mometasone-furoate and Asthma

Inhaled corticosteroids (ICS) are known to increase the risk of systemic and local adverse effects, especially with high doses and long-term use. Hence, considerable resources are invested to improve pharmacokinetic/pharmacodynamic (PK/PD) properties of ICS, effective delivery systems and novel combination therapies to enhance the risk-to-benefit ratio of ICS.. There is an unmet need for new solutions to achieve optimal clinical outcomes with minimal dose of ICS. This paper gives an overview of novel treatment strategies regarding the safety of ICS therapy on the basis of the three most recent molecules introduced to our everyday clinical practice - ciclesonide, mometasone furoate, and fluticasone furoate. Advances in aerosol devices and new areas of inhalation therapy are also discussed.. Current progress in improving the risk-to-benefit ratio of ICS through dose and delivery probably established pathways for further developments. This applies both to the improvement of the PK/PD properties of ICS molecules but also includes technical aspects that lead to simplified applicability of the device with simultaneous optimal drug deposition in the lungs. Indubitably, the future of medicine lies not only in the development of new molecules but also in technology and digital revolution.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Drug Therapy, Combination; Humans; Mometasone Furoate

Fixed-dose long-acting beta2-agonist (LABA)/inhaled corticosteroid (ICS) combinations and add-on therapies as needed are the mainstay for maintenance therapy in asthma. However, more than 40% of patients have an inadequately controlled disease. The development of triple fixed-dose combinations consisting of long-acting muscarinic antagonist (LAMA)/LABA/ICS has paved the way for a new approach to reach therapeutic goals of an optimal control of symptoms and an effective prevention of future exacerbations.. A search was conducted on PubMed (MEDLINE), using the MeSH terms [asthma] + [indacaterol] + [glycopyrronium] +[mometasone furoate] + [treatment], until October 2021. Original data from clinical trials, prospective and retrospective studies and reviews were selected. Clinical studies with IND/MF/GLY (Enerzair Breezhaler) are summarized, and its place in current asthma therapy is examined.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Clinical Trials as Topic; Drug Combinations; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Prospective Studies; Quality of Life; Quinolones; Retrospective Studies

Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.. To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.. We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021.. We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.. Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.. Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-rel. Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Topics: Adrenergic beta-2 Receptor Agonists; Asthma; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Quinolones; Receptors, Adrenergic, beta-2

Clinical evidence suggests no clinically relevant pharmacokinetic interactions between indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF). A population pharmacokinetic (popPK) analysis was conducted to identify structural models describing systemic pharmacokinetic profiles of IND, GLY and MF, and estimate the effect of covariates on their pharmacokinetics following inhalation as IND/GLY/MF.. Pharmacokinetic data from 698 patients with asthma were pooled from two Phase III studies that evaluated IND/MF medium- (150/160 µg) and high-dose (150/320 µg), IND/GLY/MF medium- (150/50/80 μg) and high-dose (150/50/160 μg), and a device bridging Phase II study with MF. One popPK model was developed each for IND, GLY and MF using a nonlinear mixed-effect modelling approach. Maximal and trough plasma concentrations were compared across formulations and studies, including data for IND/GLY from chronic obstructive pulmonary disease (COPD) patients. The effect of predefined covariates on the pharmacokinetics of components was evaluated using a full covariate modelling approach.. The final pharmacokinetic models were two-compartment disposition models with first-order elimination and sequential zero-order/first-order absorption (IND), with bolus administration and first-order elimination (GLY), and with mixed zero-order/first-order absorption and first-order elimination (MF). All model parameters were estimated with good precision (% relative standard error: IND and MF ≤25%; GLY <10%). No clinically relevant covariate effect was observed on the pharmacokinetics of IND, GLY and MF. IND and GLY pharmacokinetic profiles were similar across different formulations.. Two-compartment popPK models adequately described the pharmacokinetics of IND, GLY and MF. The effect of covariates was not clinically relevant. The pharmacokinetic profiles of MF were comparable for combination products at corresponding medium- or high-dose inhaled corticosteroids. On a population level, the pharmacokinetics of IND and GLY were comparable between patients with asthma and COPD.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Child; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Combinations; Female; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Models, Biological; Mometasone Furoate; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Young Adult

Once-daily (o.d.) fixed-dose combinations of mometasone furoate/indacaterol acetate (MF/IND) and mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY), both delivered via the Breezhaler® device, are approved for the maintenance treatment of asthma. Across these fixed-dose combinations, while the doses of bronchodilators remain the same, the nominal doses of mometasone furoate in micrograms differ. This article presents the steps followed in bridging the mometasone furoate doses at the corresponding dose strengths in the mometasone furoate formulation delivered via the Twisthaler® and mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulations delivered via the Breezhaler®. These were: (i) bridging the mometasone furoate doses in the Twisthaler® (previously approved) to mometasone furoate doses in the Breezhaler®; (ii) bridging the mometasone furoate doses in the Breezhaler® to mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation. Following this stepwise approach, it was determined that mometasone furoate 80 μg o.d. (medium-dose strength) and 160 μg o.d. (high-dose strength) in mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation provided comparable inhaled corticosteroid efficacy to mometasone furoate 160 μg o.d. (medium-dose strength) and 320 μg o.d. (high-dose strength) in the mometasone furoate/indacaterol acetate formulation, respectively. These doses were used in the PLATINUM Phase III clinical program that investigated the efficacy and safety of mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide combinations in patients with asthma.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Drug Combinations; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Quinolones; Treatment Outcome

Asthma guidelines provide clinicians with evidence-based management strategies for this chronic condition. The preferred therapy for patient with persistent asthma is inhaled corticosteroids. However, ∼40% of the patients with persistent asthma continue to present with symptoms while treated according to the guidelines. Multiple factors are being explored to explain the variability in response to inhaled corticosteroids including asthma phenotype and genetic predisposition among others. The nonatopic asthma phenotype has been described in the literature. These patients tend to have milder symptoms of asthma and typically outgrow their asthma by adolescence. They present with chronic asthma symptoms in the absence of a positive allergy test, either skin prick test or specific immunoglobulin E blood test. Although patients with nonatopic asthma share many characteristics with patients with atopic asthma, there are several studies that suggest a different inflammatory pathway may be involved in their pathophysiology. Therefore, it is possible that children with nonatopic asthma could respond differently to inhaled corticosteroids compared with those with atopic asthma. Currently there is a variable definition of this phenotype. Furthermore, there is a paucity of therapeutic trial directed toward the patients with nonatopic asthma specifically. Future research should be guided toward identifying the inflammatory pathways in nonatopic asthma and potential phenotype-guided therapies.

Topics: Allergy and Immunology; Anti-Asthmatic Agents; Asthma; Bronchi; Child; Chronic Disease; Diagnosis, Differential; Gastroesophageal Reflux; Humans; Mometasone Furoate; Practice Guidelines as Topic; Proton Pump Inhibitors; Respiratory Mucosa; Respiratory Sounds; Tiotropium Bromide; Treatment Outcome

For the last three decades, the guidelines for asthma management have supported a stepwise therapeutic approach, based on the administration of controller medications (especially inhaled corticosteroids) complemented by on-demand use of rescue medication. Classically, the rescue medication recommended comprised short-acting β agonists (SABA). Some years ago, the use of Symbicort Maintenance and Reliever Therapy (SMART) demonstrated the benefits of a combination of budesonide-formoterol, an inhaled corticosteroid, and a long-acting β agonist (ICS-LABA) as rescue medication in moderate and severe asthma. The results were enthusiastically received, and this therapeutic option was adopted in the guidelines for moderate to severe asthma patients. Recently, four trials (two randomised placebo control trials under the auspices of the SYGMA project and two real-life studies, Novel START, and the PRACTICAL trial) have explored the potential benefits of substituting SABA with budesonide-formoterol as rescue medication in mild asthma patients. The SYGMA 1 and 2 studies showed that the combination with formoterol-budesonide as rescue medication provides better asthma control than short-acting β-agonists alone in GINA step 2 patients, although the superiority was slight. Compared to budesonide maintenance therapy, the fixed combination of ICS-LABA on demand provides poorer asthma control. Regarding exacerbations, the fixed dose ICS-LABA combination on demand showed the same benefits for the prevention of exacerbations as chronic ICS treatment in mild asthma patients. The Novel START study, which assessed a population with milder symptoms, concluded that the fixed dose ICS-LABA combination used as needed was superior to SABA (albuterol) as needed for the prevention of asthma exacerbations. These results in fact show that, in undertreated GINA step 2 with only SABA as needed, ICS-LABA is more effective than SABA. The authors of PRACTICAL concluded that the study provided modest evidence that the ICS-LABA combination used as-needed for symptom relief reduces the rate of severe exacerbations compared with maintenance low-dose budesonide plus terbutaline as needed, although the study was not limited to mild asthma since according to the treatment consumed, it was evident that they had recruited some moderate asthma patients. Despite this poor evidence, and ignoring the clinical histological benefits of chronic inhaled corticosteroids (especially when administered promptly)

Topics: Administration, Inhalation; Adrenergic beta-Antagonists; Asthma; Humans; Mometasone Furoate; Tiotropium Bromide

Topics: Asthma; Budesonide, Formoterol Fumarate Drug Combination; Eosinophils; Humans; Mometasone Furoate; Sputum; Tiotropium Bromide

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child Development; Child, Preschool; Fluticasone; Glucocorticoids; Humans; Infant; Mometasone Furoate; Pregnenediones

Asthma is a common respiratory disease characterized by airway inflammation, bronchoconstriction and airway hyperresponsiveness and symptoms such as coughing, wheezing, shortness of breath and chest tightness. Allergic rhinitis is a common comorbidity in asthma and glucocorticoids are the key stone in the treatment of both diseases. Mometasone furoate is a potent synthetic steroid with a very high receptor affinity and a low bioavailability and shown to be superior compared to other inhaled corticosteroids. It is not clear whether the use of mometasone furoate nasal spray (MFNS) is associated with an improvement in asthma control.. This current paper reviews the current knowledge on the effect of mometasone furoate nasal spray in the treatment of asthma and includes clinical trials in which both subjective and objective outcomes are assessed.. To date, only few clinical studies have investigated the effect of nasal steroids in the treatment of asthma. The studies investigating the effect of MFNS report contradicting results, although the most well-designed study to answer this question finds no improvement in asthma control. Thus, it seems unlikely that asthma guidelines will be influenced by the current knowledge on the effect of MFNS in the treatment of asthma.

Topics: Administration, Intranasal; Anti-Allergic Agents; Asthma; Glucocorticoids; Humans; Mometasone Furoate; Nasal Sprays; Treatment Outcome

Pressurized metered dose inhalers (pMDIs) are evolving to be a very effective drug delivery option in patients with airway diseases. They offer comparable lung deposition and reduced oropharyngeal deposition similar with the dry powder inhalers. As recommended by the Global Initiative for Asthma guidelines, the ideal maintenance treatment for asthma is a combination of long acting β2-agonists (LABAs) and inhaled corticosteroids (ICSs). One of the available LABA/ICS combinations is the salmeterol/fluticasone propionate combination (SFC) and a plethora of evidence supports its clinical efficacy and safety.. This article focuses on the SFC hydrofluroalkane pMDI and compares the efficacy and tolerability with salmeterol and fluticasone given individually, and with other fixed-dose combinations namely formoterol/fluticasone, formoterol/beclometasone and formoterol/mometasone furoate, all delivered via pMDI. Also discussed is the efficacy and tolerability of the SFC delivered via a pMDI, as compared to the SFC via Diskus.. pMDIs play an important role in inhalation therapy given the low price, low maintenance and convenience of use. LABA/ICS combinations are the preferred choice of medication for asthma treatment and will remain the mainstay for the decades to come. In our opinion, pMDI should be the choice of device to administer LABA/ICS maintenance therapy, as it is already being used by the patients for reliever therapy, which may eventually improve patient adherence and compliance.

Topics: Albuterol; Androstadienes; Asthma; Beclomethasone; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Lung; Metered Dose Inhalers; Mometasone Furoate; Pregnadienediols

Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth.. To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment).. We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014.. Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma.. Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child.. We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) [corrected] given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%.Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi² = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated li. Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Patient Dropouts; Pregnadienediols; Pregnenediones

Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians.. To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma.. We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014.. Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma.. Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation.. Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X(2) = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision.. In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Pregnadienediols; Pregnenediones; Randomized Controlled Trials as Topic

Long-term corticosteroid use may increase cataract risk. The Lens Opacities Classification System (LOCS) III ranked lens opacities as Class 1: 0.5-0.9 unit; Class 2: 1.0-1.4 units; or Class 3: ≥1.5 units in clinical trials of combined mometasone furoate and formoterol (MF/F) administered by metered-dose inhaler (MDI). We examined retrospectively shifts in lenticular opacity in patients with chronic obstructive pulmonary disease (COPD) or asthma.. We analyzed pooled LOCS III data from two COPD studies and separately analyzed LOCS III data from an asthma study. COPD subjects were randomized to twice daily MF/F 200/10 μg, MF/F 400/10 μg, MF 400 μg, F 10 μg, and placebo; asthma subjects were randomized to MF/F 200/10 μg, MF/F 400/10 μg, fluticasone propionate/salmeterol (FP/S) 250/50 μg, and FP/S 500/50 μg. Lenticular opacity changes were analyzed post hoc for proportions of subjects with LOCS III grade increases ≥0.5, ≥1.0, or ≥1.5 units at weeks 26 and 52.. Proportions of subjects in the COPD studies with Class 1 (≥0.5 unit), 2 (≥1.0 unit), or 3 (≥1.5 units) increases in LOCS III at week 26 (N = 1675) ranged from 15.5 to 18.6%, 3.3-6.0%, and 0.9-2.2%, respectively. At week 52 (N = 1085), proportions of active-treated subjects with Class 1, 2, or 3 increases in LOCS III ranged from 26.6 to 28.9%, 6.3-10.7%, and 2.6-5.9%, respectively. Treatment differences in lenticular shifts were generally small and nonsignificant in the asthma study.. No clinically relevant trends were observed in the LOCS III assessment of lenticular shifts during treatment of COPD and asthma patients, although further study may be needed to confirm the findings presented here. In these trials, MF/F effects on lens opacity were not observed. (Clinicaltrials.gov numbers: NCT00383435, NCT00383721, and NCT00379288.).

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Cataract; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Multicenter Studies as Topic; Pregnadienediols; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Severity of Illness Index

It has been of great interest whether mometasone furoate (MF) is better than other inhaled corticosteroids (ICSs) as the controller therapy in patients with moderate or severe asthma who had previously been taking ICSs.. The aim of this meta-analysis is to thoroughly compare the efficacy and safety of MF versus other ICSs with equipotent daily doses in those patients.. Relative databases were searched. Randomised controlled trials of more than or equal to 4 weeks' treatment duration comparing MF with other ICSs were reviewed.. Six trials with 1354 randomised patients met the inclusion criteria. Significant differences favouring MF were found in all indices of pulmonary function. MF was superior compared to other ICSs in decreasing the frequency of rescue medication use and morning difficulty breathing score. There was no significant difference between MF and other ICSs therapy in morning wheezing score, cough score and percentage of patients with no nocturnal awakenings due to asthma. For the treatment-related adverse effects (AEs), treatment-related severe AEs, discontinuations due to AEs and some common symptom of AEs, MF was all similar to other ICSs in their incidence.. In adult patients with moderate or severe asthma who had previously been taking ICSs, MF was superior to other ICSs with equipotent daily doses as controller monotherapy in improving pulmonary function and decreasing the frequency of rescue medication use, and was similar to other ICSs in the incidence of AEs. These results demonstrated the priority of MF in asthma therapy.

Topics: Administration, Inhalation; Asthma; Humans; Mometasone Furoate; Odds Ratio; Pregnadienediols; Respiratory Function Tests; Steroids; Treatment Outcome

Asthma is a common chronic respiratory disease affecting the airways causing inflammation, airway hyperreactivity (AHR), and respiratory symptoms. Frequently, asthma can be effectively treated with inhaled corticosteroids (ICS) but in more severe cases additional drugs are required, such as long-acting β2-agonists (LABA). Mometasone furoate (MF) is a synthetic steroid exhibiting a strong affinity for the glucocorticoid receptor as well as a low bioavailability and a high plasma protein binding. In most cases, MF only requires once daily administration. Formoterol fumarate (F) is a full β2-agonist with a rapid onset and 12 h of duration.. The present paper reviews the current knowledge of the novel combination of MF and F for the treatment of asthma. Furthermore, a description of the individual components is included.. At present, only few clinical studies of MF/F are available for review and more studies of MF/F efficacy are needed, especially comparative studies on other ICS/LABA drugs. However, it does not appear from the reviewed literature that MF/F or its individual components are inferior to other equivalent treatments.

Topics: Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Mometasone Furoate; Pregnadienediols

The corticosteroid mometasone and the long-acting β(2)-selective adrenoreceptor agonist formoterol have been combined in a single pressurized metered-dose inhaler for use in patients aged ≥12 years with asthma. In a 26-week well designed trial in patients with persistent asthma uncontrolled on medium-dose inhaled corticosteroids (ICS), mometasone/formoterol 200 μg/10 μg twice daily (bid) was more effective than placebo or the same nominal dosage of formoterol alone in reducing the incidence of asthma deteriorations, as well as in improving lung function, asthma control, asthma symptoms and asthma-related quality-of-life outcomes. The combination was also more effective than the same nominal dosage of mometasone alone in improving lung function and asthma control. Similarly, in a 12-week well designed trial in patients with persistent asthma uncontrolled on high-dose ICS, mometasone/formoterol 400 μg/10 μg bid was more effective than the same nominal dosage of mometasone alone in improving lung function, asthma control and asthma symptoms. Treatment with a lower dosage of the combination (200 μg/10 μg bid) yielded similar results and, moreover, significantly reduced the incidence of asthma deteriorations compared with mometasone alone. Mometasone/formoterol was generally well tolerated in clinical trials of 12-52 weeks' duration. The adverse event profile of the combination was consistent with that of its individual components; no new or unexpected safety signals were detected.

Topics: Adrenergic beta-2 Receptor Agonists; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Metered Dose Inhalers; Mometasone Furoate; Pregnadienediols; Randomized Controlled Trials as Topic; Severity of Illness Index

Asthma is a chronic inflammatory disease that causes significant morbidity and mortality. Inhaled corticosteroids are the preferred initial treatment for this disorder. Mometasone furoate dry powder is an inhaled corticosteroid that is approved for once-daily treatment of asthma in both adults and children as young as 4 years.. The goal of this paper is to review the clinical efficacy and safety of mometasone furoate dry powder inhaler for the treatment of asthma. A literature search using PubMed was done using the terms 'mometasone furoate', 'inhaled corticosteroid' and 'asthma', focusing on articles that highlighted clinical trials and addressed efficacy of the medication.. Mometasone furoate dry powder inhaler has an excellent safety and efficacy profile. For patients with persistent asthma who require treatment with an inhaled corticosteroid, mometasone furoate is an excellent therapeutic choice.

