Fluticasone Propionate In Patients Research Articles

Variability in Swallowed Topical Corticosteroid Practice Patterns for Treatment of Pediatric Eosinophilic Esophagitis.

Given the variety of preparations and lack of standardization of swallowed topical corticosteroids (STC) for treatment of eosinophilic esophagitis (EoE), we sought to better understand STC prescribing practices of pediatric gastroenterologists. A 12-question survey was distributed to members of NASPGHAN Eosinophilic Gastrointestinal Disease Special Interest Group (EGID SIG) and responses were analyzed. Forty-two of 68 physicians responded. Oral viscous budesonide (OVB) was overall first choice STC in 31 (74%) survey respondents, with OVB most frequently utilized in patients under 5 years-old and fluticasone propionate (FP) in patients 13-18 years-old. Nineteen types of mixing vehicles were used for OVB preparation, the three most frequent being sucralose, honey, and artificial maple syrup. Insurance coverage, cost, and patient compliance were most frequently cited barriers to STC use. Highly variable STC prescribing practices reported by this group highlights the need for standardization of STC treatment in EoE.

Fluticasone furoate/vilanterol versus fluticasone propionate in patients with asthma and exercise-induced bronchoconstriction

Objective: To investigate whether once-daily (OD) fluticasone furoate (FF)/vilanterol (VI) provides greater long-term protection from postexercise fall in forced expiratory volume in 1 s (FEV1) than twice-daily (BD) fluticasone propionate (FP) in patients with asthma and exercise-induced bronchoconstriction. Methods: A randomized, double-blind, crossover study was conducted in patients (aged 12–50 years) on low-/mid-dose maintenance inhaled corticosteroid. Following a 4-week run-in period (FP 250 µg BD), patients with a ≥ 20% decrease in postexercise FEV1 received FF/VI 100/25 µg OD or FP 250 µg BD for 2 weeks. Exercise challenges were carried out 23 h after the first dose of study medication, and 12 and 23 h after evening clinic dose at the end of the 2-week treatment period. After a 2-week washout period (FP 250 µg), patients crossed over treatments, with procedures and tests repeated. The primary endpoint was mean maximal percentage decrease from pre-exercise FEV1 following exercise challenge 12-h postevening dose on Day 14. Results: The mean maximal percentage decrease from pre-exercise FEV1 after the 12-h exercise challenge (Day 14) was 15.02% with FF/VI, and 16.71% with FP (difference, −1.69; 95% confidence interval, −3.76 to 0.39; p = 0.109). After the 23-h exercise challenge (Day 14), respective mean maximal decreases were 11.90% and 14.05% (difference, −2.15; 95% confidence interval, −4.31 to 0.01). Conclusion: The study failed to show a difference between FF/VI and FP at providing long-term protection from exercise-induced bronchoconstriction.

Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease.

The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of −0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis.

Histological Response to Fluticasone Propionate in Patients With Eosinophilic Esophagitis Is Associated With Improved Functional Esophageal Mucosal Integrity.

The esophageal mucosal integrity is impaired in patients with eosinophilic esophagitis (EoE). We aimed to evaluate the effect of fluticasone propionate on inflammation and functional and structural markers of esophageal mucosal barrier integrity in adult patients with EoE. In this prospective study, we included 15 EoE patients (median age (IQR), 43 (30-45) years). Patients underwent upper endoscopy before and after an 8-week course of swallowed fluticasone propionate 500 μg BID. Several parameters of esophageal mucosal barrier integrity were evaluated: esophageal electrical tissue impedance in vivo during endoscopy, transepithelial electrical resistance (TER) and transepithelial molecule flux in Ussing chambers using esophageal biopsy specimens, and intercellular spaces as a structural marker of permeability using electron microscopy. Esophageal eosinophils and mast cells were counted, and expression of inflammatory cytokines and barrier integrity proteins was investigated using qPCR. Esophageal symptoms and signs were also assessed. Peak eosinophil and mast cell counts decreased significantly after fluticasone propionate treatment. The esophageal mucosal integrity increased substantially during treatment, as shown by increased extracellular impedance and TER (both P<0.01) and decreased transepithelial molecule flux in Ussing chambers (P<0.05). Whereas expression of genes encoding for inflammatory cytokines (IL5, IL13, eotaxin-3, periostin, TSLP) decreased after treatment, expression of genes encoding for barrier integrity proteins (filaggrin and desmoglein-1) increased. Fluticasone propionate treatment decreases eosinophilic inflammation and improves the esophageal mucosal barrier integrity in adult EoE patients. Improvement of the mucosal barrier integrity correlates with normalization of expression of desmoglein-1 and filaggrin marker genes.

