Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.

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.     

Comparable morning versus evening administration of once-daily mometasone furoate dry powder inhaler

BACKGROUND: The control of daytime and nighttime symptoms is an important measure of effectiveness of asthma therapy, especially, when administered once-daily. OBJECTIVE: To evaluate the efficacy of evening and morning administrations of mometasone furoate administered via a dry powder inhaler (MF-DPI) 400mug once-daily (QD) to show equivalence. METHODS: Open-label, randomized, parallel-group study in adult patients with mild to moderate asthma with a >/=3-month history of ICS use. Patients received MF-DPI 400mug 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. RESULTS: 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 400mug 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. CONCLUSIONS: This open-label study did not identify differences between morning and evening dosing of MF-DPI 400mug QD. A better effect of evening dosing compared to morning dosing found in previous double-blind placebo-controlled studies could not be confirmed.     

The efficacy and safety of mometasone furoate delivered via a dry powder inhaler for the treatment of asthma.

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.     

Comparison of the efficacy and safety of mometasone furoate dry powder inhaler to budesonide Turbuhaler.

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.     

Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma

Objective: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. Methods: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥12 years with persistent asthma received placebo MDPI or albuterol MDPI 180?µg (2 inhalations?×?90?µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180?μg (2 inhalations?×?90?μg/inhalation) as needed (PRN). Results: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n?=?333) than albuterol MDPI (40%; n?=?321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β₂-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. Conclusions: The safety profile of albuterol MDPI 180?μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma.     

Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate

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.     

Budesonide turbuhaler delivered once daily improves health-related quality of life in adult patients with non-steroid-dependent asthma.

Budesonide inhalation powder via the dry-powder multidose inhaler Turbuhaler (budesonide Turbuhaler) has been shown to improve lung function and symptoms in adults with asthma. In this double-blind, placebo-controlled, multicenter trial, we evaluated the effects of once-daily budesonide Turbuhaler on health-related quality of life (HRQL) in 177 adults (aged 18-70 years) with non-steroid-dependent asthma. Patients were randomized to receive budesonide Turbuhaler (400 micrograms) once daily or placebo for 12 weeks. HRQL was assessed at baseline and weeks 4 and 12 using the Asthma Quality of Life Questionnaire (AQLQ). In addition to assessment based on the four AQLQ domains (activity limitations, asthma symptoms, emotional function, and response to exposure to environmental stimuli), AQLQ overall scores were analyzed for both treatment groups. Compared with placebo, patients using budesonide Turbuhaler once daily had statistically significant (p < 0.001) improvements from baseline to weeks 4 and 12 in AQLQ overall scores. Statistically significant improvements from baseline to weeks 4 and 12 in all four individual domains also were observed in the budesonide Turbuhaler group compared with placebo. Differences between the two treatment groups in mean changes from baseline in AQLQ overall, asthma symptoms, and emotional function reached the level required for patients to achieve a minimal important difference of change (> or = 0.5 U) at week 12. A retrospective analysis of the data showed that approximately 70% of patients treated with budesonide Turbuhaler experienced a minimal important difference of change in AQLQ overall scores. Overall, improvements in AQLQ correlated significantly (p < or = 0.04) with improvements in forced expiratory volume in 1 second, morning peak expiratory flow measurements, asthma symptoms, and breakthrough bronchodilator use at the study end. Thus, patients with corticosteroid-na?ve asthma can experience improved HRQL when using budesonide Turbuhaler.     

Comparable efficacy and tolerability of formoterol (Foradil) administered via a novel multi-dose dry powder inhaler (Certihaler) or the Aerolizer dry powder inhaler in patients with persistent asthma

BACKGROUND: For maximum treatment compliance there is a need to provide asthma patients with devices that suit their particular preferences. The Foradil Certihaler is a novel multi-dose dry powder inhaler developed to increase the choice of devices available. OBJECTIVES: To evaluate the safety and efficacy of formoterol administered via the Foradil Certihaler, or via the single-dose inhaler Foradil Aerolizer. METHODS: This was a randomized, placebo-controlled, double-dummy, incomplete block crossover, dose-ranging and pharmacokinetic study in patients with persistent asthma. Sixty-seven patients (mean 48.0 years) were randomized to formoterol 5, 10, 15 and 30 microg twice daily via the Certihaler, 12 microg formoterol b.i.d. via the Aerolizer, or placebo in four 1-week double-blind treatment periods separated by 1-week single-blind washouts. RESULTS All formoterol doses delivered via the Certihaler or the Aerolizer significantly increased FEV(1) compared with placebo (p < 0.0001). Formoterol demonstrated an onset of action of <3 min. All active treatments were well tolerated. Tremor was the most common adverse event and was more pronounced at high doses. At lower doses the incidence of tremor with the Certihaler was similar to that observed with placebo or the Aerolizer. The pharmacokinetic evaluation comprised 41 patients (mean 45.9 years). Urinary excretion of unchanged formoterol and total formoterol increased with dose delivered via the Certihaler. The optimum dose of formoterol via the Certihaler was 10 microg. Conclusion: Delivery of formoterol via the Certihaler or Aerolizer combines rapid relief with enduring control and provides convenient bronchodilation in patients with persistent asthma.     

Gender differences in health-related quality of life among patients with asthma.