Topics: Anti-Inflammatory Agents; Asthma; Dry Powder Inhalers; Humans; Mometasone Furoate; Pregnadienediols; Quality of Life

Mometasone furoate and formoterol fumarate dihydrate (MF/F) administered via metered-dose inhaler with a dose counter is a new fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist indicated for daily maintenance therapy in patients aged ≥12 years with persistent asthma. Randomized, controlled trials have suggested that MF/F reduces asthma deteriorations while improving lung function and other measures of asthma control, including quality-of-life. Clinical safety studies lasting up to 1 year have found that MF/F has a low incidence of local and systemic side effects.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Lung; Metered Dose Inhalers; Mometasone Furoate; Pregnadienediols; Treatment Outcome

Inhaled corticosteroids (ICSs) are effective controller medications that treat the chronic inflammation of asthma. The goal of asthma treatment is to improve lung function, symptoms, and the ability to perform daily activities, while decreasing the risk of exacerbations. Mometasone furoate delivered via a dry powder inhaler (MF-DPI) is indicated for once-daily maintenance treatment of asthma in patients as young as 4 years old.. To review the quality of evidence for the clinical efficacy and safety of MF-DPI in both adults and children in the context of grading systems for guideline recommendations. Publications were identified by searching PubMed (MEDLINE) for 'mometasone furoate AND dry powder inhaler AND asthma' in any field with search limits for publications from 1 January 1995 to 1 August 2008.. MF-DPI has been evaluated in 21 randomized, double-blind, active- or placebo-controlled trials in adults with asthma. Clinical trials investigating the efficacy in patients previously treated with only short-acting beta(2)-agonists, other ICSs, or oral corticosteroids revealed that MF-DPI is efficacious in these populations. The results of a pooled analysis of ten trials and individual results of three long-term safety trials indicate that MF-DPI is well-tolerated with minimal adverse events. Six clinical trials of MF-DPI have been completed in children. Studies of pediatric patients treated with approved doses of MF-DPI indicate that children previously maintained on twice-daily treatment of other ICSs showed improvements in lung function, health-related quality of life, and rescue medication use. In addition, there is no effect on growth velocity or the hypothalamic-pituitary-adrenal axis. In both adults and children, once-daily dosing of MF-DPI has been demonstrated to be as efficacious as twice-daily dosing.. The findings of this single-database review are that once-daily MF-DPI is efficacious and safe in both adults and children with asthma.

Topics: Administration, Inhalation; Adolescent; Anti-Allergic Agents; Asthma; Child; Child, Preschool; Humans; Mometasone Furoate; Nebulizers and Vaporizers; Pregnadienediols; Randomized Controlled Trials as Topic; Treatment Outcome

The high prevalence of asthma in pediatric patients underscores the need for effective and safe treatment in this population. Current treatment guidelines recommend inhaled corticosteroids (ICSs) as a preferred treatment for the control of mild to moderate persistent asthma in patients of all ages, including young children. Clinical efficacy, systemic safety, and ease of use are desirable attributes of an ICS used to treat children with persistent asthma. Recently, mometasone furoate administered via a dry powder inhaler (MF-DPI) 110 microg once daily in the evening (delivered dose of 100 microg) was approved by the US FDA for the maintenance treatment of asthma in children 4-11 years of age. Data from the clinical trial program for MF-DPI that establish the efficacy, long-term safety, and absence of systemic effects of the approved dosage in children with mild to moderate persistent asthma are reviewed. These findings indicate that once-daily dosing of MF-DPI in children aged 4-11 years significantly improves lung function and health-related quality of life while reducing rescue medication use and exacerbations despite previous treatment with other ICSs. MF-DPI is also well tolerated in children. Clinical trial results showed that, at the approved dosage, there are no effects on growth velocity or the hypothalamic-pituitary-adrenal axis. Results of pediatric studies are consistent with the clinical development program for adults and adolescents. In addition, once-daily dosing, established safety, and ease of use of MF-DPI may help to improve asthma management by addressing issues that inhibit proper adherence.

Topics: Adrenal Cortex Hormones; Asthma; Child; Clinical Trials as Topic; Humans; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols

Inhaled corticosteroids (ICS) are recommended as a controller medication in the most recent Global Initiative for Asthma and the National Heart, Lung and Blood Institute guidelines. Mometasone furoate (MF) is an effective, well-tolerated inhaled steroid and is indicated for the maintenance treatment of adult and adolescent patients (> or = 12 years) with persistent asthma. MF is approved for once or bid maintenance treatment of asthma (in patients previously receiving ICS or bronchodilators). Low systemic bioavailability and high relative binding affinity for the glucocorticoid receptor are properties of MF that allow for a favourable efficacy and tolerability profile. Inhaled MF has been shown to be an effective and well-tolerated controller medication for those patients with mild, moderate or severe persistent asthma. MF has recently been approved by the US regulatory authorities for use in children (4-11 years). Future developments include the combination of MF with the long-acting bronchodilators, formoterol and indacaterol, to provide additional options in the treatment of asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biological Availability; Child; Child, Preschool; Humans; Middle Aged; Mometasone Furoate; Pregnadienediols; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Mometasone furoate has been available for clinical use, starting with a dermatologic preparation, for nearly 20 years. An inhaled format of the drug for management of asthma had been in development during the last decade and has been available for clinical use for 6 years as a dry powder inhaler delivering either 100 mcg or 200 mcg per dose. It has a long half-life and is suitable for daily dosing. The drug is approved for use in the USA for the treatment of asthma in patients aged 4 years or over. Mometasone furoate is a topically potent glucocorticoid with a favorable risk-benefit profile. A wide variety of randomized clinical trials have shown the drug to have a clinically beneficial effect on asthma comparable to fluticasone propionate, and to permit the reduction or withdrawal of oral glucocorticoid therapy in patients with asthma. Mometasone furoate has approximately 1% oral bioavailability but does produce systemic glucocorticoid effects from the drug released from the lung and its metabolites. These effects are minimal when mometasone is used appropriately at low or moderate doses.

Topics: Administration, Inhalation; Adult; Anti-Allergic Agents; Asthma; Biological Availability; Child; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols

To examine the evidence for the efficacy of once daily dosing of mometasone furoate (MF) and to establish the dose-response relationship for MF in asthma.. Meta-analysis of double-blind, randomized controlled clinical trials, identified through a Medline and EMBASE search, comparing once versus twice daily dosing with the same dose and/or comparing two different doses that presented data on measurements of clinical efficacy. Main outcome measures were FEV(1) change from baseline, PEF, withdrawals for any reason and treatment failure as defined by the authors.. Nine studies with 2533 subjects were identified, although not all had usable data for the different doses/schedules. There was no evidence of superiority of twice versus once daily dosing of MF with a pooled difference of 0.02 L (95% CI: -0.06-0.10) for FEV(1) change from baseline. 400 microg was superior to 200 microg with a pooled difference of 0.09 L (95% CI: 0.04-0.13) for FEV(1). Data on doses >400 microg/day were limited but did not support that 800 microg was superior to 400 microg.. For the outcome variables considered, once daily dosing of MF is as effective as twice daily dosing, which may be useful in improving compliance in the treatment of asthma. There was insufficient data to compute a dose-response curve for MF.

Topics: Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Mometasone Furoate; Pregnadienediols; Treatment Outcome

Results from two clinical trials of mometasone furoate administered via a dry powder inhaler (MF-DPI) were reviewed to evaluate the consistency of effects of MF-DPI administered once-daily in the evening (QD PM) or twice-daily (BID) on health-related quality of life (HRQOL) in adults with persistent asthma previously treated with inhaled corticosteroids. HRQOL data were collected from two 12-week, randomized, double-blind trials: in study 1 (n = 268), patients received MF-DPI 400 microg QD PM (1 inhalation), MF-DPI 200 microg BID, or placebo; in study 2 (n = 400), patients received MF-DPI 200 microg QD PM, MF-DPI 400 microg QD PM (1 inhalation), MF-DPI 200 microg BID, MF-DPI 400 microg QD PM (2 inhalations of 200 microg), or placebo. In both studies, HRQOL was assessed using the Medical Outcomes Survey 36-item Short Form (SF-36) and an asthma-specific module. MF-DPI was associated with consistent, statistically significant improvements in asthma-specific total scores, breathlessness, asthma concerns, and physical symptoms compared with placebo in both trials (p < 0.05 vs. placebo). MF-DPI improved SF-36 Physical Component Summary scores at all doses except 200 microg QD PM. In conclusion, the results from two placebo-controlled trials suggest that MF-DPI 400 microg/d, administered once or twice-daily, produces consistent, statistically, and clinically significant improvement in HRQOL measures in patients with persistent asthma.

Topics: Activities of Daily Living; Anti-Allergic Agents; Asthma; Humans; Interpersonal Relations; Mental Health; Mometasone Furoate; Nebulizers and Vaporizers; Pregnadienediols; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index

Mometasone furoate (MF), a potent synthetic inhaled corticosteroid (ICS) with a high affinity for the glucocorticoid receptor, is approved for use in the treatment of asthma.. Publications reviewed in this article were identified via searches of MEDLINE and EMBASE databases using the terms 'mometasone furoate AND pharmacology' and 'mometasone furoate AND asthma AND clinical trial'. Data from abstracts presented at respiratory society meetings, and relevant background information, are also reviewed.. In clinical studies, MF, administered by dry powder inhaler (MF-DPI), was effective in treating all severities of persistent asthma, improving pulmonary function, reducing asthma symptoms, and reducing or eliminating the need for oral corticosteroids. Once-daily dosing of MF-DPI was effective in patients with mild or moderate persistent asthma previously taking twice-daily regimens of inhaled corticosteroids (ICSs), and in patients taking only inhaled beta2-agonists for symptom relief. Once-daily dosing in the evening with MF-DPI 200 microg conferred a greater benefit than morning dosing with MF-DPI 200 microg. Patients with severe asthma who were dependent on oral corticosteroids (OCSs) and high doses of ICSs were able to achieve greater asthma control and reduce or even eliminate OCSs when switched to MF-DPI. In trials of up to 1 year in duration, MF-DPI was well tolerated, with the majority of adverse events considered mild or moderate in intensity. MF had low systemic bioavailability and no clinically significant hypothalamic-pituitary-adrenal-axis suppression at therapeutic doses. The DPI device is a multiple-dose inhaler with a counter containing agglomerates of MF and lactose. Patients of all severities of persistent asthma were able to generate and maintain airflow profiles necessary to provide a uniform and accurate dose.. Only one study evaluated both morning and evening administration of once-daily doses, and one of the comparative clinical trials was an open-label study.. Once-daily administration of MF-DPI 200-400 microg in patients with mild to moderate persistent asthma effectively improved lung function and asthma control. In patients with severe persistent asthma dependent on oral corticosteroids, treatment with MF-DPI 400 microg BID permitted substantial reduction of oral corticosteroid use. All MF-DPI treatments were well tolerated and had minimal systemic effects.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Humans; Mometasone Furoate; Pregnadienediols; Treatment Outcome

Mometasone furoate dry-powder inhaler (MF-DPI) is an inhaled corticosteroid (ICS) used for the treatment of persistent asthma in patients aged >or= 12 years. MF-DPI has low systemic bioavailability and high glucocorticoid receptor affinity compared with most other ICSs and modifies inflammatory mediators involved in the pathogenesis of asthma. MF-DPI, unlike other available ICSs, is approved for initiation as a once-daily in the afternoon (q.d. PM) regimen. Studies show that MF-DPI 200 or 400 microg q.d. PM treatment significantly improves lung function and symptom control in patients with mild, moderate or severe asthma. MF-DPI 400 microg q.d. PM is reported to be equivalent to fluticasone propionate 250 microg b.i.d. and beclometasone dipropionate 168 microg b.i.d. and more efficacious than budesonide 400 microg, b.i.d. or q.d. MF-DPI is generally well tolerated, with minimal effects on the hypothalamic-pituitary-adrenal axis.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Humans; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols

Inhaled mometasone furoate (Asmanex) is a synthetic corticosteroid indicated for the first-line maintenance prophylactic therapy of persistent asthma in adults and adolescents. It is formulated for delivery via a breath-actuated dry powder inhaler (DPI) [Twisthaler].Inhaled mometasone furoate delivered by DPI is effective in treating patients with persistent asthma. It improves pulmonary function and health-related quality of life, reduces symptoms and decreases oral corticosteroid requirements in severe disease. It is a potent anti-inflammatory agent and is at least as clinically effective as other inhaled corticosteroids. Inhaled mometasone furoate is equally effective in controlling asthma when administered in two divided doses or as a single daily dose. Once-daily administration of mometasone furoate 200 microg in the evening was more effective than administration of the same dosage in the morning. The drug is well tolerated, with low systemic bioavailability and minimal systemic activity. Therefore, it is an effective and convenient option for controller therapy of persistent asthma in adults and adolescents.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Chronic Disease; Humans; Mometasone Furoate; Pregnadienediols; Quality of Life

Inhaled corticosteroids are the gold standard of daily therapy for effective control of all stages of persistent asthma. For this review of the new inhaled corticosteroid mometasone furoate, a MEDLINE/PubMed search using the terms "mometasone furoate AND asthma" found 57 articles, 17 of which presented data from efficacy and safety studies reviewed herein. In clinical trials, once-daily evening dosing of mometasone furoate delivered via dry powder inhaler (200 or 400 mu g/day) was effective in patients with mild to moderate asthma previously treated with short-acting beta2-agonists alone and in those previously maintained on inhaled corticosteroid therapy. In patients with severe asthma, mometasone furoate 400 mu g twice daily eliminated or reduced the need for oral prednisone while improving lung function, asthma symptoms, and quality of life. Clinical studies have shown that mometasone furoate is generally well tolerated and has minimal systemic activity at recommended doses. In conclusion, mometasone furoate provides primary care and specialty physicians with a safe, effective, and convenient option to meet the challenges of asthma management.

Topics: Anti-Asthmatic Agents; Asthma; Humans; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols; Treatment Outcome

Inhaled corticosteroids (ICS) are the mainstay of asthma therapy. Although compliance to this type of medication is often suboptimal and once-daily dosing can help to improve adherence to the treatment, the clinical implications of such a mode of administration should be determined.. This review summarizes the recent studies on comparative efficacy of once-versus twice-daily administration of ICS, in light of previous reports.. Although twice-daily administration of ICS is often better to optimize asthma parameters, in many patients, asthma can be sufficiently controlled by a once-daily regimen of most ICS. An increased frequency of dosing seems preferable if asthma becomes uncontrolled or is severe, although this requires further study. A therapeutic trial should, however, be done to ensure that asthma control is adequate. Comparative long-term effects of such a strategy on inflammatory and remodeling parameters remain to be determined, as does the proportion of patients who can adequately control their asthma with once-daily administration of the various ICS available.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols; Treatment Outcome

Asthma is characterized by inflammation in the lung and glucocorticoids (GCs) are the most clinically effective treatment available. The success of chronic GC therapy for asthma stems largely from the ability of the GC-GC receptor (GR) complex to alter transcription of a wide array of molecules involved in the inflammatory process. Many of the adverse effects of elevated systemic GC levels have been reduced through the use of inhalation as a method of administration, as opposed to oral GC. GCs exert their effects by binding to the wild-type GR, GR(alpha). The GR(alpha) complex can directly or indirectly alter gene transcription by binding to specific DNA sites or by activating transcription factors. There is also evidence to support GR(alpha) involvement in post-translational activities. In the management of asthma, the GR(alpha) down-regulates proinflammatory mediators such as interleukin-(IL)-1, 3, and 5, and up-regulates anti-inflammatory mediators such as IkappaB [inhibitory molecule for nuclear factor kappaB1 IL-10, and 12. Newer GCs are being designed to increase potency and topical activity. Mometasone furoate (MF), has recently been developed for the treatment of asthma and inhibits key anti-inflammatory processes with a potency equal to or greater than that of fluticasone propionate. A better understanding of the molecular mechanisms involved might provide strategies for optimizing the effectiveness of GC in the treatment of asthma.

Topics: Anti-Inflammatory Agents; Asthma; Cytokines; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols; Receptors, Glucocorticoid; Transcription, Genetic

Mometasone furoate is a corticosteroid with relatively high in vitro potency. Recent randomised, double-blind, multicentre trials have assessed the efficacy of mometasone furoate delivered by dry powder inhaler over 12 weeks in adults and adolescents with mild to severe persistent asthma. Mometasone furoate 200 microg twice daily or 400 microg once daily in the morning or 200 microg once daily in the evening improved lung function, asthma symptom scores and use of rescue medication to a significantly greater extent than placebo in patients who had previously received only short-acting inhaled beta2-adrenoceptor agonists alone as treatment in 3 trials (n = 195 to 306). In studies in 227 to 733 patients with mild to moderate asthma who were receiving ongoing treatment with inhaled corticosteroids prior to enrolment, mometasone furoate 100 to 400 microg twice daily was consistently better at improving the above indicators of asthma than placebo. Mometasone furoate 100 to 200 microg twice daily was as effective as beclomethasone dipropionate 200 microg twice daily or budesonide 400 microg twice daily and mometasone furoate 200 microg twice daily was as effective as fluticasone propionate 250 microg twice daily. Mometasone furoate 400 or 800 microg twice daily was also consistently more effective than placebo in reducing oral corticosteroid dosages and improving lung function and asthma symptoms in 132 patients with oral corticosteroid-dependent asthma. Once daily administration of mometasone furoate 400 microg appears to be as effective at improving indicators of asthma as twice daily administration of 200 microg. Patients receiving mometasone furoate < or =800 microg/day and recipients of placebo experienced a similar overall incidence of adverse events considered to be related to treatment. The most common of these events were oral candidiasis, headache, pharyngitis and dysphonia. Mometasone furoate 100 to 400 microg twice daily, beclomethasone dipropionate 200 microg twice daily, budesonide 400 microg twice daily or fluticasone propionate 250 microg twice daily were similarly tolerated.. Inhaled mometasone furoate is well tolerated, with minimal systemic activity and is equally effective when administered as a divided dose or as a single daily dose. Use of the drug can result in a decrease in requirements for oral corticosteroids in patients with oral corticosteroid-dependent asthma and is as effective as other inhaled corticosteroids currently used in the treatment of mild to moderate persistent asthma. Thus mometasone furoate is suitable for the control of mild to severe persistent asthma in adults or adolescents.

Topics: Administration, Inhalation; Adolescent; Adult; Animals; Anti-Inflammatory Agents; Asthma; Cytochrome P-450 Enzyme System; Cytokines; Humans; Mometasone Furoate; Pregnadienediols

The 52-week long-term safety of once-daily indacaterol acetate/glycopyrronium bromide/mometasone furoate (IND/GLY/MF) high-dose (150/50/160 µg) and IND/MF high-dose (150/320 µg) was evaluated in two studies enrolling Japanese patients with inadequately controlled asthma.. Study 1 (IND/GLY/MF) and Study 2 (IND/MF) were 52-week, phase III, open-label, single-arm, multicenter studies conducted in Japanese adult patients with inadequately controlled asthma. The primary endpoint was incidence and severity of treatment-emergent adverse events (AEs) over 52-weeks.. In Study 1, 94 patients received IND/GLY/MF high-dose and 84 (89.4%) patients completed the 52-week study treatment; in Study 2, 51 patients received IND/MF high-dose and 48 (94.1%) patients completed the 52-week study treatment. In Study 1, 68.1% and 6.4% of 94 patients reported ≥1 AE and ≥1 serious AE (SAE) respectively. In Study 2, 78.4% of 51 patients reported ≥1 AE; no patients reported SAEs. The most commonly reported AEs were asthma (exacerbation; 30.9% and 54.9%) and nasopharyngitis (18.1% and 29.4%) in Study 1 and Study 2, respectively. Severe AEs including asthma (exacerbation) were reported in 13.8% and 13.7% of patients in Study 1 and Study 2, respectively. In Study 1, 10 patients (10.6%) reported treatment-related AEs, of which dysphonia (9 patients [9.6%]) was the most commonly reported; no treatment-related AEs were reported in Study 2. In Study 1, one death (not study drug-related) was reported after study discontinuation (92 days after last dose of study medication).. Once-daily IND/GLY/MF and IND/MF high-dose were well-tolerated in Japanese patients with inadequately controlled asthma. No unexpected safety findings were observed.. Supplemental data for this article is available online at.