Adding salmeterol to fluticasone propionate or increasing the dose of fluticasone propionate in patients with asthma

The National Asthma Education and Prevention Program guidelines recommend two options for patients uncontrolled on inhaled corticosteroid (ICS) alone: add a long-acting bronchodilator or increase the dose of the ICS. The purpose of this study was to compare asthma-related exacerbations and asthma control in asthma patients receiving fluticasone propionate (FP) monotherapy with an increased dose of FP compared with maintaining the dose and adding salmeterol (SAL) via a single device (FP/SAL combination [FSC]). A retrospective observational study was performed using health insurance claims spanning from January 2001 to August 2006 ("study period"). Subjects were > or =12 years of age, with asthma (International Classification of Diseases [ICD] 493.xx), and were stepped up from FP 44 microg to either FP 110 microg (FP110) or FP 100 microg/SAL 50 microg (FSC), or from FP110 to either FP 220 microg or FP 250 microg/SAL 50 microg (FSC). There were 1744 subjects identified, 557 (32%) increased FP and 1187 (68%) added SAL. The cohorts were relatively similar, and after adjusting for baseline characteristics, patients who added SAL to their same dose of FP had 41% lower odds of an asthma exacerbation (odds ratio = 0.59; 95% confidence interval [CI] = 0.46-0.76; p < 0.001), 36% fewer prescriptions for a short-acting beta-agonist (rate ratio = 0.64; 95% CI = 0.58-0.70; p < 0.001), and a 32% increase in ICS refill persistence compared with increasing the dose of FP. In asthma patients who are not adequately controlled with ICS (FP), adding SAL as FSC is associated with lower risk of an asthma-related exacerbation and better asthma control compared with increasing the dose of ICS (FP).

Glucocorticoid-regulated genes in eosinophilic esophagitis: A role for FKBP51

Eosinophilic esophagitis (EE) involves marked accumulation of eosinophils in the esophageal mucosa that responds to swallowed fluticasone propionate (FP) in a subset of patients. We aimed to uncover the mechanism of action of swallowed FP in patients with EE by providing evidence for a topical effect in the esophagus by identifying a molecular signature for FP exposure in vivo. Global microarray expression profiles, immunofluorescence microscopy, and cell signaling in esophageal tissue and cell lines were analyzed. Thirty-two transcripts exhibited altered expression in patients who responded to swallowed FP treatment. Esophageal FK506-binding protein 5 (FKBP51) mRNA levels were increased (P < .05) in FP responders compared with those seen in control subjects and patients with untreated active EE. After FP treatment of esophageal epithelial cells, FKBP51 mRNA and protein levels were increased in a dose- and time-dependent manner by FP treatment in vitro. FP-induced FKBP51 was steroid receptor dependent because RU486 completely inhibited gene and protein induction. The half-life of FKBP51 mRNA was 16 to 18 hours independent of FP treatment. FKBP51 overexpression reduced FP action as assessed by FP inhibition of IL-13-induced eotaxin-3 promoter activity. Our results suggest that swallowed glucocorticoid treatment directly affects esophageal gene expression in patients with EE. In particular, increased FKBP51 transcript levels identify glucocorticoid exposure in vivo and distinguish FP responders from untreated patients with active EE and patients without EE. In addition, FKBP51 reduces glucocorticoid-mediated inhibition of IL-13 signaling in epithelial cells in vitro, suggesting that FKBP51 might influence FP responsiveness. We propose that esophageal FKBP51 levels have diagnostic and prognostic significance in patients with EE.

