: FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total daily 800-microg dose of MF-DPI conferred no significant additional benefit >400 microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively. CONCLUSIONS: A total daily dose of 400 microg of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 microg of FP Diskhaler.     

Efficacy and safety of mometasone furoate dry powder inhaler vs fluticasone propionate metered-dose inhaler in asthma subjects previously using fluticasone propionate.

OBJECTIVE: To compare the efficacy and safety of mometasone furoate dry powder inhaler (DPI) administered once daily in the evening with fluticasone propionate metered-dose inhaler (MDI) administered twice daily. METHODS: An 8-week, randomized, open-label, parallel-group study compared mometasone furoate DPI, 400 microg every evening (1 puff daily), with fluticasone propionate MDI, two 125-microg puffs twice daily, in 167 adults and adolescents with moderate persistent asthma previously using fluticasone propionate. The primary efficacy variable was the change in forced expiratory volume in 1 second (FEV1) from baseline to the end point. Variables such as response to therapy and subject satisfaction with the inhaler devices were also analyzed. RESULTS: Improvement in FEV1 was noted at the week 2 visit with both treatments. This improvement was maintained at the 4- and 8-week visits and at the end point for both groups. The mean percent change in FEV1 from baseline to the end point was 4.58% with mometasone furoate DPI and 6.98% with fluticasone propionate MDI (P = .35). At the end point, physicians rated 62% of the mometasone furoate DPI group as "improved" or "much improved" compared with 47% of the fluticasone propionate MDI group (P = .007). A significantly greater proportion of subjects in the mometasone furoate DPI group "liked the inhaler a lot" vs subjects in the fluticasone propionate MDI group (46.8% vs 22.4%; P = .01). Both treatments were well tolerated. CONCLUSION: Mometasone furoate DPI, 400 microg every evening, provided comparable efficacy as fluticasone propionate MDI, two 125-microg puffs twice daily, in subjects with moderate persistent asthma previously treated with fluticasone propionate.     

Once-daily evening administration of mometasone furoate in asthma treatment initiation.

BACKGROUND: In a previous study, a 200-microg once-daily evening dose of mometasone furoate dry powder inhaler (DPI) was effective in patients with asthma previously taking inhaled corticosteroids. No studies have been conducted to test the effect of a once-daily evening dose in patients previously using only short-acting beta2-adrenergic agonists (SABAs) for symptom relief. OBJECTIVE: To evaluate the effectiveness of mometasone furoate DPI administered once daily in the evening as initial controller therapy in patients previously using SABAs alone for asthma. METHODS: Patients with mild-to-moderate persistent asthma from 18 US centers participated in a 12-week, randomized, double-blind, placebo-controlled study. Patients received either mometasone furoate DPI, 200 microg, or placebo once daily in the evening. The primary efficacy variable was the change in forced expiratory volume in 1 second from baseline to the end point (last evaluable visit). Other measurements included forced vital capacity, forced expiratory flow between 25% and 75%, morning and evening peak expiratory flow, asthma symptoms, use of albuterol, nocturnal awakenings, physicians' evaluation of response to therapy, and time to asthma worsening. RESULTS: At the end point, the mean increase in forced expiratory volume in 1 second relative to baseline for the mometasone furoate DPI group of 0.43 L (16.8%) was significantly greater than that for the placebo group of 0.16 L (6.0%) (P < .01). Morning peak expiratory flow, forced vital capacity, and forced expiratory flow between 25% and 75% also significantly improved with mometasone furoate DPI treatment relative to placebo (P < .01). Once-daily dosing with mometasone furoate DPI was well tolerated. CONCLUSION: Mometasone furoate DPI (200 microg) administered once daily in the evening significantly improves pulmonary function in patients previously using SABAs alone for asthma control.     

Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma.

BACKGROUND: Flovent Diskus is a powder formulation of the inhaled corticosteroid fluticasone propionate (FP) delivered via a breath-actuated, multidose inhaler. OBJECTIVE: To determine the efficacy and safety of dry powder FP administered once or twice daily (200 microg per day) to children with persistent asthma. METHODS: Twelve-week, randomized, double-blind, placebo-controlled, multicenter trial with a 52-week, open-label extension. Children aged 4 to 11 were required to have pulmonary function 50% to 85% of predicted values. The population was stratified for baseline therapy (inhaled corticosteroid/cromolyn or bronchodilators only). After a 2-week placebo run-in, 242 patients received dry powder FP 200 microg each morning, dry powder FP 100 microg BID, or placebo for 12 weeks; 192 were rerandomized to the QD or BID regimen for an additional 52 weeks of open-label treatment. Primary endpoints were mean changes in FEV1 and morning PEF recorded at clinic visits. RESULTS: Both dry powder FP regimens significantly improved FEV1, evening PEF, and asthma symptoms at the double-blind phase endpoint (P < or = .017 compared with placebo). The BID regimen also significantly improved morning PEF and nighttime awakenings due to asthma (P < or = .005). Among patients previously treated with inhaled corticosteroids/cromolyn, improvements observed with the QD and BID regimens were similar. Patients switched from BID to open-label QD treatment showed additional improvements at week 52 generally comparable to patients who received the BID regimen during both phases. Fluticasone propionate was well tolerated for up to 64 weeks with few reports of drug-related adverse events or morning plasma cortisol abnormalities. CONCLUSIONS: Once daily dosing of dry powder FP 200 microg is an effective and convenient alternative for children whose asthma is controlled with a more frequent dosing regimen of inhaled corticosteroids.     

One-year efficacy and safety of inhaled formoterol dry powder in children with persistent asthma.