Topics: Acetates; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchodilator Agents; Drug Combinations; East Asian People; Glycopyrrolate; Humans; Mometasone Furoate; Treatment Outcome

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with asthma, particularly of late onset. Current treatment options for CRSwNP have limitations, and there is an unmet need for other safe and effective therapies.. The aim of the THUNDER study was to determine the efficacy and safety of the prostaglandin D. THUNDER was a phase 3b, randomized, multicenter, double-blind, placebo-controlled, parallel-group, 16-week study of fevipiprant 150 mg or 450 mg once daily versus placebo. All patients received intranasal mometasone furoate 200 μg daily.. Ninety-eight patients were randomly assigned to fevipiprant 150 mg (n = 32), fevipiprant 450 mg (n = 34), or placebo (n = 32). Mean (SE) change from baseline in nasal polyp score at week 16 was 0.20 (0.224) for fevipiprant 150 mg, -0.10 (0.216) for fevipiprant 450 mg, and 0.14 (0.233) for placebo. Mean treatment difference was 0.05 (95% confidence interval, -0.59, 0.70; adjusted P = .979) for fevipiprant 150 mg versus placebo and -0.25 (95% confidence interval, -0.88, 0.39; adjusted P = .656) for fevipiprant 450 mg versus placebo. There was no meaningful difference in the secondary end points for fevipiprant versus placebo.. THUNDER provided no evidence of a role for fevipiprant in the treatment of patients with CRSwNP and asthma; future studies may establish a role for other DP

Topics: Asthma; Chronic Disease; Double-Blind Method; Humans; Indoleacetic Acids; Mometasone Furoate; Nasal Polyps; Pyridines; Rhinitis; Sinusitis; Treatment Outcome

Chronic rhinosinusitis with nasal polyps (CRSwNP) and type 2 asthma share the same inflammatory pathophysiology and are frequent comorbidities. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin 4 and interleukin 13, which are key and central drivers of type 2 inflammation.. We report the effect of dupilumab vs placebo on outcome measures of the upper and lower airways and health-related quality of life (HRQoL) in the pooled population of patients with CRSwNP and comorbid asthma from the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies.. In these randomized, double-blind, placebo-controlled trials, patients received subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks on a background of mometasone furoate nasal spray. Changes from baseline at week 24 in the upper and lower airway outcome measures are reported.. Of the 724 patients randomized, 428 (59.1%) had comorbid asthma. In patients with asthma at week 24, dupilumab vs placebo improved the nasal polyp score (-2.04), patient-reported nasal congestion score (-1.04), Lund-Mackay computed tomography scan score (-6.43), peak nasal inspiratory flow (46.15 L/min), and 22-item sinonasal outcome test score (-21.42; all P < .001). The forced expiratory volume in 1 second and 6-item asthma control questionnaire scores were also markedly improved with dupilumab vs placebo. The most common adverse events (nasopharyngitis, headache, injection-site erythema, worsening of nasal polyposis, and asthma) were more frequent with placebo than dupilumab.. Dupilumab improved upper and lower airway outcome measures and HRQoL in patients with severe CRSwNP and comorbid asthma and was well tolerated.. ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52).

Topics: Adult; Antibodies, Monoclonal, Humanized; Asthma; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Interleukin-4 Receptor alpha Subunit; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Placebos; Quality of Life; Receptors, Interleukin-13; Rhinitis; Sinusitis; Surveys and Questionnaires; Young Adult

QMF149 is an inhaled fixed-dose combination of indacaterol acetate and mometasone furoate (MF) delivered via Breezhaler®, under development for once-daily treatment of asthma. MF delivered via Twisthaler® is approved as Asmanex® Twisthaler® for the treatment of asthma. Bridging of MF delivered via Twisthaler® to MF delivered via Breezhaler® was undertaken as part of QMF149 development to enable dose comparisons between the devices. Pharmacokinetics (PK) of MF were characterized in two studies; a single dose PK study in healthy volunteers and a pharmacokinetic/pharmacodynamic (PK/PD) study in asthma patients.. The PK study in healthy volunteers evaluated the PK of single doses of MF via Breezhaler® (50-400 μg) and compared systemic exposure of MF following administration via Breezhaler® and Twisthaler® 400 μg (2 inhalations of 200 μg). The study in patients with asthma characterized the MF PK profile following once-daily inhalation of MF via Breezhaler® and Twisthaler® devices for 4 weeks.. In the open-label, single-dose, crossover study, healthy subjects sequentially received MF via Twisthaler® (400 μg, medium-dose inhaled corticosteroid [ICS]) and escalating doses via Breezhaler® (50, 100, 200, 400 μg). PK data were obtained up to 72 h post-dose. In the double-blind, double-dummy, parallel-group study, asthma patients were randomised to receive either MF 80 μg (low-dose ICS) or 320 μg (high-dose ICS) via Breezhaler®, or 200 μg (low-dose ICS) or 800 μg (2 inhalations of 400 μg; high-dose ICS) via Twisthaler® once daily for 4 weeks. PK sampling was performed on Days 1 and 28 at pre-dose and up to 24 h post-dose.. In the healthy volunteer PK study, 20 healthy subjects completed all treatments. Dose-normalised AUC. PK characterization in a healthy volunteer PK study and subsequently an asthma study enabled selection of 80 μg (low), 160 μg (medium), and 320 μg (high) delivered via Breezhaler® as MF doses comparable to the 200 μg, 400 μg and 800 μg doses delivered by Twisthaler®, respectively, as part of QMF149 formulation development.

Topics: Administration, Inhalation; Asthma; Cross-Over Studies; Double-Blind Method; Dry Powder Inhalers; Humans; Mometasone Furoate; Pregnadienediols

Because of historical safety concerns with the use of long-acting β-agonists (LABA) in asthma, step-down from inhaled corticosteroid (ICS)/LABA combination therapy to ICS monotherapy is recommended once asthma control is achieved.. To evaluate the benefit/risk question about whether patients with asthma who achieve disease control on fixed-dose ICS/LABA combination therapy, such as mometasone furoate/formoterol fumarate (MF/F), should continue with this therapy or be stepped down to ICS monotherapy, such as MF.. Using data from 8447 clinically stable patients with persistent asthma in the Safety Pharma Investigation of Respiratory Outcomes trial who had been receiving a stable dose of ICS/LABA for ≥4 weeks, this post hoc analysis evaluated the risk of serious asthma outcomes (SAOs) (adjudicated hospitalization, intubation, or death) and asthma exacerbation (AEX) (composite of hospitalizations ≥24 hours, emergency visits <24 hours requiring systemic corticosteroid, or systemic corticosteroid for ≥3 consecutive days) in participants randomized to remain on ICS/LABA (MF/F) or step down to ICS (MF) for 26 weeks.. There was no significant difference in SAO risk among patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (hazard ratio [HR], 1.03 [95% confidence interval (CI): 0.61, 1.75], P = .913). The risk of AEX was significantly lower in patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (HR, 0.87 [95% CI: 0.78, 0.98], P = .020).. In this post hoc analysis of a large clinical trial dataset, maintenance on ICS/LABA with MF/F is not associated with an increased risk of SAOs and also significantly reduces the risk of AEX compared with step-down from ICS/LABA to MF.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Drug Therapy, Combination; Formoterol Fumarate; Humans; Mometasone Furoate

Asthma affects over 6 million children in the United States alone. This study investigated the efficacy and long-term safety of mometasone furoate-formoterol (MF/F) and MF monotherapy in children with asthma.. This phase 3, multicenter, randomized controlled trial evaluated metered-dose inhaler twice daily (BID) dosing with MF/F 100/10 µg or MF 100 µg in children, aged 5 to 11 years, with a history of asthma for greater than or equal to 6 months and confirmed bronchodilator reversibility, who were adequately controlled on inhaled corticosteroid/long-acting beta-agonist combination therapy for greater than or equal to 4 weeks. After a 2-week run-in on MF 100 µg BID, eligible patients received 24 weeks of double-blind treatment and were followed for safety up to 26 weeks. The primary efficacy endpoint was the change from baseline in AM postdose 60-minute AUC %predicted FEV1% across 12 weeks of treatment.. A total of 181 participants received at least one dose of MF/F (n = 91) or MF (n = 90). MF/F was superior to MF across the 12-week evaluation period, with a treatment advantage of 5.21 percentage points (P < .001). Superior onset of action with MF/F over MF was achieved as early as 5 minutes postdose on day 1. Overall, approximately 50% of participants experienced one or more treatment-emergent adverse events, with fewer occurring in the MF/F group.. In children 5 to 11 years of age with persistent asthma, the addition of F to MF was well tolerated and provided significant, rapid, and sustained improvement in lung function compared with MF alone.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Mometasone Furoate; Nebulizers and Vaporizers; Spirometry; Treatment Outcome

Global initiative for asthma (GINA) 2019 recommends adding a long-acting β. This phase III QUARTZ was a multicentre, randomised, double-blind, double-dummy and parallel-group study to assess the efficacy and safety of low-dose IND/MF 150/80 μg once daily (o.d.) versus MF 200 μg o.d. in adult and adolescent patients with inadequately controlled asthma.. Eligible patients (n = 802) were randomised (1:1) to receive either low-dose IND/MF 150/80 μg o.d. via Breezhaler® or MF 200 μg o.d. via Twisthaler® for 12 weeks. Primary endpoint was trough forced expiratory volume in 1 s (FEV. These results support the use of low-dose IND/MF 150/80 μg o.d. as a potential therapy for adult and adolescent patients with inadequately controlled asthma.

Topics: Administration, Inhalation; Adult; Asthma; Drug Combinations; Female; Forced Expiratory Volume; Humans; Indans; Male; Middle Aged; Mometasone Furoate; Quality of Life; Quinolones; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Indans; Male; Middle Aged; Mometasone Furoate; Quinolones; Young Adult

Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting β. This 52-week, double-blind, triple-dummy, parallel-group, phase 3 study recruited patients from 316 centres across 24 countries. Patients aged 12 to 75 years with a documented diagnosis of asthma for at least 1 year, percentage of predicted FEV. Between Dec 29, 2015, and May 4, 2018, 2216 patients were randomly assigned (high-dose MF-IND, n=445; medium-dose MF-IND, n=439; high-dose MF, n=442; medium-dose MF, n=444; high-dose FLU-SAL, n=446), of which 1973 (89·0%) completed the study treatment and 234 (10·6%) prematurely discontinued study treatment. High-dose MF-IND (treatment difference [Δ] 132 mL [95% CI 88 to 176]; p<0·001) and medium-dose MF-IND (Δ 211 mL [167 to 255]; p<0·001) showed superiority in improving trough FEV. Once-daily FDC of ICS and LABA (MF-IND) significantly improved lung function over ICS monotherapy (MF) at week 26; high-dose MF-IND was non-inferior to twice-daily combination of ICS and LABA (high-dose FLU-SAL) for improvement in trough FEV. Novartis Pharmaceuticals.

Topics: Adolescent; Adult; Aged; Asthma; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Indans; Male; Middle Aged; Mometasone Furoate; Quinolones; Treatment Outcome; Young Adult

Patients with asthma who are inadequately controlled on inhaled corticosteroid-long-acting β. In this 52-week, double-blind, double-dummy, parallel-group, active-controlled phase 3 study, patients were recruited from 415 sites across 41 countries. Patients aged 18 to 75 years with symptomatic asthma despite treatment with medium-dose or high-dose ICS-LABA, at least one exacerbation in the previous year, and a percentage of predicted FEV. Between Dec 8, 2015, and Jun 14, 2019, 3092 of 4851 patients screened were randomly assigned (medium-dose MF-IND-GLY, n=620; high-dose MF-IND-GLY, n=619; medium-dose MF-IND, n=617; high-dose MF-IND, n=618; high-dose FLU-SAL, n=618). 2747 (88·8%) patients completed the 52-week treatment and 321 (10·4%) started but discontinued study treatment prematurely. Medium-dose MF-IND-GLY (treatment difference [Δ] 76 mL [95% CI 41-111]; p<0·001) and high-dose MF-IND-GLY (Δ 65 mL [31-99]; p<0·001) showed superior improvement in trough FEV. Once-daily, single-inhaler MF-IND-GLY improved lung function versus ICS-LABA combinations (MF-IND and FLU-SAL) in patients with inadequately controlled asthma. The safety profile was similar across treatment groups. MF-IND-GLY therefore constitutes a good treatment option in these patients.. Novartis Pharmaceuticals.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Mometasone Furoate; Muscarinic Antagonists; Nebulizers and Vaporizers; Quinolones; Treatment Outcome; Young Adult

School-supervised use of a once-daily inhaled corticosteroid regimen (supervised therapy) can improve medication adherence and asthma control.. We sought to evaluate the effectiveness of supervised therapy in a unique setting and population.. We conducted a cluster randomized trial of supervised therapy in 20 elementary schools with a disproportionate enrollment of low-income Latino students. Schools were purposively selected, matched, and randomized to receive 9 months of supervised therapy with mometasone furoate or usual care. All English- or Spanish-speaking students with self-reported asthma were eligible. The Asthma Control Questionnaire (ACQ) was interviewer administered quarterly at school. Students in supervised therapy schools were hypothesized to have lower ACQ scores than students in usual-care schools.. Of 393 enrolled students, 189 students receiving immediate intervention and 143 students receiving delayed intervention provided 1 or more ACQ data points, were between 6 and 10 years of age, and were included in the primary analysis. At baseline, 39% of students reported taking a controller medication, and 24% had well-controlled asthma. Eighty percent of students receiving immediate intervention were prescribed mometasone. Schools administered 98% of prescribed doses when students attended school. Absences, weekends, and holidays reduced calendar adherence to 53%. During the first year, the mean ACQ score for students receiving immediate and delayed intervention was 1.55 (95% CI, 1.41-1.70) and 1.64 (95% CI, 1.47-1.80), respectively. The estimated treatment effect was -0.08 (95% CI, -0.31 to 0.14).. Compared with usual care, supervised therapy did not improve asthma control among this population of Latino students. Additional research is warranted to confirm these results.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child; Female; Humans; Male; Medication Adherence; Mometasone Furoate; Poverty; School Health Services; Schools; Surveys and Questionnaires; United States

The safety of long-acting β-agonists added to inhaled corticosteroids for the treatment of persistent asthma has been controversial.. We sought to determine whether administering formoterol in combination with mometasone furoate increases the risk of serious asthma outcomes (SAOs) compared with mometasone furoate alone. This clinical trial is registered as NCT01471340.. We conducted a 26-week, randomized, double-blind trial in adolescent and adult patients (≥12 years) with persistent asthma in 35 countries with the primary objective of evaluating whether mometasone furoate-formoterol increases the risk of SAOs (adjudicated hospitalization, intubation, or death) compared with mometasone furoate alone. The key efficacy end point was asthma exacerbation (composite of hospitalization of ≥24 hours, emergency department visits of <24 hours requiring systemic corticosteroids, or use of systemic corticosteroids for ≥3 consecutive days).. Among 11,729 patients (mometasone furoate-formoterol, n = 5,868; mometasone furoate, n = 5,861), a total of 81 SAOs, all asthma-related hospitalizations, were observed in 71 patients: 45 events from 39 patients receiving mometasone furoate-formoterol and 36 events from 32 patients receiving mometasone furoate. The hazard ratio for the first SAO in the mometasone furoate-formoterol versus mometasone furoate group was 1.22 (95% CI, 0.76-1.94; P = .411). Asthma exacerbation occurred in 1,487 patients: 708 receiving mometasone furoate-formoterol and 779 receiving mometasone furoate. The hazard ratio for the first asthma exacerbation in the mometasone furoate-formoterol versus mometasone furoate group was 0.89 (95% CI, 0.80-0.98; P = .021).. The addition of formoterol to mometasone furoate maintenance therapy did not increase the risk of serious asthma-related events and reduced the risk of asthma exacerbation.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Humans; Male; Middle Aged; Mometasone Furoate; Mometasone Furoate, Formoterol Fumarate Drug Combination; Symptom Flare Up; Young Adult

Inhaled mometasone was shown to improve pain scores and decrease soluble vascular cell adhesion molecule (sVCAM) concentration in a randomized controlled trial of nonasthmatic patients with sickle cell disease. We sought to explore potential changes in systemic inflammation as a mechanism underlying this effect. Serum samples from 41 trial participants (15 placebo- and 26 mometasone-treated) were analyzed using a 92 inflammatory marker panel at baseline and after 8 weeks of mometasone therapy. Individual marker analysis and correlation analysis were conducted. Adjusted for age, the mometasone-treated group decreased the concentration of CXCL9, CXCL11, CD40, IL-10, and IL-18 relative to placebo-treated participants. Hierarchical clustering and correlation analysis identified additional evidence for a decrease in cytokines linking to macrophage signaling and migration. There was no statistically significant change in markers of asthma and allergy, indicating that the improvement was unlikely mediated by modulation of occult reactive airway disease. This analysis of inflammatory markers suggests that decrease in macrophage activity may be involved in the mediation of the clinical benefit seen with use of inhaled mometasone in nonasthmatic patients with sickle cell disease.Trial registration: clinicaltrials.gov identifier: NCT02061202.

Topics: Administration, Inhalation; Adult; Anemia, Sickle Cell; Asthma; Biomarkers; CD40 Antigens; Chemokine CXCL11; Chemokine CXCL9; Female; Humans; Interleukin-10; Interleukin-18; Macrophages; Male; Middle Aged; Mometasone Furoate; Pain

In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown.. In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level.. A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P = 0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P = 0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%).. The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level. (Funded by the National Heart, Lung, and Blood Institute; SIENA ClinicalTrials.gov number, NCT02066298.).