Determinants of response to fluticasone propionate and salmeterol/fluticasone propionate combination in the Gaining Optimal Asthma controL study

During the Gaining Optimal Asthma controL study, 3416 patients with uncontrolled asthma were randomized to receive salmeterol/fluticasone propionate combination (SFC) or fluticasone propionate (FP) for 1 year. Approximately two thirds of patients achieved well-controlled (WC) asthma, and one third continued to have asthma that was not well controlled (NWC). This analysis aimed to (1) identify factors influencing treatment response and (2) assess the clinical benefits of SFC and FP in patients with NWC asthma. Logistic regression analysis was used to investigate whether covariates influenced the achievement of at least WC asthma in the study population. In patients with NWC asthma, predefined criteria were used to assess improvements in 6 clinical outcomes. Factors affecting the probability of having NWC asthma included smoking status (current vs never: odds ratio [OR], 2.757; 95% CI, 2.061-3.689; P < .0001; former vs never: OR, 1.274; 95% CI, 1.031-1.574; P = 0.0273), sex (women vs men: OR, 0.652; 95% CI, 0.527-0.806; P < .0001), history of inhaled corticosteroid use (no history vs history: OR, 0.546; 95% CI, 0.437-0.683; P < .0001), and treatment (FP vs SFC: OR, 1.972; 95% CI, 1.686-2.308; P < .0001). Of patients with NWC asthma, 86% to 96% showed improvements in 1 or more clinical outcomes. It is imperative for good asthma control that patients stop smoking. Patients who did not have at least WC asthma demonstrated clinical improvements in individual asthma outcomes. Although not all patients can achieve guideline-defined control, long-term treatment with SFC or FP is associated with clinical improvements in nearly all patients, regardless of smoking history or inhaled corticosteroid use.

Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma

Objective To investigate the relative efficacy of ciclesonide and fluticasone propionate (FP) administered at comparable microgram doses in maintaining asthma control in patients with moderate-to-severe persistent asthma. Methods This randomized, open-label, parallel-group study enrolled patients aged 12–75 years with a ⩾6-month history of bronchial asthma. To enter a 2-week run-in period, patients had to have received FP 500–1000 μg/day or equivalent at a stable dose for ⩾4 weeks and have a forced expiratory volume in 1 s (FEV 1) ⩾80% of predicted. To enter the treatment period, patients had to have the following during run-in: FEV 1 ⩾80% of predicted; reversibility of ΔFEV 1 ⩾12% after 200–400 μg salbutamol; and ⩾1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 μg (ex-actuator) or twice-daily FP 330 μg (ex-actuator) for 6 months. Efficacy was assessed by lung function, asthma exacerbations, asthma symptoms and rescue medication use. Patients completed the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Adverse events (AEs), including local oropharyngeal AEs, were recorded. Results 528 patients were randomized (ciclesonide, n=255; FP, n=273). In both groups, FEV 1 was maintained from baseline to study end (mean increase: ciclesonide 11 mL, FP 24 mL; intention-to-treat [ITT] analysis). The least squares mean±standard error of the mean for the treatment difference was −13±29 (95% confidence interval [CI]: −70, 44) in the ITT analysis and −27±34 (95% CI: −93, 40) in the per-protocol (PP) analysis, demonstrating non-inferiority of ciclesonide to FP. Morning, evening and site-measured PEF improved significantly with both treatments (ITT and PP analyses: p<0.05). Six patients receiving ciclesonide and seven receiving FP (ITT analysis) experienced an asthma exacerbation requiring treatment with oral corticosteroids. Both treatments significantly decreased asthma symptom score sum (ITT and PP analyses: p⩽0.0001) and rescue medication use (ITT and PP analyses: p<0.05), with no significant difference between treatments. Both treatments significantly improved overall AQLQ(S) score (ITT and PP analyses: p<0.05). Significantly more patients experienced candidiasis and dysphonia with FP compared with ciclesonide ( p=0.0023). Conclusion Ciclesonide 320 μg and FP 330 μg administered twice daily over 6 months provided similar efficacy in patients with moderate or severe persistent asthma previously well-controlled by high doses of ICS at baseline. Ciclesonide was associated with fewer local AEs than FP.