BACKGROUND: The long-term efficacy and safety of formoterol dry powder capsules for inhalation in pediatric asthma have not previously been evaluated. OBJECTIVE: We examined the effectiveness of inhaled formoterol over a period of 12 months in asthmatic children who were still symptomatic despite anti-inflammatory treatment. METHODS: After a run-in period, 518 patients (5 to 12 years old) were randomized in a double-blind manner to receive 12 or 24 microg formoterol dry powder (Foradil, Novartis Pharma AG, Basel, Switzerland) or placebo twice daily for 12 months. The drug was administered by inhaler (Aerolizer, Novartis Pharma AG) and was given in addition to their anti-inflammatory treatment. The primary variable was the area under the curve for forced expiratory volume in 1 second measured over 12 hours after the morning dose of study medication. RESULTS: The area under the curve for forced expiratory volume in 1 second after the first dose of treatment and after 3 and 12 months of treatment was significantly greater for patients receiving formoterol 12 microg and 24 microg than for patients receiving placebo (all P < or = 0.0062). Compared with placebo, both doses of formoterol significantly improved morning and evening premedication peak expiratory flow rate (all P < 0.001). In the group treated with formoterol 24 microg, median symptom score and median dose of rescue medication at night were lower than during the run-in period, whereas the opposite occurred in the placebo group. The incidence of hospitalizations for asthma was higher in the formoterol groups than in the placebo group. CONCLUSION: Our results indicate that, in asthmatic children who are still symptomatic despite anti-inflammatory therapy, the addition of formoterol consistently improves airflow obstruction and nocturnal symptoms and reduces the use of rescue medication. However, this treatment requires close disease monitoring to detect early signs of acute exacerbation.     

Clinical benefits of combination treatment with mometasone furoate nasal spray and loratadine vs monotherapy with mometasone furoate in the treatment of seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids and nonsedating antihistamines are the drug classes most often prescribed to treat allergic rhinitis (AR). Treatment guidelines recommend a combination of these agents for moderate-to-severe AR. However, clinical studies have found that combining an antihistamine with an intranasal corticosteroid provides few or no advantages over monotherapy with an intranasal corticosteroid. OBJECTIVE: To compare the efficacy of mometasone furoate nasal spray (NS) plus loratadine with that of monotherapy with the individual agents in patients 12 years and older with at least a 2-year history of seasonal AR. METHODS: In a multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical study, 702 patients were randomized to receive mometasone furoate NS, 200 microg, plus loratadine, 10 mg (n = 169); mometasone furoate NS, 200 microg (n = 176); loratadine, 10 mg (n = 181); or placebo (n = 176) once daily for 15 days. Primary efficacy variables were total nasal symptom score (TNSS) and total symptom score (TSS) as recorded on diary cards. RESULTS: No statistically significant differences were observed between mometasone furoate NS plus loratadine and mometasone furoate NS monotherapy for the primary efficacy variables. For TNSS and TSS, all 3 active drug therapies were more effective than placebo (P < or = .02). Both mometasone furoate NS treatment regimens were more effective than loratadine or placebo for TNSS (P < .01 for both) and TSS (P < or = .03 for both), whereas loratadine was more effective than placebo for TNSS only (P = .02). CONCLUSIONS: Combination therapy with mometasone furoate NS and loratadine provided benefits similar to monotherapy with mometasone furoate NS for the symptoms of seasonal AR. Therefore, mometasone furoate NS monotherapy was shown to be an effective treatment for seasonal AR.     

Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma

BACKGROUND: Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE: We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS: We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS: At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION: MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.     

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   

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.     

Comparison of the bronchodilator effect of salbutamol between pressure metered dosed inhaler and dry powder inhaler in patients with stable bronchial asthma]

Recently, dry powder inhaler (DPI) was more available than pressure metered dosed inhaler (pMDI) for the inhalation therapy of the respiratory disease. But there are differences in the lung deposition of the drug in these devices. We investigated the bronchodilator effect of salbutamol inhalation with two device, pMDI and Tubuhaler on the stable 8 asthmatic patients. The time course of FEV1 had a no significant difference between two devices. DeltaAUC (=difference between area under the curve for time course of increase in FEV1 via pMDI and via DPI) and Deltamax FEV1 (=difference between maximum increases in FEV1 following inhalation of salbutamol via pMDI and DPI) were defined as the index of difference of bronchodilator effect between the two devices. PMDI was more effective on improving the pulmonary function in subjects with severely decreased FEV1 and FEV1% than DPI. These results may reflect the correlation of inspiratory flow rate and drug deposition. PMDI is still useful on the part of asthmatic patients with decreased pulmonary function.     

Beclomethasone dipropionate aerosol compared with dry powder in the treatment of asthma

In a double-blind trial, beclomethasone dipropionate inhaled as a dry powder in doses of 200 μg three times a day was compared with the conventional aerosol of 100 μg three times a day, each for a period of 4 weeks. Neither the dry powder nor the aerosol showed any significant advantage over each other in terms of ventilatory function. Plasma cortisol levels were unaltered with the two medications in spite of the doubled dose of the corticosteroid powder. Choice of one or the other method of administration of medication depended on patient preference and the ease with which he could familiarize himself with either technique.     

A double-blind comparison between a new multi-dose powder inhaler (Turbuhaler®) and metered dose inhaler in children with asthma

Turbuhaler is a ready-loaded multiple dose inhaler which does not require co-ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double-blind cross-over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use.     

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.     

Comparison of the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler on exhaled inflammatory markers in childhood asthma.

BACKGROUND: Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma. OBJECTIVE: To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC). METHODS: In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period. RESULTS: Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment. CONCLUSION: The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.