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Glucocorticoids; Humans; Leukocyte Count; Male; Medication Adherence; Middle Aged; Mometasone Furoate; Sputum; Tiotropium Bromide; Young Adult

Sinonasal disease can contribute to poor asthma control. There are reports that link obesity with an increased prevalence of sinonasal disease, but no studies evaluating the severity of sinonasal disease in obese asthmatics, and how this impacts asthma control. The purpose of the current study was to determine if obesity is associated with increased severity of sinonasal disease, and/or affects response to nasal corticosteroid treatment in asthma.. This study included 236 adults participating in a 24-week randomized, double-masked, placebo-controlled study of nasal mometasone for the treatment of poorly controlled asthma. Sinonasal disease severity was assessed using validated questionnaires, and compared in participants of differing BMIs. Eosinophilic inflammation was assessed using markers in nasal lavage, serum and exhaled nitric oxide. Response to treatment was compared in different BMI groups.. Obesity had no effect on the severity of sinonasal disease symptoms in asthmatics (Sino-Nasal Outcome Test 22 (SNOT 22) score [mean ± SD] 35.4 ± 18.5, 40.2 ± 22.8, and 39.1 ± 21.7, p = 0.43, in lean, overweight and obese participants), nor on nasal, bronchial or systemic markers of allergic inflammation. Nasal steroids had some limited effects on symptoms, lung function and inflammatory markers in lean participants, but no detectable effect was found in obese patients.. Obesity does not affect severity of sinonasal disease in patients with asthma; the association of sinonasal disease symptoms with increased asthma severity and markers of Type 2 inflammation are consistent across all BMI groups. The response of obese patients to nasal corticosteroids requires further study.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nose Diseases; Obesity; Respiratory Function Tests; Severity of Illness Index; Young Adult

Mometasone furoate (MF), delivered via dry-powder inhaler (DPI) QD in the evening (PM), is a treatment option for pediatric patients with asthma. We evaluated MF delivered via a metered-dose inhaler (MDI), in children ages 5-11 years with persistent asthma.. This was a 12-week double-blind, double-dummy, placebo-controlled trial. Pateints were randomized to the following treatments: MF-MDI 50 mcg BID, MF-MDI 100 mcg BID, MF-MDI 200 mcg BID, MF-DPI 100 mcg QD PM, and placebo. The primary analysis assessed MF-MDI doses versus placebo, on the change in %-predicted forced expiratory volume in one second (FEV. For change from baseline in %-predicted FEV. In children ages 5-11 years with persistent asthma, all three doses of MF-MDI (50, 100, and 200 mcg BID) demonstrated significant improvement in FEV

Topics: Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Least-Squares Analysis; Male; Metered Dose Inhalers; Mometasone Furoate

Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases.. To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis.. A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up.. Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks.. Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety.. Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95% CI, -1.0 to 0.4) with placebo and -1.9 (95% CI, -2.5 to -1.2) with dupilumab (LS mean difference, -1.6 [95% CI, -2.4 to -0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95% CI, -11.1 to -6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 [95% CI, -25.6 to -10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%).. Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.. clinicaltrials.gov Identifier: NCT01920893.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Interleukin-13; Interleukin-4; Least-Squares Analysis; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Quality of Life; Sinusitis

Chronic sinonasal disease is common in asthmatic patients and associated with poor asthma control; however, there are no long-term trials addressing whether chronic treatment of sinonasal disease improves asthma control.. We sought to determine whether treatment of chronic sinonasal disease with nasal corticosteroids improves asthma control, as measured by the Childhood Asthma Control Test and Asthma Control Test in children and adults, respectively.. A 24-week multicenter, randomized, placebo-controlled, double-blind trial of placebo versus nasal mometasone in adults and children with inadequately controlled asthma was performed. Treatments were randomly assigned, with concealment of allocation.. Two hundred thirty-seven adults and 151 children were randomized to nasal mometasone versus placebo, and 319 participants completed the study. There was no difference in the Childhood Asthma Control Test score (difference in change with mometasone - change with placebo [ΔM - ΔP], -0.38; 95% CI, -2.19 to 1.44; P = .68; age 6-11 years) or the Asthma Control Test score (ΔM - ΔP, 0.51; 95% CI, -0.46 to 1.48; P = .30; age ≥12 years) in those assigned to mometasone versus placebo. In children and adolescents (age 6-17 years) there was no difference in asthma or sinus symptoms but a decrease in episodes of poorly controlled asthma defined by a decrease in peak flow. In adults there was a small difference in asthma symptoms measured by using the Asthma Symptom Utility Index (ΔM - ΔP, 0.06; 95% CI, 0.01 to 0.11; P < .01) and in nasal symptoms (sinus symptom score ΔM - ΔP, -3.82; 95% CI, -7.19 to -0.45; P = .03) but no difference in asthma quality of life, lung function, or episodes of poorly controlled asthma in adults assigned to mometasone versus placebo.. Treatment of chronic sinonasal disease with nasal corticosteroids for 24 weeks does not improve asthma control. Treatment of sinonasal disease in asthmatic patients should be determined by the need to treat sinonasal disease rather than to improve asthma control.

Topics: Administration, Intranasal; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Child; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Mometasone Furoate; Paranasal Sinuses; Pregnadienediols; Quality of Life; Respiratory Function Tests; Treatment Outcome

To investigate the safety and efficacy of QMF149, a once-daily, fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol maleate and inhaled corticosteroid (ICS) mometasone furoate (MF) for the treatment of persistent asthma. The hypothesis was that QMF149 would not increase the risk of serious asthma exacerbations.. 174 research centres in nine countries.. 1519 adolescents and adults with persistent asthma who were treated or qualified for treatment with combination LABA/ICS were randomised, and 1508 were included in the intention-to-treat analysis.. Patients were randomised to QMF149 (indacaterol maleate 500 µg/MF 400 µg) or MF (400 µg) once daily via Twisthaler inhalation device in a double-blind, parallel-group study for 6-21 months.. The primary end point was time to first serious asthma exacerbation (resulting in hospitalisation, intubation or death). The key secondary end point was annual rate of exacerbations requiring systemic corticosteroids.. Treatment with QMF149 resulted in no significant difference in time to first serious exacerbation compared to MF (2 (0.3%) vs 6 events (0.8%); difference -0.52 percentage point; 95% CI -1.25 to 0.21, p=0.160, HR=0.31; 95% CI 0.06 to 1.54, p=0.151). QMF149 significantly reduced the annual rate of exacerbations requiring systemic corticosteroids (rate ratio=0.71; 95% CI 0.55 to 0.90, p=0.005). Proportions of patients experiencing adverse events were similar across groups (74.0% in the QMF149 group and 73.4% in the MF group). Serious adverse events occurred in 4% and 5.8% of patients in the QMF149 and MF groups, respectively.. No significant difference was observed in the primary outcome of time to first serious asthma exacerbation in patients treated with QMF149 compared with patients treated with MF. Long-term treatment with QMF149 once daily had a favourable safety/efficacy profile in adolescent and adult patients with persistent asthma.. ClinicalTrials.gov; NCT00941798.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indans; Male; Maleates; Middle Aged; Mometasone Furoate; Pregnadienediols; Quinolones; Young Adult

The bronchodilatory effect of mometasone furoate/formoterol fumarate (MF/F) administered by metered-dose inhaler (MDI) with or without a spacer has not been evaluated previously in children aged 5-11 years.. This was a randomized, multicenter, placebo-controlled, single-dose, four-period crossover study. Children with persistent asthma aged 5-11 years participated in this study. Subjects used inhaled corticosteroids with/without long-acting beta-2 agonists for 12 weeks before enrollment and at screening had forced expiratory volume in 1 sec (FEV1 ) ≥70% predicted. Subjects received MF/F MDI 100/10 µg with/without spacer (AeroChamber Plus® with Flow-Vu® Anti-Static Valved Holding Chamber), F-Dry Powder Inhaler (F-DPI) 10 µg, and placebo MDI with/without spacer in separate treatment periods. The primary endpoint was FEV1 area under the curve from 0 to 12 hr (AUC0-12hr ) for the comparison of MF/F with spacer versus placebo. Secondary measurements included MF/F without spacer versus placebo, as well as MF/F with spacer versus MF/F without spacer, and F-DPI versus placebo. Analysis was performed with an analysis of covariance model for a crossover study.. Data from 87 subjects were analyzed. MF/F with spacer demonstrated a larger change in mean FEV1 AUC0-12hr versus placebo (115 vs. -9 mL), with a treatment difference of 124 mL (95% CI 94-154, P < 0.001). Similarly, MF/F without spacer versus placebo resulted in a 102 mL difference in mean-adjusted FEV1 AUC0-12hr (95% CI 73-131, P < 0.001), whereas the difference between MF/F with spacer versus MF/F without spacer was 22 mL (95% CI -8 to 52, P = 0.144). The difference between F-DPI versus placebo was 106 mL (95% CI 77-135, P < 0.001). No unexpected adverse events were observed.. In this trial, MF/F MDI 100/10 µg demonstrated significant bronchodilation in children aged 5-11 years regardless of the use of a spacer. No difference in bronchodilation was observed between MF/F MDI and F-DPI.

Topics: Anti-Inflammatory Agents; Area Under Curve; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cross-Over Studies; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Mometasone Furoate; Pregnadienediols; Treatment Outcome

A well-controlled study in patients with allergic asthma was warranted to assess dose-dependency between fractional concentration of exhaled nitric oxide (FeNO) and sputum eosinophils to a combination of an inhaled corticosteroid plus a long-acting β2-agonist. We sought to characterize the dose-dependency of mometasone furoate/formoterol (MF/F) using FeNO and sputum eosinophil percentage as surrogates of airway inflammation in subjects with allergic asthma.. Following a 2-week, open-label run-in, 93 subjects (≥12 y) using only short-acting beta agonist reliever medication as needed, were randomized to twice daily (BID) placebo; MF/F 100/10 μg, 200/10 μg, or 400/10 μg (via pressurized metered-dose inhaler [MDI]); MF-MDI 200 μg; or MF 200 μg via dry powder inhaler (DPI) during a 2-week, double-blind treatment period.. All active treatments demonstrated significant percentage reductions from baseline in FeNO compared with placebo at all time points (P ≤ 0.034). At endpoint, mean MF/F treatment group FeNO reductions ranged from -35.3% to -61.4%. Sputum eosinophil percentage reductions from baseline were significant compared with placebo for the MF/F 200/10 μg, MF/F 400/10 μg, and MF-DPI 200 μg groups at endpoint (P ≤ 0.023). Escalating MF/F doses significantly reduced both FeNO (P ≤ 0.001) and sputum eosinophil (P ≤ 0.022) levels in a dose-dependent manner at all time points. All treatments were well tolerated; no serious adverse events were observed.. All 3 MF/F doses demonstrated pronounced, clinically meaningful, dose-dependent reductions in FeNO, with reduced sputum eosinophil levels for MF/F 200/10 μg and MF/F 400/10 μg. These findings suggest both inflammatory markers may be useful in assessing corticosteroid responsiveness in asthma patients, and perhaps identifying the same asthma subphenotype. Clinical Trials.gov: NCT00635882.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Breath Tests; Bronchodilator Agents; Circadian Rhythm; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Eosinophils; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Leukocyte Count; Male; Middle Aged; Mometasone Furoate; Nitric Oxide; Peak Expiratory Flow Rate; Pregnadienediols; Sputum; Treatment Outcome; Young Adult

The effects of mometasone furoate and fluticasone propionate on the hypothalamic-pituitary-adrenal axis were compared when administered from combination metered-dose inhaler (MDI) products.. In a randomized, open-label, placebo-controlled, parallel group study, 66 patients with mild to moderate asthma received one of the following four treatments bid through an MDI for 42 days: mometasone furoate/formoterol (MF/F) 200 μg/10 μg, MF/F 400 μg/10 μg, fluticasone propionate/salmeterol (FP/S) 460 μg/42 μg, or placebo. Plasma cortisol concentrations were measured over 24 h on days -1 (baseline) and 42. Geometric mean ratio (GMR) and 90% CI for mean change from baseline to day 42 in 24-h plasma cortisol area under the curve (AUC) were calculated for each treatment. If the 90% CI for the GMRs fell within 70% to 143%, treatments were deemed comparable.. Mean baseline cortisol AUCs were similar across groups. Mean cortisol effects (change from baseline) were similar for MF/F 400 μg/10 μg and FP/S 460 μg/42 μg (GMR, 119%; 90% CI, 101%-140%). Effects of MF/F 200 μg/10 μg on cortisol AUC were similar to placebo (GMR, 92%; 90% CI, 78%-110%), whereas MF/F 400 μg/10 μg and FP/S 460 μg/42 μg lowered cortisol AUC vs placebo (GMR, 78% [90% CI, 66%-92%] and 66% [90% CI 56%-78%], respectively). All treatments were generally well tolerated.. MF/F 400 μg/10 μg or FP/S 460 μg/42 μg bid through an MDI led to similar reductions from baseline in mean cortisol AUC (22% and 34% lower than placebo, respectively), whereas the effect of MF/F 200 μg/10 μg was similar to placebo.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Pituitary-Adrenal System; Pregnadienediols; Treatment Outcome; Young Adult

This study evaluated the effect of mometasone furoate (MF)/formoterol (F) versus its monocomponents, each administered via metered-dose inhaler, on asthma deteriorations and lung function. This 26-week, multicentre, double-blind, placebo-controlled study included subjects aged ≥12 yrs with not well-controlled asthma on low-dose inhaled corticosteroids. After a 2-3-week open-label run-in (MF 100 μg b.i.d.), 746 subjects were randomised to receive placebo, F 10 μg, MF 100 μg or MF/F 100/10 μg b.i.d. Co-primary end-points were time to first asthma deterioration (MF/F versus F to assess effect of MF) and change in forced expiratory volume in 1 s (FEV(1)) area under the curve of serial spirometry measurements over the 12-h period following the morning dose (AUC(0-12h)) (baseline to week 12; MF/F versus MF to assess effect of F). The therapeutic effect of MF in the combination was demonstrated by a reduction in asthma deterioration incidence with MF/F versus F and a delayed time to first asthma deterioration (p<0.001). Asthma deterioration incidence was also reduced with MF/F versus MF (p=0.006). The therapeutic effect of F in the combination was demonstrated by MF/F versus MF in FEV(1) AUC(0-12h) change (4.00 versus 2.53 L·h, respectively; p=0.001). MF/F treatment also resulted in a marked improvement in health-related quality of life. MF/F 100/10 μg b.i.d. treatment showed greater clinical efficacy than its individual components or placebo; both components contributed to the efficacy of MF/F.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Disease Progression; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Quality of Life; Respiratory Function Tests; Sleep; Treatment Outcome; Young Adult

Rhinosinusitis and polyposis are difficult to treat in patients with Samter's triad; they commonly recur despite sinus surgery, antibiotics, and/or nasal steroids. The present study assesses the efficacy of a multimodal regimen that includes topical corticosteroids and antibiotics delivered through a hydroxyethyl cellulose gel and by nebulization.. Eleven patients with Samter's triad who had polyposis and rhinosinusitis that recurred despite endoscopic sinus surgery were treated with a 6-week course of multimodal topical therapy consisting of a hydroxyethyl cellulose gel that releases corticosteroids and antibiotics, topical nebulization of corticosteroids and antibiotics, saline solution rinses, and sinus debridement. Clinical outcomes were evaluated by Lund-Kennedy endoscopic and symptom scores. Histologic assessment was evaluated by hematoxylin and eosin staining before and after treatment.. Both Lund-Kennedy symptom and endoscopic scores showed.a progressive and statistically significant decline throughout the course of treatment, reaching at 6 weeks 42% of the pretreatment values (p = 0.005) for the Lund-Kennedy symptom score and 34% (p = 0.002) for the endoscopic score, respectively; however, the significance of the improvement was lost with time.. Topical gel therapy improves clinical symptoms, endoscopic findings, and sinus membrane histologic features in patients with refractory Samter's triad, but the improvement is transient, suggesting that a longer therapeutic period might be needed.

Topics: Administration, Topical; Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Aspirin; Asthma; Debridement; Drug Hypersensitivity; Endoscopy; Female; Gels; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Pregnadienediols; Rhinitis; Sinusitis; Syndrome; Treatment Outcome

Allergic rhinitis, especially when persistent (PER) and associated with asthma heavily impairs patients' quality of life (QoL).. This study assessed the effect of mometasone furoate nasal spray (MFNS) on the QoL of patients with PER and asthma, using the Rhinasthma questionnaire (EUDRACT n. 2007-004683-45).. Patients with moderate/severe PER and intermittent asthma were randomized to MFNS (alcohol-free) 200 μg/day or placebo for 28 days. Rhinasthma was completed at baseline and at weeks 2 and 4. The total five symptom score (T5SS) for rhinitis, the asthma symptom score and the sum of the two [global symptoms score (GSS)] were recorded daily. The primary outcome was the change in the Rhinasthma global summary (GS) at the end of treatment. Secondary end-points were (a) the change from baseline to end of treatment of each Rhinasthma factor: upper airways (UAs), lower airways (LAs) and respiratory allergy impact; (b) the change from baseline to end of treatment of the T5SS and of the GSS and (c) the use of rescue medication.. Fifty-two adults were randomized. Compared with placebo, MFNS produced a significant change in the Rhinasthma GS (-10.4 vs. 0.4; P<0.01). MFNS also achieved a significant improvement of the UA (-16.6 vs. 0.1; P<0.001), LA (-10.8 vs. 1.1; P<0.001) and GSS (-6.7 vs. -3.1; P=0.019). The change of the T5SS was greater in the MFNS group but did not reach statistical significance.. In patients with PER rhinitis and intermittent asthma, MFNS improves the QoL and the burden of respiratory symptoms. Treating rhinitis may affect the asthma-related QoL.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Allergic Agents; Asthma; Double-Blind Method; Female; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Quality of Life; Rhinitis, Allergic, Perennial; Surveys and Questionnaires; Young Adult

To date, there is limited psychometric evidence on the Asthma Quality of Life Questionnaire (AQLQ12 +) among populations that include adolescents and adults.. To provide evidence of the psychometric properties of the AQLQ12+ as a measure of asthma-specific quality of life (QOL) in patients with persistent asthma treated with a combination of inhaled glucocorticoid and long-acting beta2-agonist, as well as explore the predictors of at least a minimally important AQLQ12+ improvement.. The psychometric properties of the AQLQ12+ were assessed through post hoc analysis of two large (n = 740 and 778) Phase III, randomized, double-blinded, placebo-controlled efficacy studies of mometasone furoate/formoterol fumarate (MF/F) combination compared with monotherapy in subjects with persistent asthma previously treated with either low-dose or medium-dose inhaled glucocorticoids.. With 15% and 8% participation from 12- to 17-year olds, blinded trial data demonstrated excellent reproducibility (ICC range: 0.76-0.85) and moderate-to-strong construct validity with other measures of asthma health at baseline and over time for the AQLQ12 +. A greater percentage of the MF/F treatment group (44%) achieved an important change at 26 weeks on the AQLQ12+ compared with formoterol fumarate (F, 23%) and placebo (18%) treatment groups in the low-dose study (P < 0.001) and the medium-dose study (50% (MF/F) versus 34% (F) and 23% (placebo); P < 0.001). Pre-randomization nighttime awakenings and rescue medications use were significant predictors of AQLQ12+ improvement.. These findings provide strong support for the measurement properties of the AQLQ12+ among patients with persistent asthma and confidence in the AQLQ12+ improvements demonstrated by the MF/F treatment group.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Inflammatory Agents; Asthma; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Health Status Indicators; Humans; Logistic Models; Male; Mometasone Furoate; Pregnadienediols; Psychometrics; Quality of Life; Surveys and Questionnaires; Young Adult

The effects of adding a second inhaled corticosteroid with a different particle size, compared with using an increased dose of a single inhaled corticosteroid, were assessed in patients with persistent asthma.. This was an open-label study of Japanese asthma patients over 20 years of age. After a 1-month run-in period, 36 patients with inadequate control while using salmeterol/fluticasone propionate 50/250 µg (SFC50/250) bd, were randomized to receive SFC50/500 bd or SFC50/250 plus mometasone 100 µg bd (SFC50/250/MF100) for 2 months.. Both treatments resulted in improvements in morning and evening PEF. There were no significant changes in FEV(1) , maximum mid-expiratory flow, maximum expiratory flow rate at 50%, maximum expiratory flow rate at 25% or exhaled NO (FENO) in the SFC50/500 group. On the other hand, there were significant improvements in FEV(1) % (+12.2%, P = 0.0142), %maximum mid-expiratory flow (+28.9%, P = 0.0181), %MEF50 (+32.4%, P = 0.0206) and %MEF25 (+30.3%, P = 0.0113) in the SFC50/250/MF100 group. The changes in FENO (-23.2% (P = 0.0157) in the SFC50/250/MF100 group and -14.5% (not significant) in the SFC50/500 group) did not differ significantly between the groups.. In patients with severe persistent asthma, addition of low-dose mometasone to SFC50/250 improved spirometric parameters, FENO and PEF, while an increase in dose from SFC50/250 to SFC50/ 500 only improved PEF.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Mometasone Furoate; Nitric Oxide; Pregnadienediols; Respiratory Function Tests; Salmeterol Xinafoate; Severity of Illness Index; Spirometry; Treatment Outcome

Consistent delivery of medication to treat asthma and chronic obstructive pulmonary disease (COPD) is critical for disease control. Dose tracking may eliminate the possibility of sub-therapeutic dosing. This study evaluated the overall performance, including accuracy and ruggedness, of the mometasone furoate/formoterol (MF/F) metered-dose inhaler (MDI) with an integrated numerical dose-counting mechanism in adolescent and adult subjects (aged ≥ 12 y) with persistent asthma or COPD.. In a phase III, open-label, single-arm, multicenter study, subjects demonstrating at least 90% compliance with MF/F during the screening period received twice daily MF/F MDI 100/10 μg with the integrated dose counter for 4 weeks. Accuracy and ruggedness of the dose counter were assessed by the overall discrepancy rate of subject-recorded actuations versus subject-recorded dose counter readings. Discrepancy rates for Counterstrip™, a manual counting method, were evaluated for reference. Compliance and ergonomic safety were also assessed.. The 233 subjects who used ≥ 90% of labeled actuations were included in the primary analysis. Of 26,317 total actuations, 33 dose counter discrepancies occurred (rate = 0.13/100 actuations), of which 13 were due to undercounting. In comparison, the Counterstrip discrepancy rate was 10-fold higher (1.34/100 actuations). Compliance with medication use, Counterstrip use, and e-diary recordings were all high (>98%). No new repetitive strain injuries or exacerbations of preexisting ergonomic injuries of the finger, hand, or arm were reported.. The MF/F MDI dose counter was accurate and rugged in subjects with asthma or COPD. No new repetitive strain injuries or exacerbations of existing ergonomic injuries were associated with inhaler use.. ClinicalTrials.gov identifier = NCT00604500.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Child; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Medication Adherence; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Pregnadienediols; Pulmonary Disease, Chronic Obstructive; Young Adult