A randomized study comparing ciclesonide and fluticasone propionate in patients with moderate persistent asthma

To compare the effects of once-daily ciclesonide and twice-daily fluticasone propionate in patients with moderate persistent asthma. Patients aged 12-75 years with moderate bronchial asthma entered a 1-4 week run-in period. For inclusion into the 12-week, randomized, open-label treatment period, patients had to have a forced expiratory volume in 1s (FEV1) of either 60-80% of predicted or 80% of predicted and a defined use of rescue medication and asthma symptoms, depending on previous treatment. Patients received ciclesonide 320 microg once daily (ex-actuator) or fluticasone propionate 200 microg twice daily. Primary efficacy endpoint was change from baseline in FEV1. In total, 474 patients were randomized. FEV1 increased significantly from baseline with ciclesonide and fluticasone propionate in the intention-to-treat (ITT) and per-protocol (PP) analyses (all p < 0.0001). Treatment difference was -31 mL (95% confidence interval [CI]: -121, 59) in the PP analysis, demonstrating non-inferiority of ciclesonide. Similar findings were seen for other measures of lung function. In the ITT population, asthma symptom scores and rescue medication use decreased with both treatments (all p < 0.0001). Improvement in health-related quality of life (HRQoL) from baseline was significantly greater with ciclesonide than fluticasone (p = 0.005; one-sided). There were no cases of oral candidiasis in patients receiving ciclesonide and nine cases (3.8%) in those receiving fluticasone propionate (p = 0.002; one-sided). Treatment with once-daily ciclesonide and twice-daily fluticasone propionate resulted in similar improvements in lung function in patients with moderate persistent asthma. Ciclesonide showed significant improvements in oral candidiasis and HRQoL over fluticasone.

The combination of tiotropium bromide and formoterol improves lung function to a greater extent than salmeterol plus fluticasone propionate in patients with chronic obstructive pulmonary disease

The combination of tiotropium bromide and formoterol improves lung function to a greater extent than salmeterol plus fluticasone propionate in patients with chronic obstructive pulmonary disease

Acoustic rhinometric assessment of nasal obstruction after treatment with fluticasone propionate in patients with perennial rhinitis

Objective: To investigate the effect of fluticasone propionate (FP) on the symptom of nasal obstruction and to assess the correlation between the subjective visual analogue score (VAS) and the objective acoustic rhinometry (AR) measurements. Methods: A prospective study of 45 consecutive patients, 30 males and 15 females with a mean age of 27 years (range: 16–59 years), with moderate/severe symptoms of perennial rhinitis who were treated by FP nasal spray for 4 weeks. AR and VAS were used to evaluate, compare and correlate the efficacy of FP nasal sprays. Results: There was a significant improvement in the VAS post-treatment (3.9) compared with pre-treatment (6.3). There was also a significant increase in the nasal volume (V) and minimum cross-sectional area (MCA) after intranasal FP. Good correlation between the total MCA and total V was noted. Subjective improvements in symptoms did not correlate well with objective measurements as the correlation between VAS and AR was poor. Conclusion: Our study provides subjective and objective evidence on the efficacy of intranasal FP in improving nasal obstruction in perennial rhinitis. AR also proved to be a useful instrument in monitoring the effectiveness of medical therapy for perennial rhinitis.

What to do at step 3 of the asthma guidelines—increase the dose of inhaled corticosteroids or add a long-acting β-agonist drug?

What to do at step 3 of the asthma guidelines—increase the dose of inhaled corticosteroids or add a long-acting β-agonist drug?

Features of this month's Journal

Features of this month's <i>Journal</i>

Comparison of oral montelukast and inhaled fluticasone in the treatment of asthma associated with chronic rhinopolyposis: a single-blind, randomized, pilot study

Background: Rhinopolyposis is considered to be a non-immunoglobulin E-mediated inflammatory condition of the nose and sinuses, often associated with chronic rhinitis and asthma. Inhaled corticosteroids are currently the most commonly used anti-inflammatory agents for the chronic treatment of asthma and rhinopolyposis. Recently, montelukast, a selective cysteinyl leukotriene receptor antagonist indicated for the prophylaxis and treatment of asthma, has been shown to be effective in controlling rhinopolyposis and related symptoms. Objective: The aim of this study was to compare the short-term clinical efficacy of montelukast with that of fluticasone propionate in patients with asthma associated with rhinopolyposis. Methods: In this prospective, single-blind, randomized, pilot study, 12 out-patients with asthma associated with rhinopolyposis were given oral montelukast (10 mg once daily) or inhaled fluticasone propionate (intranasal suspension 50 μg and spray 250 μg twice daily). At baseline and after 30 days of treatment, the patients completed an asthma and rhinitis questionnaire and underwent nasal endoscopy, pulmonary function tests, and bronchial provocation testing. Results: Of the 12 study patients (9 men, 3 women), 7 were randomized to the montelukast group and 5 to the fluticasone group. There were no significant differences in baseline characteristics between the 2 treatment groups. After treatment, improvements in nasal and respiratory symptoms and nasal endoscopy results were found in 6 patients, 3 in each treatment group. No significant differences in the peak expiratory flow rate, forced expiratory volume in 1 second, or bronchial hyperresponsiveness changes after treatment were observed between the 2 groups. Conclusions: Our preliminary data show a comparable effect on respiratory and nasal symptoms and pulmonary function test results between oral montelukast and inhaled fluticasone in this small patient population, suggesting that leukotriene-receptor antagonists might be considered an alternative to inhaled corticosteroids in the treatment of asthma associated with rhinopolyposis.