This study has a twofold objective: 1) to explore to what extent suffering from asthma affects the HRQL of men and women differently at several stages of disease severity and 2) to analyze whether the informed poorer HRQL of asthmatic women is related to their higher scores on instruments measuring emotionally disordered symptoms. One hundred fifty-one outpatient asthmatics (84 women and 67 men) completed the Spanish versions of the Asthma Quality of Life questionnaire (AQL), as well as anxiety and depression inventories. A full history, physical examination, and pulmonary function test were performed on all subjects. Patients were classified into one of four asthma severity categories following the criteria of the Global Initiative on Asthma (GINA). There were no gender differences in sociodemographic variables, asthma duration, GINA, FEV1 or dyspnea. However, women showed a poorer HRQL than men, as well as high degrees of anxiety and depression. When these data were reanalyzed taking into account the four groups of asthma severity, women only reported a poorer HRQL than men at the intermittent asthma level. The gender differences on depression and anxiety scores were maintained at the three lower severity levels, but not at the most severe asthma degree. When depression and anxiety scores were partialed out, the AQL scores maintained significant relationships with asthma severity, dyspnea, and FEV1, both in women and men. Therefore, only in men were there also relationships among AQL and sociodemographic data. The best predictor of the women's HRQL was the dyspnea score, whereas in men it was the asthma severity (GINA).     

Periodontal surgery improves oral health-related quality of life in chronic periodontitis patients in Asian population

The effect of periodontal surgery on patients' quality of life was investigated. Sixty patients received regenerative surgery or resective osseous surgery. Oral health-related quality of life and health-related quality of life instruments were used to assess the participants' quality of life before surgery and 4 weeks after surgery. Periodontal surgery can improve patients' quality of life by alleviating the physical pain and psychological discomfort. The scores were lower (more favorable) in the regenerative surgery group, and the functional limitations of the regenerative surgery group improved substantially compared with those of the resective osseous surgery group (P = 0.0421). The patients' oral health-related quality of life scores improved significantly after periodontal surgery. Clinicians can take advantage of the positive functional oral health-related quality of life impacts of regenerative surgery.     

Levocetirizine improves health-related quality of life and health status in persistent allergic rhinitis

BACKGROUND: Allergic rhinitis is a chronic respiratory disorder with a detrimental impact on health-related quality of life (HRQOL) and health status. Enhancement and maintenance of patient function and well-being are therefore considered as essential. OBJECTIVE: To determine whether long-term treatment with levocetirizine 5mg improves HRQOL and health status in persistent allergic rhinitis (PER) patients assessed with RQLQ and SF-36 scales over a 6-month period. METHODS: The Xyzal in PER Trial (XPERT) was a multi-center, double-blind, parallel-group study. A total of 551 patients were randomized to receive levocetirizine 5mg or placebo once daily for 6 months and assessed for symptoms, HRQOL (Rhinoconjunctivitis Quality of Life Questionnaire: RQLQ) and health status (SF-36). Sensitivity of the RQLQ and SF-36 to disease severity was tested to ensure their suitability for use in PER patients. Treatment effect was assessed by means of repeated measures analyses. RESULTS: Over the 6-month treatment period, levocetirizine showed statistically significant improvements over placebo in HRQOL (P < 0.001 for all RQLQ domains and overall scores) and health status (P < or = 0.004 for SF-36 physical and mental summary scores; P < 0.05 for all SF-36 scales). The relative improvement of levocetirizine over placebo exceeded the predefined clinically meaningful threshold of 30% for all RQLQ scores and the improvement from baseline was 3 times the established MID for RQLQ. CONCLUSION: The RQLQ and SF-36 could be used to measure HRQOL and health status in PER patients. Long-term treatment with levocetirizine provides sustained improvement of HRQOL and reduces disease burden in PER patients.     

The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK.

INTRODUCTION: The objective of this study was to report the impact of exacerbations on health-related quality of life (HRQL) and health utility in patients with moderate to severe asthma (BTS levels 4 & 5) in the UK. MATERIALS AND METHODS: Prospective data regarding HRQL were collected (n=112) using the EQ-5D, mini Asthma Quality of Life Questionnaire (mAQLQ), and Asthma Symptom Utility (ASUI) measures. RESULTS: The mAQLQ, EQ-5D and ASUI were all significantly worse for patients suffering exacerbations (p<0.001) compared to those without. There was also evidence of a further HRQL decrement in those patients who had been admitted to hospital as a result of an exacerbation during the four-week study. CONCLUSIONS: This study documents the impact of asthma exacerbations on HRQL in patients with moderate to severe asthma. There was some evidence of floor effects on the mAQLQ and ASUI in their ability to capture the impact of exacerbations. These study data are suitable for use in economic evaluations.     

The relationship between health-related quality of life, lung function and daily symptoms in patients with persistent asthma

It is generally believed that there is a direct correlation between asthma control and a patient's health-related quality of life (HRQL). Objective and subjective measures of asthma control are used interchangeably. A retrospective analysis from 8994 patients from 27 randomized, controlled clinical trials with persistent asthma was conducted to determine the degree of association which exists between objective (lung function) and subjective (symptoms, quality of life) measures. Assessments were made via forced expiratory volume in 1-second (FEV1), self-reported symptoms and the Asthma Quality of Life Questionnaire (AQLQ) overall scores. Baseline percent predicted FEV1 was weakly correlated with baseline symptom-free days (SFD) and baseline overall AQLQ scores (r=0.11 and 0.09, respectively; P <0.001). Changes in percent predicted FEV1 correlated weakly with changes in SFD but was more strongly correlated with changes in overall AQLQ scores (r= 0.26 and 0.38, respectively; P <0.001). Additionally, SFD at both baseline and endpoint were moderately correlated with overall AQLQ scores at baseline and endpoint (r=0.36 and 0.44; P <0.001). This study suggests that the impact of asthma on a patients' HRQL is not fully accounted for by objective measures such as lung function. Thus, HRQL data complements rather than duplicates results from traditional, objective assessments of asthma control.