The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone.. This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 μg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 μg. Men and women aged 15-85 years with chronic asthma, forced expiratory volume in 1 second (FEV(1)) 50-80% of the predicted value, and β-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV(1) over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting β-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count.. A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV(1), inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated.. Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV(1), symptoms, asthma control, and blood eosinophil count.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Chronic Disease; Confidence Intervals; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Linear Models; Male; Maximum Tolerated Dose; Middle Aged; Mometasone Furoate; Patient Compliance; Pregnadienediols; Quinolines; Reference Values; Risk Assessment; Severity of Illness Index; Spirometry; Sulfides; Treatment Outcome; United States; Young Adult

Inhaled delivery devices that are easy to use and facilitate dose tracking may lead to improved patient satisfaction and adherence. Patient satisfaction with a metered-dose inhaler (MDI) with an integrated dose counter containing a fixed-dose mometasone furoate/formoterol combination (MF/F MDI dose counter) was evaluated in subjects with persistent asthma or chronic obstructive pulmonary disease.. In this multicenter study (N = 272, age range: 12-92 years), subject experience and satisfaction with MDI devices was evaluated using baseline and poststudy surveys. Subjects responded to the baseline survey based on their previous MDI experience, then received MF/F MDI 100/10 μg with the integrated dose counter for 4 weeks before completing the poststudy survey. This evaluation was part of a broader study objective to assess performance of the MF/F MDI dose counter.. At baseline, 52% of subjects reported being extremely satisfied with their previous MDI. After using the MF/F MDI dose counter, a relative increase of 43% in overall satisfaction was observed. Approximately 90% of subjects agreed the MF/F dose counter helped them track doses and was easy to use; >80% agreed the inhaler was of good quality and well designed. Subjects agreed the dose counter relieved anxiety about running out of medication (68%) or taking a subtherapeutic dose (65%). Nearly 80% of subjects had no reservations about the MF/F MDI dose counter, and most subjects stated they would request it from their physician (66%) and recommend it to a friend (75%).. The MF/F MDI dose counter was found to be easy to use and have overall high patient satisfaction.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Child; Comprehension; Drug Combinations; Drug Therapy, Combination; Ergonomics; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Mometasone Furoate, Formoterol Fumarate Drug Combination; Patient Satisfaction; Pregnadienediols; Pulmonary Disease, Chronic Obstructive; Surveys and Questionnaires; Young Adult

To assess the effects of long-term mometasone furoate delivered via a dry powder inhaler (MF-DPI) on growth velocity and hypothalamic-pituitary-adrenal axis function in children with asthma.. Children aged 4-9 years with asthma (n = 187) were randomized to MF-DPI 100 μg (delivered dose; actuated dose is 110 μg) once daily in the morning (QD AM), 100 μg twice daily (BID), 200 μg QD AM, or placebo for 52 weeks followed by a 3-month follow-up period. The primary outcome was growth velocity calculated from stadiometric heights recorded at each visit. Secondary outcomes included serum and 12-h urinary cortisol, serum osteocalcin, and urinary N-telopeptide.. MF-DPI 100 μg QD AM treatment did not significantly affect growth velocity compared with placebo (-0.10 ± 0.31 cm/y, p = 0.76). When the effect of a total daily dose of 200 μg MF-DPI on growth velocity was examined, no significant effect was demonstrated for MF-DPI 100 μg BID compared with placebo (-0.64 ± 0.39 cm/y, p = 0.10), although the change in mean growth velocity with MF-DPI 200 μg QD AM reached statistical significance (-0.70 ± 0.29 cm/y, p = 0.02). The effects of all examined doses of MF-DPI on mean plasma cortisol levels were similar to cortisol changes seen in the placebo group, suggesting an absence of drug-related effects. No differences in 12-h urinary cortisol or other outcomes were observed between groups.. One year of treatment with a total daily dose of 100 μg of MF-DPI in the morning resulted in no significant difference, whereas a total daily dose of 200 μg of MF-DPI was associated with some changes in growth velocity when compared with placebo. The differences in growth velocity, and the absence of drug-related cortisol effects, support the use of a total daily dose of 100 μg of MF-DPI in children aged 4-9 years with mild persistent asthma.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Body Height; Child; Child, Preschool; Collagen Type I; Drug Administration Schedule; Female; Follow-Up Studies; Growth; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Least-Squares Analysis; Male; Mometasone Furoate; Osteocalcin; Peptides; Pituitary-Adrenal System; Pregnadienediols; Respiratory Function Tests

Inhaled corticosteroids can suppress the hypothalamic-pituitary-adrenal (HPA) axis with long-term exposure. This study reports the effects of moderate-dose (400 microg) mometasone furoate administered via dry powder inhaler (MF-DPI) once daily in the evening on the HPA axis in adults with mild to moderate asthma.. In this randomized, investigator-blind, placebo-controlled trial, nonsmoking adults aged 18 to 50 years with mild-to-moderate asthma received once-daily MF-DPI 400 microg (2 x 200 microg/inhalation; treatment A), MF-DPI 400 microg (1 x 400 microg/inhalation; treatment B), or placebo (two inhalations, treatment C), delivered at approximately 8:00 pm, for 42 days. Primary end points were area under the serum cortisol concentration-vs-time curve over 24 h (AUC(0-24)), 24-h urinary free cortisol (creatinine corrected) on day 42, maximum serum cortisol concentration (C(max)), time to C(max) (T(max)), and 8 :00 am serum cortisol concentration. This study was initiated April 16, 2001 and completed June 14, 2001.. Serum cortisol AUC(0-24), C(max), and 24-h urinary free cortisol levels decreased with all treatments by day 42 with no significant differences between groups. For treatment B, the change in 8:00 am serum cortisol from baseline to day 42 was significantly less than placebo (P = .04), attributed to a large baseline difference between these treatments. A significant difference in T(max) change from baseline by day 42 for treatment B compared with the other treatments (P = .019) was also attributed to significant baseline differences between groups. Actual values at day 42 for T(max) and 8:00 am serum cortisol were not significantly different between treatment groups (P > or = .275).. Once-evening moderate dosing (400 microg) MF-DPI does not suppress HPA axis function in adults with mild to moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Allergic Agents; Asthma; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Pituitary-Adrenal System; Pregnadienediols; Radioimmunoassay; Single-Blind Method; Treatment Outcome; Young Adult

Poor adherence with prescribed asthma medication is a major barrier to positive treatment outcomes. This study was designed to determine the effect of a once-daily administration of mometasone furoate administered via a dry powder inhaler (MF-DPI) on treatment adherence compared with a twice-daily administration.. This was a 12-week open-label study designed to mimic an actual clinical setting in patients >or=12 years old with mild-to-moderate persistent asthma. Patients were randomized to receive MF-DPI 400 microg once-daily in the evening or MF-DPI 200 microg twice-daily. Adherence was assessed primarily using the number of actual administered doses reported from the device counter divided by the number of scheduled doses. Self-reports were also used to determine adherence. Health-related quality of life, healthcare resource utilization, and days missed from work or school were also reported.. 1233 patients were randomized. The mean adherence rates, as measured by the automatic dose counter, were significantly better (P < 0.001) with MF-DPI 400 microg once-daily in the evening (93.3%) than with MF-DPI 200 microg twice-daily (89.5%). Mean adherence rates based on self-reports were also significantly better (P < 0.001) with MF-DPI 400 microg QD PM (97.2%) than with MF-DPI 200 microg twice-daily (95.3%). Adherence rates were lower in adolescents (12-17 years old). Health-related quality of life improved by 20% in patients using MF-DPI once-daily in the evening and by 14% in patients using MF-DPI twice-daily. Very few (<8%) patients missed work/school.. Mean adherence rates were greater with a once-daily dosing regimen of MF-DPI than with a twice-daily dosing regimen.This trial was completed prior to the ISMJE requirements for trial registration.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Child; Female; Humans; Male; Medication Adherence; Middle Aged; Mometasone Furoate; Powders; Pregnadienediols; Treatment Outcome; Young Adult

The combination of inhaled corticosteroid (ICS) and long-acting β₂-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS.. This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored.. The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC(0-24 h) observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2-6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.. One-year treatment with the new combination therapies - twice-daily MF/F-MDI 200/10 and 400/10 μg - is safe and well tolerated in patients with persistent asthma.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Cataract; Ethanolamines; Female; Formoterol Fumarate; Humans; Hydrocortisone; Intraocular Pressure; Male; Metered Dose Inhalers; Mometasone Furoate; Pregnadienediols; Single-Blind Method; Spirometry

Nocturnal symptoms are common in asthma patients and have the potential for considerable clinical effects due to a lack of sleep and persistent daytime symptoms of somnolence and activity impairment. The primary objective of this investigation was to determine the effect of a 14-day course of once-daily evening administration of mometasone furoate 400 microg administered via a dry powder inhaler (MF-DPI 400 microg qd pm) on the overnight decline in pulmonary function observed in patients with nocturnal asthma.. Eligible enrollees were between the ages of 18 and 60 years and had established mild to moderate asthma, with an improvement in forced expiratory volume in 1 second (FEV(1)) of >15% after administration of inhaled salbutamol (albuterol) 200 microg. All enrolled patients had a history of nocturnal asthma. Enrollees were randomized to receive MF-DPI 400 microg qd pm or placebo administered between 6 pm and 8 pm for 14 days. The primary outcome evaluated in the study was reduction in nocturnal decline in evening (8 pm) to morning (6 am) FEV(1) values. Secondary outcomes included reduction in nocturnal decline in evening to morning peak expiratory flow rate (PEFR), polysomnographic indices of sleep, and psychometric indices (Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire [NRQLQ], 36-item Short Form of the Medical Outcomes Survey [SF-36], and Asthma Quality of Life Questionnaire [AQLQ]).. A total of 20 patients were randomized and completed all phases of the study. No significant differences were observed between treatment groups in the primary outcome of nocturnal decline in FEV(1) from pretreatment to end of treatment. Likewise, there was no significant difference between treatment groups in polysomnographic indices of sleep or quality-of-life assessments. However, there was a trend toward improvement in the activity scale of the AQLQ assessment in the MF-DPI 400 microg qd pm treatment group.. No significant treatment effect on nocturnal pulmonary function, sleep indices or quality of life was observed with 14-day administration of MF-DPI 400 microg qd pm. These findings are limited by the small sample size and the short treatment period evaluated. Future studies are warranted to study the effects of MF-DPI therapy in patients with nocturnal asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Female; Humans; Lung; Male; Middle Aged; Mometasone Furoate; Pilot Projects; Polysomnography; Powders; Pregnadienediols; Respiratory Function Tests; Sleep; Young Adult

To assess the long-term pediatric safety of 2 doses of mometasone furoate administered via a dry powder inhaler (MF-DPI) for mild-to-moderate persistent asthma and compare them with that of beclomethasone dipropionate administered via a metered dose inhaler (BDP-MDI) in the treatment of persistent asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100 microg once-daily (QD) for children aged 4-11 years.. Children (N = 233) aged 4-11 years were randomized to 52 weeks of treatment with MF-DPI 200 microg QD AM, MF-DPI 100 microg twice daily (BID), or BDP-MDI 168 microg BID. Patients had used inhaled corticosteroids (ICSs) daily for > or = 30 days before the screening visit and were on stable ICS doses for > or = 2 weeks before screening. The primary safety variable was the incidence of adverse events. Secondary safety variables were laboratory tests (including cortisol concentrations), vital signs, and physical examination.. The incidence of adverse events was similar in all 3 treatment groups. The most frequently reported adverse event was upper respiratory tract infection, reported by 47%-49% of the MF-DPI-treated patients and 51% of the BPD-treated patients. Most adverse events were considered unrelated to study drug. The most frequently reported related adverse events were headache (MF-DPI 200 microg QD AM, 8%; MF-DPI 100 microg BID, 4%; BDP-MDI 168 microg BID, 2%) and oral candidiasis (4% in each treatment group). No clinically relevant changes in laboratory values, including plasma cortisol, vital signs, or physical examinations were noted in any treatment group.. Both MF-DPI doses were well tolerated, with no unusual or unexpected adverse events or safety concerns, and had a similar adverse event profile to that of BDP-MDI 168 microg BID.

Topics: Administration, Inhalation; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Humans; Hydrocortisone; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols

Exhaled nitric oxide (F(ENO)) and exhaled breath condensate (EBC) are noninvasive markers that directly measure airway inflammation and may potentially be useful in assessing asthma control and response to therapy.. To examine the time-dependent effects of inhaled corticosteroids on F(ENO) and EBC markers concomitantly with lung function and bronchial hyperresponsiveness.. Eleven steroid-naive adults with mild-to-moderate persistent asthma were treated with mometasone furoate dry powder inhaler, 400 microg/d, for 8 weeks, followed by a 4-week washout. Forced expiratory volume in 1 second (FEV1), the concentration of methacholine calculated to cause a 20% decline in FEV1 (PC20), F(ENO), EBC pH, and EBC nitrite measurements before, during, and after treatment were analyzed and compared.. The mean (SEM) FEV1 increased from 3.01 (0.13) L (82% predicted) to 3.24 (0.18) L (87% predicted) by week 8 (P < .05). The PC20 level increased from 1.28 (0.31) mg/mL to 2.99 (0.51) mg/mL by treatment week 8 (P < .05) and remained relatively stable through washout week 4 (P < .05). The F(ENO) level decreased from 31.1 (4.1) ppb to 20.6 (4.5) ppb by treatment week 1 (P < .01), remained low through treatment week 8 (P < .01), then trended back to the baseline level by washout week 1 (P < .01). The median EBC pH increased from 7.81 (interquartile range, 7.49-8.09) to 8.02 (interquartile range, 7.87-8.12) by treatment week 4, but did not achieve statistical significance. The EBC nitrite level decreased from 17.6 (1.6) microM to 9.3 (0.9) microM by treatment week 8 (P < .01), and remained low throughout washout week 4 (P < .05). There was a negative correlation between F(ENO) and PC20 (Spearman rank correlation coefficient = -0.50, P < .001).. The F(ENO) level responded the earliest to treatment and withdrawal of inhaled corticosteroids, whereas changes in EBC markers were delayed but more sustained.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Humans; Hydrogen-Ion Concentration; Inflammation; Lung; Male; Methacholine Chloride; Middle Aged; Mometasone Furoate; Nitrates; Nitric Oxide; Pregnadienediols; Young Adult

A total of 144 patients with lower airway symptoms suggestive of asthma, but who did not fulfil the functional criteria of asthma, were included in a randomised, double-blind, placebo-controlled 8-week "proof-of-concept" study with mometasone furoate (MF), 400 microg once daily. The primary efficacy variable was the mean change from baseline in six morning and evening weekly symptom scores: cough, sputum production, wheeze, shortness of breath, chest tightness and exercise-induced cough/wheeze. Total symptom scores were calculated after treatment for 4 and 8 weeks. Compared with placebo, MF improved total morning symptom score at 8 weeks. Changes in total evening symptom scores did not differ between treatments. MF improved all individual symptom scores more than placebo, although the differences in changes between treatments were not always statistically significant. Morning and evening peak expiratory flow rates increased with MF compared with placebo. MF reduced eosinophils and the levels of eosinophilic cationic protein in induced sputum. The results show that symptoms suggestive of asthma exist in patients without significant beta(2)-agonist reversibility or diurnal variability in peak flow. Once-daily MF may benefit some of these patients and a short course with inhaled corticosteroids may be tried. Responders should be better identified in further studies.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Double-Blind Method; Female; Humans; Lung; Male; Middle Aged; Mometasone Furoate; Placebos; Pregnadienediols; Steroids; Treatment Outcome

The control of daytime and nighttime symptoms is an important measure of effectiveness of asthma therapy, especially, when administered once-daily.. To evaluate the efficacy of evening and morning administrations of mometasone furoate administered via a dry powder inhaler (MF-DPI) 400 microg once-daily (QD) to show equivalence.. Open-label, randomized, parallel-group study in adult patients with mild to moderate asthma with a > or = 3-month history of ICS use. Patients received MF-DPI 400 microg QD either in the morning (AM) or evening (PM) for 12 weeks. The primary measure was the change in asthma symptoms from baseline to week 12. Secondary outcomes included response to treatment, adherence, inhaler device evaluation, use of rescue medication, urinary cortisol levels, and differential white blood cell count.. A total of 1537 patients were randomized; the efficacy population comprised 543 and 479 patients in the MF-DPI QD morning and evening groups, respectively. Mean improvements from baseline in daytime symptom scores at week 12 with morning and evening administration of MF-DPI 400 microg were -0.11+/-0.59 and -0.12+/-0.68, respectively (95% CI, -0.095 to 0.061) and the corresponding improvements in nighttime symptom scores were -0.08+/-0.59 and -0.07+/-0.50, respectively (95% CI, -0.067 to 0.068). Use of rescue medication was the same in both groups (1 puff/day). MF-DPI QD was well tolerated regardless of time of administration.. This open-label study did not identify differences between morning and evening dosing of MF-DPI 400 microg QD. A better effect of evening dosing compared to morning dosing found in previous double-blind placebo-controlled studies could not be confirmed.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Leukocyte Count; Lung; Male; Middle Aged; Mometasone Furoate; Peak Expiratory Flow Rate; Pregnadienediols; Treatment Outcome; Young Adult

The efficacy of the intranasal corticosteroid mometasone furoate nasal spray (MFNS) for treatment of nasal polyposis was demonstrated in 2 large clinical trials.. To evaluate the onset of MFNS symptomatic effect, data from the 2 trials were pooled and analyzed to determine the first day subjects experienced significant symptom relief.. Subjects with nasal polyposis randomized to MFNS 200 microg twice daily or placebo scored symptoms on a 3-point scale (0 = none; 3 = severe) and measured peak nasal inspiratory flow immediately before the morning dose. Onset of symptomatic effect was defined as the first day a statistically significant (P < .05) lasting response was observed for MFNS compared with placebo.. A total of 447 subjects with bilateral nasal polyps and clinically significant nasal congestion/obstruction were analyzed. Compared with placebo, MFNS 200 microg twice daily demonstrated statistically significant (P < .05) relief of anterior rhinorrhea by day 2 (-10.9% vs +5.7%), nasal congestion by day 3 (-15.1% vs -7.6%), postnasal drip by day 5 (+1.1% vs +4.6%), and sense of smell by day 13 (-9.6% vs -5.6%). Significant improvement in peak nasal inspiratory flow was seen by day 2 (increase of 6.22 L/min vs 1.48 L/min for placebo; P = .03).. Mometasone furoate nasal spray 200 microg twice daily rapidly improves the symptoms of nasal polyposis, leading to lasting relief of most major symptoms within 2 (24 hours after the first dose) to 5 days of initiating therapy.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Allergic Agents; Asthma; Double-Blind Method; Female; Humans; Inspiratory Capacity; Male; Middle Aged; Mometasone Furoate; Nasal Decongestants; Nasal Polyps; Pregnadienediols; Rhinitis, Allergic, Perennial; Smell

Rhinitis is common in asthmatic schoolchildren who are allergic to animal dander and constantly and indirectly exposed to these allergens in their everyday environment. As a patho-physiological linkage between nasal and bronchial inflammation has been proposed to exist, the primary objective of this study was to determine whether nasal administration of mometasone furoate (MSNF) can reduce bronchial inflammation, as reflected in the level of exhaled nitric oxide (F(E)NO) in asthmatic schoolchildren with dander allergy and mild-to-moderate rhinitis. Forty such children were assigned randomly to be treated for 4 wk with MSNF or placebo, employing a double-blind procedure. F(E)NO was the primary end-point measured and secondary end-points were nasal levels of NO, the concentration of eosinophilic cationic protein (ECP) in nasal lavage, the relative numbers of eosinophils in blood, forced expiratory volume in 1 s (FEV(1)), peak expiratory flow (PEF) and scoring of symptoms. There was no significant difference in the F(E)NO values of the treated and control groups at any time-point, whereas the nasal level of ECP was lower in the treated group compared with placebo (p = 0.05) on both days 7 and 28, and compared with baseline for the treated group (p = 0.06 on day 7, p = 0.02 on day 28). Furthermore, the mean blood eosinophil count decreased in the treated group, which also demonstrated lower scores for nasal symptoms compared with placebo, but neither of these differences were statistically significant. FEV(1), PEF and nasal levels of NO remained unchanged in both groups. Four weeks of nasal treatment with MSNF had no effect on bronchial inflammation, as reflected by exhaled NO, whereas signs of nasal and systemic eosinophil activation were reduced. Thus, nasal administration of a steroid as a strategy to reduce asthmatic inflammation remains questionable in mild-to-moderately severe cases of perennial rhinitis and asthma.