Loss of response to treatment with leukotriene receptor antagonists but not inhaled corticosteroids in patients over 50 years of age

There are limited published data describing the relative efficacy of available treatment options in younger versus older patients with persistent asthma. To compare the efficacy of fluticasone propionate (FP) and zafirlukast (Z) in younger (12 to 49 years of age) versus older (50 years and older) patients with asthma. A retrospective analysis of five randomized, double-blind, double-dummy studies 4 to 12 weeks in duration of 1,742 patients <50 years of age and 243 patients aged 50 years or older. Interventions were inhaled fluticasone propionate (FP) 88 microg, oral Z 20 mg, or placebo twice daily. Treatment with FP resulted in significantly greater improvements than Z in all efficacy measurements (except for nighttime awakenings) regardless of age. In older patients, treatment with FP significantly increased pulmonary function compared with Z: FEV (FP= +0.19 L; placebo = -0.34 L; Z = -0.06 L); AM peak expiratory flow rate [PEFR] (FP = +25 L/minute; placebo = -18 L/minute; Z = +4 L/minute); PM PEFR (FP = +24 L/minute; placebo = -24 L/minute; Z = +5 L/minute; P < or = 0.023; for all comparisons). Compared with Z, treatment with FP in older patients also resulted in significantly greater increases in the percentage of symptom-free days (25% vs 13%) and rescue-free days (35% vs 17%); and significantly greater reductions in albuterol use (-1.6 vs -0.3 puffs/day) and the percentage of patients with exacerbations (2.7% vs 14.3%; P < or = 0.031). Regardless of age, treatment with FP in patients with asthma significantly improved pulmonary function and overall asthma control. In contrast, treatment with Z in older patients with asthma resulted in small improvements in asthma symptoms, whereas lung function improved minimally or not at all, and exacerbations increased. These data suggest that FP effectively controls inflammation in older patients, whereas Z may mask inflammation and may not provide the level of bronchodilatory or anti-inflammatory activity needed for effective asthma control in older patients.

Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: An analysis of asthma exacerbations

Background: Adding salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP. Objective: We sought to compare the rates and characteristics of asthma exacerbations in patients after adding salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP. Methods: In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88μg twice daily FP randomly received either 42 μg of salmeterol and 88 μg of FP or an increased dose of FP (220μg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation. Results: The addition of salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP (P = .017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation (P < .05). In both groups clinical indicators of worsening asthma showed parallel changes before asthma exacerbation, and greater improvements were observed after exacerbation with salmeterol compared with higher dose FP. Conclusion: Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups. (J Allergy Clin Immunol 2001;107:783-9.)

Onset of therapeutic effect of fluticasone propionate aqueous nasal spray.