Topics: Adolescent; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Double-Blind Method; Eosinophil Cationic Protein; Eosinophils; Exhalation; Female; Humans; Leukocyte Count; Male; Mometasone Furoate; Nitric Oxide; Pregnadienediols; Pulmonary Ventilation; Rhinitis, Allergic, Perennial

Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity.. The efficacy and safety of mometasone furoate (MF) 400 microg twice daily (BID) and fluticasone propionate (FP) 500 microg BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). PM PEFR, forced expiratory volume in 1 second (FEV(1)), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed.. The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate.. MF-DPI 400 microg BID was therapeutically equivalent to FP-DPI 500 microg BID in patients with moderate-to-severe persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Peak Expiratory Flow Rate; Pregnadienediols; Treatment Outcome

The reduction of oral prednisone use by mometasone furoate (MF) delivered by HFA-227 metered dose inhaler (MDI) was examined in oral corticosteroid (OCS)-dependent patients with severe persistent asthma.. A 3-month, double-blind, placebo-controlled clinical trial (n=123), followed by a 9-month open-label phase (n=120). The study was conducted at 26 medical centers in the United States. Patients were randomized to treatment with MF-MDI 400 or 800 microg twice-daily (bid) doses, or placebo in the double-blind trial. All patients received MF in the open-label phase.. At the endpoint of the double-blind trial, MF-MDI 400 and 800 microg bid reduced the daily OCS dose by 39.4% and 31.1%, respectively, while placebo increased the OCS dose by 107.2% (P<0.01). The OCS requirement was reduced by 50% or more in 63% and 60% of patients treated with MF-MDI 400 and 800 microg bid, respectively, compared with 14% of patients receiving placebo. After 12 weeks, despite prednisone reductions, pulmonary function, asthma symptoms, albuterol use, nocturnal awakenings, and physician-evaluated response to therapy also showed significant improvement with MF-MDI treatment compared with placebo. Further reductions in OCS requirements were achieved with long-term MF-MDI treatment in the open-label phase, with an overall 67% reduction in prednisone usage and 51% of patients completely eliminating prednisone usage by the 1-year time point.. MF delivered by HFA-227 MDI significantly reduces daily OCS use compared with placebo and facilitates elimination of OCS use in patients with severe persistent asthma.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Prednisone; Pregnadienediols; Quality of Life; Treatment Outcome

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.. 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.. 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.. 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.. Mometasone furoate DPI (200 microg) administered once daily in the evening significantly improves pulmonary function in patients previously using SABAs alone for asthma control.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Mometasone Furoate; Peak Expiratory Flow Rate; Pregnadienediols

Mometasone furoate dry powder inhaler (DPI) has been shown to effectively treat asthma in children.. To evaluate the efficacy and safety of 2 dosing regimens of mometasone furoate DPI in the treatment of mild-to-moderate persistent asthma in children previously using inhaled corticosteroids (ICSs).. A 12-week, multicenter, double-blind, parallel-group, placebo-controlled study evaluated 2 dosing regimens of mometasone furoate DPI (100 microg every evening and 100 microg twice daily) in 296 children 4 to 11 years old with asthma previously using ICSs. The primary efficacy variable was the change in percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline to end point. Secondary efficacy variables included absolute FEV1, forced expiratory flow between 25% and 75% forced vital capacity, morning and evening peak expiratory flow, asthma symptom scores, albuterol use, nocturnal awakenings, response to therapy, and health-related quality of life.. Mean changes from baseline at end point in predicted FEV1 were 4.73 and 5.52 percentage points for mometasone furoate DPI, 100 microg every evening and 100 microg twice daily, respectively, the difference of which was not significant, and -1.77 percentage points for placebo (P < or = .002). Significant improvements in secondary efficacy variables were also observed for both mometasone furoate DPI treatments over placebo. Both mometasone furoate DPI doses were well tolerated, and no significant differences were noted among the 3 treatment groups in adverse event reporting.. Both mometasone furoate DPI doses were well tolerated and significantly improved lung function, maintained effective asthma control, and improved quality of life in children with asthma.

Topics: Abdominal Pain; Administration, Inhalation; Anti-Allergic Agents; Asthma; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Headache; Humans; Male; Mometasone Furoate; Powders; Pregnadienediols; Quality of Life; Respiratory Function Tests; Spirometry; Treatment Outcome

Mometasone furoate dry powder inhaler (MF-DPI) [400 mug] is an inhaled corticosteroid (ICS) that is effective in the treatment of asthma. MF-DPI has a low potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis at its clinical dose. The effect of MF-DPI, 400 microg qd, on the HPA axis was compared to that of beclomethasone dipropionate (BDP) using hydrofluoroalkane (HFA) and chlorofluorocarbon (CFC) propellants via metered-dose inhalers (MDIs) twice daily.. This randomized, third-party blind, parallel-group study compared the effects of MF-DPI 400 mug one puff qd in the morning (n = 18), HFA-BDP 200 microg two puffs MDI bid (n = 18), and CFC-BDP 400 microg two puffs MDI bid (n = 17) for 14 days on the area under the 24-h serum cortisol concentrations curve (AUC(0-24)) and on total 24-h urinary free cortisol excretion in mild asthmatic subjects. Effects on morning/evening peak expiratory flow (PEF) and on inhaled albuterol use were also assessed. Adverse events that occurred during or > or = 30 days after the study were recorded.. The mean decrease from baseline in the serum cortisol concentrations AUC(0-24) in the MF-DPI group was significantly less than in either the HFA-BDP (p = 0.024) or the CFC-BDP (p = 0.011) groups. Decreases in serum cortisol concentrations AUC(0-24) in the two BDP groups did not differ from one another. The MF-DPI group trended toward higher morning and evening PEF than either BDP group. Treatment-associated adverse events were reported by seven subjects in the MF-DPI group, vs one subject in the HFA-BDP and three subjects in the CFC-BDP groups; these were mild, and no subject discontinued treatment due to an adverse event.. Fourteen days of treatment with MF-DPI 400 microg qd was associated with a significantly lesser decrease in the serum cortisol concentrations AUC(0-24) compared with HFA-BDP 200 microg MDI or CFC-BDP 400 microg MDI bid.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Beclomethasone; Chlorofluorocarbons; Creatinine; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant, Newborn; Male; Middle Aged; Mometasone Furoate; Pituitary-Adrenal System; Pregnadienediols

Once-daily dosing with an inhaled corticosteroid (ICS) may simplify asthma management and improve patient compliance. Since asthma is frequently worse at night, evening dosing appears to be a more obvious choice to accommodate the chronobiology of asthma than morning dosing.. The primary study objective was to compare the efficacy and safety of mometasone furoate (MF) dry powder inhaler (MF-DPI) 400 microg qd PM (one 400 microg inhalation) with placebo for the treatment of asthma in patients previously dependent on twice a day (bid, bis in die) ICS therapy. We also compared different regimens of MF-DPI with each other and with placebo.. This 12-week, multicenter, double-blind, placebo-controlled study evaluated lung function and asthma symptoms in 400 subjects with persistent asthma randomized to MF-DPI 200 microg qd (once a day, quaque die) PM, 400 microg qd PM as one inhalation from a 400 microg device, 400 microg qd PM as two inhalations from a 200 microg device, 200 microg twice daily (bid), or placebo. Evening doses were to be taken in the late afternoon or early evening, preferably before dinner time.. Mean changes from baseline at endpoint in FEV1 (forced expiratory volume in 1 s) were similar for MF-DPI 400 microg qd PM (one inhalation; 0.41 L), MF-DPI 400 microg qd PM (2 inhalations; 0.49 L), MF-DPI 200 microg qd PM (0.41 L), and MF-DPI 200 microg bid (0.51 L); and all were significantly improved compared with placebo (0.16 L; p < 0.001). Secondary efficacy variables, including nocturnal awakenings and use of rescue albuterol, were also significantly improved with MF-DPI treatment compared with placebo. All treatments were generally safe and well tolerated, with adverse events of mild to moderate severity.. Once-daily evening dosing of MF-DPI at doses of 400 and 200 microg restored lung function and improved nocturnal and daytime symptom control in subjects with asthma previously dependent on bid ICS therapy. Comparable effectiveness of a total daily dose of 400 microg was demonstrated between once daily in the evening and twice-daily administration. The results also confirm the effectiveness of MF-DPI 200 microg qd PM, the lowest dose studied.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Asthma; Chronic Disease; Disease Progression; Female; Humans; Male; Middle Aged; Mometasone Furoate; Patient Compliance; Pregnadienediols; Quality of Life; Surveys and Questionnaires; Treatment Outcome

The chronobiology of asthma suggests that, for once-daily dosing, an evening dose may be the most effective treatment paradigm.. To evaluate the efficacy and safety of mometasone furoate dry powder inhaler (MF-DPI) administered once daily in the evening or twice daily in patients with asthma previously maintained on twice-daily regimens of inhaled corticosteroids.. In this 12-week, multicenter, placebo-controlled trial, 268 subjects > or =12 years of age with inhaled corticosteroid-dependent asthma and baseline forced expiratory volume in 1 second (FEV(1)) between 50% and 85% of predicted were randomized to receive treatment with MF-DPI 400 mug once daily in the evening, MF-DPI 200 mug twice daily, or placebo. The primary efficacy variable was mean change in FEV(1) from baseline to endpoint. Other lung function measures, asthma symptoms, quality of life, and rescue medication use also were assessed.. At endpoint, mean FEV(1) was significantly improved with both MF-DPI doses compared with placebo (p < 0.001). The 2 active treatment groups were statistically indistinguishable from each other. Secondary efficacy variables, including nocturnal awakenings, asthma worsenings, quality of life, and rescue medication use, were also significantly improved for both MF-DPI treatments compared with placebo. Both dosages were well tolerated; no clinically meaningful changes in laboratory values or vital signs were observed.. MF-DPI 400 mug once daily in the evening was as effective as MF-DPI 200 mug twice daily in improving pulmonary function, asthma symptoms, and quality of life compared with placebo in subjects previously using twice-daily regimens of an inhaled corticosteroid.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Female; Humans; Lung; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Respiratory Function Tests

Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 microg/day) or MF Twisthaler (400, 800, and 1,600 microg/day). For the 21 per protocol completed patients, there was significant suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs-as geometric mean fold suppression (95% confidence interval) from baseline: FP 2,000 microg, 1.85 (1.21-2.82, p = 0.002); FP 1,000 microg, 1.45 (1.07-1.96, p = 0.02); MF 1,600 microg, 1.92 (1.26-2.93, p = 0.001); and MF 800 microg, 1.39 (1.04-1.88, p = 0.02). For secondary outcomes of 8:00 A.M. plasma cortisol, serum osteocalcin, and early morning urinary cortisol/creatinine, there was significant suppression with MF and FP at the highest dose. Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adult; Aged; Androstadienes; Asthma; Biological Availability; Confidence Intervals; Creatinine; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Mometasone Furoate; Multivariate Analysis; Pregnadienediols; Probability; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome; Urinalysis

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Androstadienes; Asthma; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pregnadienediols

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 microg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI-treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI-treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p<0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.

Topics: Administration, Inhalation; Administration, Oral; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Female; Humans; Male; Middle Aged; Mometasone Furoate; Powders; Pregnadienediols; Quality of Life; Sickness Impact Profile; Treatment Outcome

We conducted this study to compare the efficacy and safety of once-daily mometasone furoate (MF) administered by dry powder inhaler (DPI) with once-daily budesonide (BUD)-DPI and placebo in patients with moderate persistent asthma previously using twice-daily inhaled corticosteroids. A total of 262 patients (> or = 12 years of age) with moderate persistent asthma were randomised to once-daily morning treatment with MF-DPI 440 microg (metered dose), BUD-DPI 400 microg (metered dose), or placebo in an eight-week, multicentre, placebo-controlled, double-blind, double-dummy study. The primary efficacy variable was percent change in FEV1 from baseline to endpoint (last evaluable visit). At endpoint, the percent change in FEV1 was significantly greater (p < 0.01) following treatment with MF-DPI 440 microg (8.9%) than with both BUD-DPI 400 microg (2.1%) and placebo (-3.9%). Secondary efficacy variables, including morning and evening peak expiratory flow rates, albuterol use, percentage of asthma symptom-free days, and physician-evaluated response to therapy were also significantly improved at endpoint in the MF-DPI group compared with both the placebo and BUD-DPI groups (p < 0.05). Both active treatments were well tolerated. In conclusion, once-daily treatment in the morning with MF-DPI 440 microg significantly improved pulmonary function and asthma control compared with morning administration of BUD-DPI 400 microg and placebo.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Forced Expiratory Volume; Humans; Middle Aged; Mometasone Furoate; Pregnadienediols; Respiratory Function Tests; Treatment Outcome

The rapid growth of clinical trials sponsored by the pharmaceutical industry and conducted by community physicians raises concerns about the scientific quality of this research and the adequacy of protections for research participants. In this article, we present an in-depth ethical analysis of a recent industry-sponsored placebo-controlled study for treatment of asthma. The ethical analysis uses a proposed ethical framework for evaluating clinical research focusing on seven ethical requirements: (1) scientific value, (2) scientific validity, (3) fair subject selection, (4) favorable risk/benefit ratio, (5) independent review, (6) informed consent, and (7) respect for enrolled subjects.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Conflict of Interest; Controlled Clinical Trials as Topic; Double-Blind Method; Drug Industry; Ethics Committees, Research; Ethics, Medical; Female; Forced Expiratory Volume; Humans; Informed Consent; Male; Mometasone Furoate; Patient Selection; Pregnadienediols; Research Support as Topic; Treatment Outcome

Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first-choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms.. One hundred and one patients (M/F = 62/39, age range 12-62 years) with pollen-induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n = 30) with drug therapy alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season.. The rate of noncompliance/dropout was highest in the untrained patients (P = 0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P = 0.02).. Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs.

Topics: Administration, Intranasal; Adolescent; Adult; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Child; Disease Management; Female; Humans; Male; Middle Aged; Mometasone Furoate; Patient Compliance; Patient Dropouts; Patient Education as Topic; Pregnadienediols; Rhinitis, Allergic, Seasonal

Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma.. 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.. 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.. 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.. 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.

Topics: Administration, Intranasal; Adult; Anti-Inflammatory Agents; Asthma; Circadian Rhythm; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Mometasone Furoate; Powders; Pregnadienediols; Respiratory Function Tests; Therapeutic Equivalency

Mometasone furoate (MF) is a new inhaled glucocorticoid administered by dry powder inhaler (DPI).. MF-DPI was evaluated for safety and efficacy and compared with placebo DPI and beclomethasone dipropionate (BDP) administered by metered dose inhaler (MDI) in the treatment of patients with moderate persistent asthma.. Eligible patients (n = 227), 13 to 75 years of age, maintained on inhaled glucocorticoids before entering the trial, were randomized to receive: MF-DPI, 100 microg, twice daily, MF-DPI, 200 microg, twice daily, BDP MDI, 168 microg, twice daily, or placebo in a 12-week, multicenter, double-blind study.. At endpoint, FEV1 (primary efficacy variable) significantly improved for all three active treatments compared with placebo (P < .01, all comparisons). The response to MF-DPI, 200 microg, twice daily treatment was approximately twice as large as the response to MF-DPI, 100 microg, twice daily or BDP MDI treatment, although the differences between these groups did not reach statistical significance. Secondary efficacy variables including PEFR, asthma symptoms, nocturnal awakenings, and albuterol use showed similar trends. The MF-DPI, 100 microg, twice daily and BDP MDI, 168 microg, twice daily treatment groups produced comparable results for all efficacy variables.. MF-DPI, 100 microg and 200 microg, twice daily were well-tolerated and significantly improved lung function and symptom control in the treatment of patients with moderate persistent asthma. In this study, MF-DPI, 200 microg, twice daily seemed to be the most effective dosage.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Mometasone Furoate; Peak Expiratory Flow Rate; Powders; Pregnadienediols; Therapeutic Equivalency

Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability.. 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.. A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial.. Sixty centers in 20 countries.. Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment.. 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).. 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.. 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.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols; Pulmonary Ventilation; Sleep Initiation and Maintenance Disorders

Comparisons of the potency of different inhaled corticosteroids, delivery devices, and treatment regimens in the management of asthma can only be made when outcome measurements display a dose-dependent effect. These outcomes have been difficult to identify. In this study, we compared in a randomized, double-blind, crossover design, the effects of 6 d treatment with placebo and three doses (50, 100, and 400 microg, twice daily) of mometasone furoate delivered by dry powder inhaler (MF-DPI) on responses after allergen inhalation challenge. Twelve mild asthmatic subjects with dual responses after allergen inhalation were studied. Outcome measurements included early and late asthmatic responses, the change in methacholine airway responsiveness 24 h after challenge, and sputum eosinophilia measured 7 and 24 h after challenge. All three doses of MF-DPI demonstrated similar attenuation of early responses and allergen-induced airway hyperresponsiveness relative to placebo (p < 0.05). The late maximal %fall in FEV(1) after placebo treatment was 23.5% and was significantly reduced in a dose-dependent manner to 12.3%, 11.0%, and 5.9% for the 50-, 100-, and 400-microg twice-daily treatments (p = 0.007). The allergen-induced increase in sputum eosinophilia (x10(4) cells/ml) 24 h after challenge during placebo treatment was 60.2 and was significantly reduced to 24.0, 15.3, and 6.2 for the 50-, 100-, and 400-microg twice-daily treatments. MF-DPI is effective at attenuating allergen-induced early and late responses, airway hyperresponsiveness, and sputum eosinophilia, and dose-response effects exist for the attenuation of the late response.

Topics: Administration, Inhalation; Adolescent; Adult; Airway Resistance; Allergens; Anti-Inflammatory Agents; Asthma; Bronchoconstrictor Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Inflammation; Male; Methacholine Chloride; Middle Aged; Mometasone Furoate; Pregnadienediols; Severity of Illness Index; Sputum; Time Factors; Treatment Outcome

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.. 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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Quality of Life; Respiratory Function Tests; Treatment Outcome

Mometasone furoate (MF) is a new potent corticosteroid for use in treating asthma.. 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.. 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.. 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.. Treatment with low doses of MF DPI decreased airway responsiveness to AMP challenge and improved secondary measures of pulmonary function and asthma symptoms.