The effectiveness of fluticasone propionate (FP) aqueous nasal spray in the treatment of rhinitis has been demonstrated in multiple controlled clinical studies. The onset of therapeutic effect of FP in these clinical trials appears to occur within 12 hours after administration of the initial dose. This article presents an analysis from previous clinical trials that examined the efficacy of intranasal FP in patients with rhinitis to ascertain whether the time to onset of the therapeutic effect of this medication could be determined. Completed randomized, double-blind, placebo-controlled studies with FP were evaluated to determine whether onset of effect could be evaluated based on the study designs. A study was deemed acceptable for evaluation of onset of effect if at least one evaluation of the intensity of nasal symptoms was completed within 12 hours after the initial dose of study medication and daily evaluations were made thereafter. Adult patients were included in the onset analysis if they received an initial FP dose of 200 microg. Pediatric patients who received an initial FP dose of 100 microg were also included. Onset of effect was evaluated by 1) examining the timepoints at which statistically significant differences were observed between FP and placebo in mean change from baseline for total nasal symptom score (TNSS); and by 2) using a binary probability model of success/failure to determine statistically significant differences from placebo. Twenty-two studies met the criteria to evaluate onset of therapeutic effect; 3,605 patients with rhinitis received FP and 2,271 patients received placebo. This database represents the largest compilation of data ever assembled to determine the onset of therapeutic effect of a corticosteroid nasal spray. Two studies used a "park design" to examine onset of effect; statistically significant differences in TNSS favoring FP were achieved at hours 2 to 4 and at hour 12, respectively. Using a binary probability model of success/failure for analysis of TNSS in the remaining 20 studies not specifically designed to evaluate onset of effect, numerically greater improvements in TNSS for FP compared with placebo were found in 19 of the 20 studies within 12 hours of the administration of the first dose (P < .001). Pairwise comparisons showed statistically significant improvement for TNSS within 12 hours postdose in five of the studies for FP compared with placebo and in none for placebo compared with FP. Onset of therapeutic effect occurs within 12 hours, and as early as 2 to 4 hours in some patients, after administration of the first dose of FP aqueous nasal spray.

Improvement in Health Care Utilization and Pulmonary Function with Fluticasone Propionate in Patients with Steroid-Dependent Asthma at a National Asthma Referral Center

The impact of switching from other inhaled corticosteroids to fluticasone propionate was studied in patients with severe oral-steroid-dependent asthma over a 1-year period. In this open-label prospective study, patients on maintenance doses of oral and inhaled steroids were referred to a national asthma treatment center and were switched from their previous inhaled corticosteroid to fluticasone propionate 880 μg BID. Compared with data collected from the year prior to enrollment, treatment with fluticasone propionate resulted in significant improvements in pulmonary function, oral steroid requirements, and health resource utilization. In addition, five patients were completely weaned off oral steroids.

Inhaled fluticasone propionate. A pharmacoeconomic review of its use in the management of asthma.

Contemporary asthma management guidelines list inhaled corticosteroids as the preferred controller medication for patients with persistent asthma. Despite the availability of explicit guidelines, there is evidence that these agents are underused and that guidelines are not always adhered to. Fluticasone propionate is one of several inhaled corticosteroids used for the treatment of asthma. Like other agents of its class, its efficacy is backed by extensive clinical data. More recently, the quality of life of recipients of fluticasone propionate and its relative cost effectiveness have been investigated. A series of comparative analyses show that inhaled fluticasone propionate is more cost effective than oral zafirlukast and triamcinolone acetonide and slightly more cost effective than flunisolide in adult patients with asthma. Analyses used cost per symptom-free day and/or cost per successfully treated patient as outcome measures and were generally conducted from the perspective of the third-party payer. When administered at a microgram dose of half or less than budesonide (as is therapeutically appropriate), the cost effectiveness of fluticasone propionate was similar to or better than that of budesonide. In children, fluticasone propionate was more cost effective per treatment success compared with inhaled sodium cromoglycate. Quality-of-life assessments in patients with mild to moderate disease show that inhaled fluticasone propionate achieved improvements which were deemed to be clinically meaningful in patients with mild to moderate asthma; these changes were significantly greater than those achieved with oral zafirlukast, inhaled triamcinolone acetonide or placebo. Greater improvements were evident with inhaled fluticasone propionate in patients with severe disease. In addition to the considerable body of clinical evidence supporting the use of inhaled fluticasone propionate in patients with asthma, accumulating short term cost-effectiveness data also suggest that this agent can be administered for a similar or lower cost per outcome than other inhaled corticosteroids or oral zafirlukast. Importantly, the clinical benefits offered by fluticasone propionate in patients with persistent asthma are accompanied by clinically significant improvements in quality of life.

Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study

Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity. We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75% and stable on high-dose inhaled corticosteroids). Patients received one 1000 microg intravenous dose or 1000 microg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat. After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL(-1) h(-1) [2262-3949], -62% difference [45-72]; p<0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p<0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70]; p=0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate. Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.