Topics: Adenosine Monophosphate; Administration, Inhalation; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchoconstriction; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Forced Expiratory Volume; Humans; Mometasone Furoate; Peak Expiratory Flow Rate; Pregnadienediols

Despite current recommendations, many patients with persistent asthma are still treated with bronchodilators alone.. The safety and efficacy of two once daily dosing regimens (200 microg and 400 microg) of mometasone furoate (MF) administered in the morning by using a dry-powder inhaler (DPI) were compared with those of a twice daily dosing regimen (200 microg administered twice daily) in patients with mild-to-moderate persistent asthma previously taking only inhaled beta(2)-adrenergic agonists.. All patients (306 patients; age range, 12-70 years) were given a diagnosis of asthma for at least 6 months before enrollment in this 12-week, placebo-controlled, double-blind, randomized study. The primary efficacy variable was change in FEV(1) from baseline to endpoint (last evaluable visit).. At endpoint, FEV(1) was significantly improved (P < or =.02) after MF-DPI 400 microg once daily morning treatment and MF-DPI 200 microg twice daily treatment (16.0% and 16.1%, respectively) compared with placebo (5.5%). The improvement seen with MF-DPI 200 microg once daily morning treatment (10.4%) was not significantly different from that with placebo. Secondary efficacy variables also showed significant improvement for the MF-DPI 400 microg once daily morning treatment group and the MF-DPI 200 microg twice daily treatment group compared with the placebo group. All doses of MF administered by means of a DPI were well tolerated.. This is the first study to demonstrate that a total daily dose of 400 microg of MF administered by means of a DPI is an effective treatment for patients with mild-to-moderate persistent asthma previously taking only inhaled beta(2)-adrenergic agonists. This treatment was equally effective when administered either as a once daily or twice daily regimen.

Topics: Adolescent; Adult; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Circadian Rhythm; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Respiratory Function Tests

Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control.. 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.. 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.. 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.. MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Consumer Product Safety; Double-Blind Method; Female; Glucocorticoids; Health Status; Humans; Male; Middle Aged; Mometasone Furoate; Prednisone; Pregnadienediols; Quality of Life; Respiratory Function Tests

To investigate the potential for mometasone furoate (MF) to exert systemic effects following administration by dry powder inhaler (DPI) or metered-dose inhaler (MDI).. Three randomized, evaluator-blind, placebo-controlled, parallel-group, 28-day studies.. Adults with mild-to-moderate persistent asthma.. Study 1 (12 patients per treatment group; MF DPI at 200 microg bid, 400 microg qd, 800 microg qd, or 1,200 microg qd). Study 2 (16 patients per treatment group; MF DPI at 400 microg bid or 800 microg bid, or oral prednisone at 10 mg qd). Study 3 (16 patients per treatment group; MF MDI at 400 microg bid or 800 microg bid, or fluticasone propionate [FP] at 880 microg bid by MDI).. Study 1. Plasma concentrations were near the lower limit of quantitation (50 pg/mL) at the MF DPI 400-microg qd dosage and approximately 250 pg/mL at the 1,200-microg qd dosage. The area under the curve for serum cortisol concentrations over 24 h (AUC(24)) was essentially unaltered at all doses. Study 2. Plasma levels over days 7 to 28 were 100.3 +/- 5.9 pg/mL (mean +/- SEM) for MF DPI 400 microg bid, and 181.0 +/- 10.9 pg/mL for 800 microg bid. Although there were relatively low levels of suppression (19 to 25%) at earlier time points for MF DPI 400 microg bid, serum cortisol AUC(24) levels at day 28 were similar to placebo. MF DPI 800 microg bid and oral prednisone both decreased serum cortisol AUC(24) levels at days 7 to 28 by 28.0 +/- 8.3% and 67.2 +/- 3.6%, respectively. The response to cosyntropin was normal in 15, 14, 11, and 1 of the patients in the placebo, MF DPI 400 microg bid, MF DPI 800 microg bid, and prednisone groups, respectively. Study 3. MF MDI caused even less systemic exposure than by DPI. MF MDI 800 microg bid (24.0 +/- 3.1%) and FP (51.7 +/- 3.8%) caused a significant decrease in serum cortisol AUC(24) on days 14 to 28. MF MDI 400 microg bid was similar to placebo treatment at all time points.. The MF 800-microg bid dosage (1,600 microg/d), which is twice the highest projected clinical dosage, represents the lower limit for consistently detectable systemic effects of MF.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Mometasone Furoate; Pituitary-Adrenal System; Prednisone; Pregnadienediols

Mometasone furoate (MF) administered by dry powder inhaler (DPI) was composed with budesonide (BUD) Turbuhaler in the treatment of moderate persistent asthma. The patients were randomized to one of four treatment groups: MF DPI (100, 200, 400 microg b.i.d) or BUD Turbuhaler. 400 microg b.i.d in a 12-week, active-controlled, evaluator-blind, multicentre international trial. The primary efficacy variable was the mean change from baseline to endpoint (last treatment visit) in forced expiratory volume in one second (FEV1). Changes in FEV1 showed a statistically significant superiority (p<0.05) of MF DPI 200 and 400 microg b.i.d compared with the BUD Turbuhaler 400 microg b.i.d treatment. Significant superiority (p<0.05) was also seen in scores for several secondary efficacy variables when MF DPI was compared with BUD Turbuhaler treatment. MF DPI 200 microg b.i.d was comparable to MF DPI 400 microg b.i.d in therapeutic benefit. The incidence of oral candidiasis was no more than 3% in any group. All treatments were well tolerated. A total daily dose of 400 microg of mometasone furoate administered by dry powder inhaler provides a well-tolerated treatment for patients with moderate persistent asthma and results in a significantly greater improvement, when compared to a daily dose of 800 microg BUD Turbuhaler in the parameters measured in this study.

Topics: Adolescent; Adult; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Circadian Rhythm; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols; Safety; Single-Blind Method; Sleep; Time Factors

A new inhaled suspension formulation of mometasone furoate (MF), a potent corticosteroid with minimal systemic availability, has been developed for the treatment of asthma. This formulation is delivered by metered-dose inhaler (MDI) using the nonchlorofluorocarbon propellant hydrofluoroalkane 227 (HFA-227).. The primary goal of this study was to determine the respiratory tract deposition of this formulation of MF. A secondary objective was to measure plasma concentrations of MF and a putative metabolite, 6-X-OH MF, to determine the systemic exposure to corticosteroid.. This was a single-dose, open-label study in which 200 microg of technetium 99m (99mTc)-radiolabeled MF was administered to patients with asthma. Gamma scintigraphy was used to quantify lung, oropharyngeal, stomach, and MDI mouthpiece deposition patterns of MF.. Eleven patients, aged 21 to 47 years, with a history of asthma were enrolled in and completed the study. The mean (+/- SD) whole lung deposition of MF was 13.9%+/-5.7% of the metered (ex-valve) dose. The central lung zone received 5.3%+/-2.8% of the dose; the intermediate zone received 4.7%+/-1.9%; and peripheral lung deposition was 4.0%+/-1.5%. The mean (+/- SD) ratio of peripheral to central lung deposition was 0.8+/-0.2. Oropharyngeal deposition was 79.1%+/-8.7% of the ex-valve dose, with 6.3%+/-7.8% deposited on the MDI mouthpiece and 0.7%+/-0.5% exhaled. The majority of plasma samples taken for analysis of MF and 6-13-OH MF concentrations were below the limit of quantification (50 pg/mL) in all patients after inhalation of 200 microg 99mTc-labeled ME CONCLUSION: The lung deposition of MF when administered via HFA-227 MDI is comparable to the 10 to 20% lung deposition seen with other corticosteroid suspension for- mulations administered by MDI that have demonstrated effectiveness in the treatment of asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; History, 16th Century; Humans; Lung; Middle Aged; Mometasone Furoate; Organotechnetium Compounds; Pregnadienediols; Radionuclide Imaging

A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Middle Aged; Mometasone Furoate; Peak Expiratory Flow Rate; Pregnadienediols; Treatment Outcome; Vital Capacity

We reviewed recent clinical studies evaluating the safety and efficacy of LABA/LAMA/ICS fixed dose combinations by searching the PubMed database. Molecular mechanisms and clinical data support the use of a once-daily, single-inhaler fixed dose combination of the LABA/LAMA/ICS indacaterol/glycopyrronium/mometasone (IND/GLY/MF), the first therapy combining three agents in a fixed dose approved in Europe for the treatment of uncontrolled asthma.. IND/GLY/MF was superior to both IND/MF and salmeterol/fluticasone, a well-established LABA/ICS combination improving the lung function in uncontrolled asthma. Moreover, IND/GLY/MF, delivered through the Breezhaler inhaler in a single inhalation, is the first inhaled therapy prescribed alongside a digital companion, a sensor and the Propeller app, allowing for improved treatment adherence, reduced rescue inhaler usage and hospitalizations, increased patient satisfaction and asthma control.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Muscarinic Antagonists; Quinolones

A very limited option of inhaled corticosteroids (ICSs) is approved for pediatric use in China because in children the use of ICSs for long periods is associated with dose-dependent growth reduction. Due to the lack of consensus on which is the best ICS-based treatment option to manage mild persistent asthma in children, the present study was performed to evaluate the efficacy and safety of budesonide (BUD)-based therapy vis-à-vis mometasone-based therapy in children with mild persistent asthma.. A single-center, retrospective study was conducted in asthmatic children aged between 6 and 11 years. BUD and mometasone furoate (MF) were administered as per the approved dosing regimen using pressurized metered-dose inhalers via oral inhalation route for a period of 12 weeks. The study outcome was assessed in terms of the forced expiratory volume in 1 s (FEV1), symptom scores, and nonoccurrence of side effects.. Among the 77 asthmatic children, 71 completed the study treatment and were used in carrying out the analysis. The improvement of spirometric parameters like FEV1, Tiffeneau-Pinelli index (FEV1/forced vital capacity [FVC]), and peak expiratory flow (PEF) values observed in the MF cohort was significantly greater than those of the BUD cohort (p < 0.05 for all). An increase of approximately 12%/child was observed for FEV1/FVC ratios for the BUD cohort and MF cohorts. After the 12-week study, the PEFm and PEFe values increased to about 50 L/min/child for the BUD cohort and about 98 L/min/child for the MF cohort. During the study, no asthma exacerbation event was observed in the MF cohort, whereas 1 child in the BUD cohort had asthma exacerbation in week 4. The use of rescue medication during the study was required for 16.2 and 6% of children, respectively, for BUD and MF cohorts. Owing to low dosing frequency, MF could provide a better treatment approach than BUD due to improved patient compliance.. Although both drugs showed improvement in the quality of life of asthmatic children with manageable treatment-emergent adverse effects, the improvement was augmented in MF-treated children.. The level of evidence was III. Technical Efficacy Stage: The technical efficacy stage was 4.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Child; China; Drug Dosage Calculations; Female; Humans; Male; Metered Dose Inhalers; Mometasone Furoate; Quality of Life; Respiratory Function Tests; Retrospective Studies

Here we present pharmacological and clinical properties of a new fixed triple inhaled combination including an inhaled corticoid, a long acting ?2 agonist and a long acting anticholinergic for the treatment of severe asthma. Enerzair® is the name of this triple combination which contains 160 µg mometasone, 150 µg indacaterol and 50 µg glycopyrronium administered by a Breezhaler®. As compared to an ICS/LABA combination Enerzair® improves expiratory flow rates and reduces exacerbation rate. The Breezhaler® device may be coupled to a sensor (Propeller Health) that, through a bluetooth system, allows to control patient adherence and provides recall to the patient to take his aerosol.. Nous présentons, dans cet article, les propriétés pharmacologiques et les effets cliniques d’une nouvelle triple combinaison fixe inhalée comprenant un corticoïde inhalé, un ?2 mimétique à longue durée d’action et un anticholinergique à longue durée d’action destinée au traitement de l’asthme sévère. Cette combinaison qui porte le nom d’Enerzair® regroupe dans le même dispositif (le Breezhaler®) 160 µg de mométasone, 150 µg d’indacatérol et 50 µg de glycopyrronium. Par rapport à une combinaison corticoïde inhalé et ?2 mimétique, l’Enerzair® améliore la valeur des débits expiratoires et réduit la fréquence des exacerbations. Le dispositif peut être couplé à un capteur (Propeller Health) qui, par un système bluetooth, offre la possibilité de surveiller l’adhérence au traitement et fournit un rappel de prise au patient.

Topics: Administration, Inhalation; Asthma; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Pulmonary Disease, Chronic Obstructive; Quinolones

In asthma, symptom control is a primary goal that is not consistently met with available treatment options. The first commercially available fixed-dose combination in a single inhaler of a long-acting beta-agonist (indacaterol, IND), an inhaled corticosteroid (mometasone furoate, MF) and a long-acting muscarinic antagonist (glycopyrronium, GLY) has shown promising clinical results in phase III trials. The aim of the present study is to evaluate the cost-utility of IND/GLY/MF fixed-dose combination relative to a combination of salmeterol/fluticasone and tiotropium or salmeterol/fluticasone or IND/MF in adult patients with asthma, from the Italian Health Service (NHS) perspective.. A two-state and 4-week cycle Markov model was used to estimate lifetime clinical outcomes and costs. Patients entered the model in stable disease and could experience a non-fatal exacerbation event. The exacerbation rate is dependent upon the therapy a patient is receiving, as per the IND/GLY/MF clinical trials. The impact of each type of exacerbation is accounted by applying a utility decrement, obtained from the literature, and a treatment cost. Utility values were obtained from the EQ-5D questionnaires in the IND/GLY/MF clinical trials. Lifetime costs considered in the analysis were drugs and exacerbation management. Probabilistic sensitivity analyses were carried out, with the aim of evaluating the impact of uncertainty on input parameters.. IND/GLY/MF is associated with a higher quality of life [+ 0.25 quality-adjusted life-year (QALY)] than salmeterol/fluticasone plus tiotropium, with an incremental cost of -€3213.90. The incremental cost-utility ratio indicates dominance. At a threshold of €5000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.21 QALY) than salmeterol/fluticasone, with an incremental cost of €2547.76. Incremental cost-utility ratio results in €11,897 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective. IND/GLY/MF is associated with a higher quality of life (+ 0.34 QALY) than IND/MF, with an incremental cost of €4745.91. Incremental cost-utility ratio results in €14,088 per QALY. At a threshold of €20,000 per QALY, IND/GLY/MF has nearly a 100% probability of being cost effective.. The results indicate that IND/GLY/MF is cost effective against the considered comparators in a cohort representative of adult patients with asthma in Italy.

Topics: Acetates; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Drug Combinations; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Treatment Outcome

This was a randomized, double-blind, double-dummy, four-week, parallel-group study of 739 adolescents and adults with persistent asthma. Eligible patients were receiving ICS treatment up to the maximum dose per day on a stable regimen for at least four weeks before screening. The study population was enriched for patients who were responsive to ICS therapy. The primary objective of the present study was to show non-inferiority of these doses, i.e. the low (80 μg) and high (320 μg) doses of MF delivered via Breezhaler® once daily, compared with the corresponding low (200 μg) and high (800 μg) doses of MF delivered via Twisthaler® once daily. The primary endpoint was 24 h post-dose trough forced expiratory volume in 1 s (FEV. The LS mean difference in trough FEV. The similarities in effects on lung function and ACQ after four weeks of treatment demonstrate the comparability of MF at low (80 μg) and high (320 μg) doses delivered with Breezhaler® with MF at low (200 μg) and high (800 μg) doses delivered with Twisthaler®, respectively. The study formally demonstrated that MF, delivered via Breezhaler®, is non-inferior to MF, delivered via Twisthaler® at corresponding ICS doses.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Drug Combinations; Female; Humans; Lung; Male; Middle Aged; Mometasone Furoate; Random Allocation; Treatment Outcome; Young Adult

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Drug Administration Schedule; Drug Combinations; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Indans; Mometasone Furoate; Quinolones

Topics: Asthma; Eosinophils; Humans; Mometasone Furoate; Sputum; Tiotropium Bromide

Topics: Administration, Inhalation; Aged; Anti-Asthmatic Agents; Asthma; Drug Substitution; Female; Humans; Mometasone Furoate; Ocular Hypertension

Indirect comparison (IC) and direct comparison (DC) of four inhaled corticosteroid (CS) treatments for asthma were conducted, and the factors that may influence the results of IC were investigated. Among those factors, we focused on the effect of common comparator selection in the treatment of asthma, where little control group bias or placebo effect is expected.. IC and DC were conducted using the change from baseline in forced expiratory volume in 1 s (FEV1(L)) as an outcome parameter. Differences between inhaled CS were evaluated to compare the results of IC and DC. As a common comparator for IC, placebo (PLB) or mometasone (MOM) was selected. Whether the results of IC are affected by the selection of a common comparator and whether the results of IC and DC are consistent were examined.. 23 articles were identified by a literature search. Our results showed that ICs yielded results similar to DCs in the change from baseline of FEV1(L). No statistically significant difference was observed in inconsistency analysis between ICs and DCs. It was clinically and statistically confirmed that ICs with PLB and those with MOM did not differ in terms of the results of FEV1(L) analysis in this dataset.. This study demonstrated that ICs among inhaled CS can deliver results consistent with those of DCs when using the change from baseline in FEV1(L) as an outcome parameter in asthma patients. It was also shown that using an active comparator has similar results if there is no effect of control group bias. It should be emphasized that the investigation of control group bias is a key factor in conducting relevant ICs so that an appropriate common comparator can be selected.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Databases as Topic; Forced Expiratory Volume; Humans; Mometasone Furoate; Placebos; Treatment Outcome

After the SMART trial evaluating the safety of salmeterol (long-acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken to promote a guideline-adherent prescribing of LABA only to patients receiving inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related prescription patterns after the SMART trial in Germany.. Patients documented in the Bavarian Association of Statutory Health Insurance Physicians database (approximately 10.5 million people) were included if they had a diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004 and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane Armitage tests were used for time trend analyses.. Highest annual PPRs were found for budesonide and the fixed combination of salmeterol/fluticasone. The proportion of "concomitant LABA and ICS users" increased from 52.0 to 57.6% within the study period, whereas for "LABA users without ICS" a slight decrease from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one quarter with a LABA prescription without concomitant ICS was highest in elderly, male patients (≈20%). In the majority of these patients, a concomitant diagnosis of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present.. Between 2004 and 2008, we found a moderate increase in guideline-adherent LABA prescribing in a representative German population. Elderly men received a significant number of LABA prescriptions without concomitant ICS probably due to ACOS.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Beclomethasone; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Drug Combinations; Drug Therapy, Combination; Drug Utilization Review; Female; Fluticasone-Salmeterol Drug Combination; Germany; Glucocorticoids; Guideline Adherence; Humans; Male; Middle Aged; Mometasone Furoate; Practice Guidelines as Topic; Practice Patterns, Physicians'; Salmeterol Xinafoate; Young Adult

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Ethanolamines; Forecasting; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Muscarinic Antagonists; Pregnadienediols; Pregnenediones; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

In practice it is logical that inhalers are prescribed only after patients have received training and demonstrated their ability to use the device. However, many patients are unable to use their pressurised metered-dose inhaler devices (pMDIs) correctly. We assessed the relationship between asthma control and patients' ability to use their prescribed pMDIs.. Evaluation of 3,981 (46% male) primary care asthma patient reviews, which included inhaler technique and asthma control, by specialist nurses in primary care in 2009. The paper focuses on people currently prescribed pMDI devices.. Accurate data on reliever and preventer inhaler prescriptions were available for 3,686 and 2,887 patients, respectively. In patients prescribed reliever inhalers, 2,375 (64%) and 525 (14%) were on pMDI alone or pMDI plus spacer, respectively. For those prescribed preventers, 1,976 (68%) and 171 (6%) were using a pMDI without and with a spacer, respectively. Asthma was controlled in 50% of patients reviewed. The majority of patients (60% of 3,686) were using reliever pMDIs, 13% with spacers. Incorrect pMDI use was associated with poor asthma control (p<0.0001) and more short burst systemic steroid prescriptions in the last year (p=0.038). Of patients using beclometasone (the most frequently prescribed preventer drug in our sample), significantly more of those using a breath-actuated pMDI device (p<0.0001) and a spacer (p<0.0001) were controlled compared with those on pMDIs alone.. Patients who are able to use pMDIs correctly have better asthma control as defined by the GINA strategy document. Beclometasone via a spacer or breath-actuated device resulted in better asthma control than via a pMDI alone. Patients prescribed pMDIs should be carefully instructed in technique and have their ability to use these devices tested; those unable to use the device should be prescribed a spacer or an alternative device such as one that is breath-actuated.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Patient Education as Topic; Pregnadienediols; Retrospective Studies; Self Administration; Treatment Outcome; Young Adult

National asthma treatment guidelines recommend low/medium-dose inhaled corticosteroids (ICSs) as initial therapy in mild asthma patients. However, low doses of a fixed-dose combination of ICS and long-acting β-agonists are sometimes used. This study compares asthma-related outcomes and health care utilization and costs in clinical practice in patients starting fluticasone propionate 100 μg and salmeterol 50 μg via Diskus (FSC) or mometasone furoate (MF).. A retrospective cohort study was conducted to compare asthma-related outcomes in asthma patients who received FSC or MF, using a large health insurance claims dataset spanning January 2004-December 2008. Patients with ≥1 claim with an asthma ICD-9-CM diagnosis code and ≥2 FSC or MF prescriptions were included, stratified into FSC or MF groups by study drug received first and matched using propensity score.. A total of 18,283 patients met inclusion criteria (14,044 FSC and 4239 MF); 3799 matched pairs were identified (mean follow-up: FSC 548 days, MF 537 days). FSC patients had lower risk of asthma-related exacerbation (Hazard ratio = 0.88, 95% CI 0.81-0.95, p = .002), defined as either asthma-related emergency department (ED) visits/hospitalizations or receipt of systemic corticosteroids (SCSs); fewer SCS claims (mean 0.28 vs. 0.33, p = .021); and fewer asthma-related physician office (PO) and hospital outpatient (HO) visits (mean 1.17 vs. 1.63, p < .001). However, asthma-related ED visits were higher with FSC (p = .004), and FSC patients had higher total costs of asthma-related health care ($953 vs. $862, p = .002).. In asthma patients initiating ICS therapy, MF had lower asthma-related ED visits. However, FSC may reduce the use of SCS and asthma-related PO/HO visits.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Cohort Studies; Delivery of Health Care; Drug Combinations; Emergency Service, Hospital; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Medication Adherence; Middle Aged; Mometasone Furoate; Pregnadienediols; Proportional Hazards Models; Retrospective Studies; United States; Young Adult

Mometasone furoate (MF)/formoterol fumarate (F) combination is a new inhaIed corticosteroid/long-acting β₂-adrenergic agonist (ICS/LABA). The purpose of this study was to evaluate the effects of different dose combinations of MF/F on a variety of late-phase responses to aerosolized antigen challenge in ovalbumin sensitized Brown Norway rats. Late-phase responses were assessed by reductions in lung function, measured by forced vital capacity (FVC) and increased numbers of inflammatory cells and pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid of ovalbumin challenged rats. Intratracheal administration of MF/F 5 h before aerosolized ovalbumin challenge inhibited the increase in inflammatory cells, including eosinophils and levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor-α (TNF-α) appearing in the bronchoalveolar lavage fluid 24 h after the antigen challenge. The combination index for inhibition of both inflammatory cells and cytokines was consistently <1 suggesting a synergistic interaction between MF and F. Intratracheal MF/F given 24 h after the aerosolized ovalbumin challenge reversed the reduction in FVC with statistically significant effects seen over a 24 h period after drug whereas MF and F alone reversed the antigen-induced reduction in FVC at selected times only. At 5 h after drug administration, when both MF and F were partially active, the combination index for MF/F was <1 suggesting a synergistic interaction between MF and F for reversal of the lung function. These results demonstrate that MF/F combination inhibits a variety of late-phase responses induced by allergen challenge and it is likely that MF/F will have a significant benefit in clinical asthma to suppress lung inflammation and improve lung function.

Topics: Adrenergic beta-2 Receptor Agonists; Allergens; Animals; Anti-Inflammatory Agents; Asthma; Cytokines; Drug Therapy, Combination; Eosinophils; Ethanolamines; Formoterol Fumarate; Male; Mometasone Furoate; Neutrophils; Pregnadienediols; Rats; Rats, Inbred BN; Vital Capacity

This article provides evidence on the psychometric properties of the Asthma Control Questionnaire (ACQ) in adolescent and adult patients with persistent asthma treated with a combination of inhaled glucocorticoid and long-acting beta2-agonist (LABAs), and explores the factors associated with important improvements in asthma control.. Data from patients in two large (n = 737 and 772) Phase III, randomized, double-blind, parallel-group, multi-center, placebo-controlled studies of mometasone furoate/formoterol fumarate (MF/F) combination formulation compared with monotherapies in subjects with persistent asthma previously treated with either low- or medium-dose inhaled glucocorticoids were used to evaluate the ACQ psychometric properties and predictors of important ACQ improvement, defined as an ACQ score decline from baseline of 0.5 or more at the end of treatment.. With 15% and 8% participation from adolescents in the low- and medium-dose studies, the ACQ yielded acceptable reliability (intraclass correlation coefficient ≥ 0.75), and baseline and change scores demonstrated moderate to strong correlations with other baseline measures and change scores in other measures of asthma-related health, including the Asthma Quality of Life Questionnaire (AQLQ12+) domains and total scores. More MF/F treatment group patients (48%) achieved an important ACQ change at 26 weeks compared with MF (32%), F (26%), and placebo (18%) treatment groups (p < .001). Use of rescue medications before randomization was a significant predictor of important ACQ improvement in both studies.. These findings support the psychometric properties of the ACQ to measure asthma control among persistent asthma patients and provide confidence in the significant improvements in asthma control demonstrated by the MF/F treatment group.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Mometasone Furoate; Peak Expiratory Flow Rate; Pregnadienediols; Psychometrics; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Vital Capacity

To evaluate the clinical efficacy and safety of mometasone furoate administered via a dry powder inhaler (MF-DPI) in Japanese patients with intermittent or mild persistent asthma who were not previously receiving inhaled corticosteroids.. This was an 8-week open-label study conducted in Japanese patients > or =16 years of age with intermittent or mild persistent asthma. All patients provided informed written consent before baseline and were treated with MF-DPI 200 microg/day, taken as 100 microg twice daily (BID). Inhaled steroids other than the study drug are not used, the drugs used previously are continued, dose of concomitant drug may be reduced if symptoms are improved and no new drugs were allowed during the trial. The primary efficacy variable was the change from baseline in morning peak expiratory flow (AM PEF). Secondary efficacy variables were evening (PM) PEF, spirometric measurements of lung function, and subjective symptoms. Descriptive statistics and standard errors were calculated for each efficacy evaluation. The safety of MF-DPI treatment was evaluated by measuring adverse events (AEs) and laboratory tests.. Twenty patients received MF-DPI, and 19 patients (nine with intermittent asthma and 10 with mild persistent asthma) were included in the full analysis set (FAS). The mean AM PEF and PM PEF values increased by 9.1% (P < 0.0001) and 7.3% (P < 0.0001), respectively, in the FAS. Improvements in AM and PM PEF occurred as early as week 1 and were sustained throughout treatment. Improvements at week 8 in forced expiratory volume in 1 second and forced vital capacity were 11.0% and 8.2%, respectively. Notable decreases occurred for subjective symptom scores. The reported AEs were mild to moderate in severity. Study limitations include the small sample size and open-label treatment. This study was planned as the first study of MF-DPI in Japanese mild asthma patients without receiving other inhaled steroids. In addition, the cost:benefit ratio of MF-DPI in patients with intermittent asthma was not addressed.. MF-DPI 100 microg BID is an effective treatment for Japanese patients with intermittent or mild persistent asthma.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Female; Humans; Japan; Male; Middle Aged; Mometasone Furoate; Patient Compliance; Peak Expiratory Flow Rate; Pregnadienediols; Treatment Outcome; Young Adult

Retrospective database study comparing upper and lower airway-related outcomes for patients with rhinitis and co-morbid asthma receiving mometasone furoate--an intranasal corticosteroid with low systemic bioavailability--or an oral antihistamine.. 395 patients prescribed intranasal mometasone were matched on 10 demographic and respiratory-related criteria in a 1:2 ratio to 790 patients prescribed oral antihistamine. Asthma and rhinitis control were assessed over one year using predefined composite proxy measures.. Asthma control was achieved by 309/395 (78.2%) versus 580/790 (73.4%; p=0.071) patients in the mometasone and antihistamine cohorts, respectively. Rhinitis control was achieved by 293 (74.2%) versus 539 (68.2%; p=0.035), respectively. The adjusted odds ratios for antihistamines, relative to mometasone, were 0.71 (95% CI, 0.52-0.98) for achieving asthma control and 0.74 (95% CI, 0.56-0.97) for achieving rhinitis control.. Patients with rhinitis and co-morbid asthma initiating rhinitis therapy achieved significantly better upper as well as lower airway outcomes with intranasal mometasone than with oral antihistamine.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Asthma; Case-Control Studies; Child; Child, Preschool; Confidence Intervals; Female; Histamine Antagonists; Humans; Infant; Logistic Models; Male; Middle Aged; Mometasone Furoate; Odds Ratio; Pregnadienediols; Retrospective Studies; Rhinitis; Treatment Outcome; Young Adult

Because adherence to asthma controller medication among adolescents and young adults is poor but critical for asthma control, strategies are needed to improve adherence. One strategy is to reduce the number of daily doses necessary to maintain adequate control. Mometasone furoate delivered through a dry powder inhaler (MF-DPI) is an inhaled corticosteroid (ICS) approved for once-daily dosing in most patients. Fluticasone propionate (FP) is an ICS approved for twice-daily dosing. A retrospective claims analysis was performed to assess treatment adherence and markers of asthma control in adolescent and young adult patients with mild asthma who began treatment with MF-DPI or FP.. Data from approximately 37 million patients in an administrative insurance claims database in the United States were analyzed. Patients, 12-25 years, with mild asthma and previous asthma medication use were assigned an index date based on their first prescription fill of MF-DPI or FP between 1 January 2005 and 10 October 2008. Demographics, prescription claims, and health care utilization data were captured in the 365-day period before (preindex) and after (postindex) the index date. Patients from each cohort were propensity score-matched 1:1 based on preindex data. Adherence was measured by prescription fills and percentage of days covered (PDC); asthma control was measured by exacerbations and short-acting β₂-agonist (SABA) canister claims. Bivariate and multivariate generalized linear model (GLM) analyses were conducted to determine differences in outcomes between the cohorts.. After matching, 692 patients per group (average age - 16 years) were analyzed. Adherence in the postindex period was significantly higher in the MF-DPI cohort compared with the FP cohort as measured by PDC (23.5% vs. 14.5%; p< .0001) and prescription fills (2.70 vs. 1.91; p< .0001). The mean number of postindex SABA canister claims was significantly lower in the MF-DPI cohort compared with the FP cohort (1.04 vs. 1.40; p< .0001). There was no significant difference in the mean number of postindex exacerbations between the cohorts.. Adolescent/young adult patients with mild asthma who received MF-DPI had better postindex adherence and fewer SABA canister claims than patients receiving FP.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Cohort Studies; Comorbidity; Female; Fluticasone; Humans; Insurance Claim Review; Male; Medication Adherence; Mometasone Furoate; Pregnadienediols; Retrospective Studies; Socioeconomic Factors; United States; Young Adult

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Drug Combinations; Drug Costs; Drug Interactions; Ethanolamines; Formoterol Fumarate; Humans; Metered Dose Inhalers; Mometasone Furoate; Mometasone Furoate, Formoterol Fumarate Drug Combination; Pregnadienediols; Treatment Outcome

Although current National Asthma Education and Prevention Program (NAEPP) guidelines indicate low-dose inhaled corticosteroid (ICS) monotherapy as the preferred treatment for patients with mild persistent asthma, many patients receive ICS and long-acting beta(2)-agonist (LABA) combinations. The objective of the current study was to evaluate asthma-related charges in patients with mild asthma who began treatment with mometasone furoate (MF) versus those who began treatment with a fluticasone propionate/salmeterol (FPS) combination.. This retrospective administrative claims database analysis collected data from the 365-day periods before (preindex period) and after (postindex period) the study index date from patients with mild asthma aged 12 to 65 years who began treatment with MF or FPS. Asthma-related inpatient, outpatient, pharmaceutical, and total charges; exacerbations; short-acting beta(2)-agonist (SABA) canister claims; and adherence to therapy were assessed. Matched cohorts of MF and FPS patients were compared using multivariate generalized linear regression models.. Among matched MF (n = 4094) and FPS (n = 4094) cohorts, MF patients had significantly lower postindex asthma-related total charges ($2136 vs $2315, respectively; P = 0.0003), lower pharmaceutical charges ($727 vs $925, respectively; P < 0.0001), fewer exacerbations (0.14 vs 0.16, respectively; P = 0.0306), fewer SABA canister claims (0.9 vs 1.0, respectively; P < 0.0001), and greater adherence measured by prescription fills (3.0 vs 2.8, respectively; P < 0.0001). Asthma-related inpatient charges, outpatient charges, and adherence measured by percent of days covered were not significantly different between treatment cohorts. Limitations included a lack of additional ICS and ICS/LABA therapies, a lack of pediatric patients, and the general limitations associated with retrospective database analyses (e.g., no patient records).. These data suggest that MF may be more cost-effective than FPS for the treatment of mild asthma. To effectively and efficiently manage asthma, it is important for clinicians to follow current NAEPP guidelines, which indicate ICS monotherapy as preferred treatment for mild persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Case-Control Studies; Child; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Health Resources; Humans; Male; Middle Aged; Mometasone Furoate; Multivariate Analysis; Pregnadienediols; Retrospective Studies; Young Adult

A decrease in nasal nitric oxide (NO) and an increase in exhaled NO have been demonstrated in patients with nasal polyposis (NP).. The aims were to evaluate the flux of NO from the three compartments of the respiratory tract, namely, upper nasal, lower conducting and distal airways, and to search for relationships between NO parameters and indexes of upper and lower disease activity (bronchial reactivity and obstruction). The effect of medical treatment of polyposis was also evaluated.. Seventy patients with polyposis were recruited. At baseline, pulmonary function tests (spirometry, plethysmography, bronchomotor response to deep inspiration using forced oscillation measurement of resistance of respiratory system, methacholine challenge, multiple flow rates of exhaled NO and nasal NO measurements) were performed together with an assessment of polyposis [clinical, endoscopic and computed tomography (CT) scores].. Statistical relationships were demonstrated between nasal NO flux and severity scores (clinical: rho=-0.31, P=0.015; endoscopic: rho=-0.57, P<0.0001; CT: rho=-0.46, P=0.0005), and between alveolar NO concentration and distal airflow limitation (FEF(25-75), rho=-0.32, P=0.011). Thirty-six patients were assessed after 11 [7-13] (median [interquartile]) months of medical treatment, demonstrating an improvement in clinical and endoscopic scores, an increase in nasal NO flux, a decrease in NO flux from conducting airways, an improvement in the mild airflow limitation (forced expiratory volume in 1 s, FEF(25-75), even in non-asthmatic patients) and a decrease in the bronchoconstrictor effect of deep inspiration.. The medical treatment of NP improves both airway reactivity and obstruction, whatever the presence of asthma, suggesting a functional link between upper and lower airway functions.

Topics: Adult; Airway Obstruction; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Nitric Oxide; Prednisolone; Pregnadienediols; Respiratory System; Spirometry

Topics: Anti-Allergic Agents; Asthma; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Hippocratic Oath; Humans; Mometasone Furoate; Pregnadienediols

Topics: Administration, Inhalation; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Humans; Mometasone Furoate; Periodicals as Topic; Pregnadienediols; Treatment Outcome

A 60-year-old man developed a bullous contact dermatitis after topical corticosteroid treatment of dermatitis on his lower leg. Subsequent patch testing showed cross-reactions to numerous group B and group D corticosteroids as well as cross-reactions to group C desoximetasone and group D1 mometasone furoate. His patch-test result was negative for the group A corticosteroids hydrocortisone and tixocortol pivalate. We discuss the uncommon finding of cross-reactions to desoximetasone and mometasone furoate.

Topics: Administration, Cutaneous; Anti-Inflammatory Agents; Asthma; Cross Reactions; Dermatitis, Allergic Contact; Desoximetasone; Diagnosis, Differential; Humans; Leg; Male; Middle Aged; Mometasone Furoate; Patch Tests; Pregnadienediols; Rhinitis, Allergic, Seasonal

Topics: Anti-Allergic Agents; Asthma; Child; Drug Therapy, Combination; Glucocorticoids; Histamine H1 Antagonists; Humans; Loratadine; Mometasone Furoate; Pregnadienediols; Quality of Life; Rhinitis, Allergic, Seasonal

Treatment of asthma with corticosteroids results in downregulation of eosinophilic airway inflammation. We evaluated in vitro the activity of an "inhaled" corticosteroid, mometasone furoate (MF), and of a "systemic" corticosteroid, dexamethasone (DEX), on eosinophil functions, i.e. adhesion molecule expression and cell chemotaxis. Partially purified blood eosinophils were obtained from 18 asthmatic subjects sensitized to house dust mites. The expression of the macrophage antigen (Mac)-1 (CD11b/CD18) was measured by specific monoclonal antibody (mAb) staining and flow cytometry analysis at baseline or after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or with recombinant human (rh) granulocyte macrophage-colony stimulating factor (GM-CSF) plus a mAb anti-human (ah) IgE low affinity receptor [FcepsilonRII or CD23]. Cell chemotaxis toward the complement fragment 5a (C5a) or rh interleukin (IL)-5 was evaluated in Boyden microchambers by light microscopy. Eosinophils showed a significant increase in Mac-1 expression after activation with fMLP or with rh GM-CSF plus ah CD23 mAbs (p<0.05, each comparison) and a remarkable chemotactic response to both C5a or rh IL-5 (p<0.001, each comparison). To test the inhibitory activity of MF and DEX on eosinophil functions, the cells were preincubated for 3 h with four concentrations (0.1, 1, 10 and 100 nM) of each of the two drugs, before being activated by fMLP or by rh GM-CSF plus ah CD23 mAbs or tested with C5a or with rh IL-5. Independently of the stimulus used, both Mac-1 expression and eosinophil migration were effectively downregulated by preincubation with MF or DEX at 1, 10 and 100 nM (p<0.05). The inhibitory activity on cell chemotaxis in response to both C5a or with rh IL-5 was higher for MF than DEX, but only at the highest concentration tested (p<0.05, each comparison). These data demonstrate that concentrations of MF similar to those obtained in vivo are highly effective in inhibiting eosinophil functions involved in airway inflammation.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Animals; Asthma; Cell Adhesion Molecules; Chemotaxis, Leukocyte; Child; Dexamethasone; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Dust; Eosinophils; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-5; Italy; Macrophage-1 Antigen; Men; Mites; Mometasone Furoate; N-Formylmethionine Leucyl-Phenylalanine; Pregnadienediols; Recombinant Proteins; Women

Topics: Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Mometasone Furoate; Nebulizers and Vaporizers; Pregnadienediols

Topics: Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Humans; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols