Flonase
Fluticasone is associated with lower asthma-related costs than leukotriene modifiers in a real-world analysis.

Armstrong EP, Malone DC.

College of Pharmacy, University of Arizona, Tucson 85721, USA.

STUDY OBJECTIVE: To compare the impact of fluticasone propionate versus three leukotriene modifiers-montelukast, zafirlukast, and zileuton-on the cost of asthma within a managed care organization. DESIGN: Retrospective quasi-experimental comparison. SETTING: Managed care organization with approximately 350,000 enrollees. PATIENTS: Three hundred forty-seven patients with asthma who received at least two prescriptions for either fluticasone or a leukotriene modifier. Patients receiving both fluticasone and a leukotriene modifier were excluded. MEASUREMENTS AND MAIN RESULTS: Multivariate analysis was used to compare total asthma-related costs between treatment groups. A significant difference in total asthma-related costs was found between patients receiving fluticasone (adjusted mean cost $511) compared with those receiving a leukotriene modifier ($1,092; p=0.0001). Other significant predictors of postindex asthma-related costs were pre-index asthma-related costs, a severity adjustment score, and the diagnosis of chronic obstructive pulmonary disease. Patients taking a leukotriene modifier obtained more short-acting beta-agonists than patients receiving fluticasone (6.49 +/- 4.05 vs 4.30 +/- 3.41, p < 0.0001). A survival analysis of time to receive any additional controller therapy revealed that patients receiving fluticasone were significantly less likely to receive another controller than were those receiving a leukotriene modifier (p=0.0014). CONCLUSION: These results suggest that fluticasone is associated with lower asthma-related costs than leukotriene modifiers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12222547&dopt=Abstract fluticasone Flonase



Flonase
Molecular mechanisms of repression of eotaxin expression with fluticasone propionate in airway epithelial cells.

Matsukura S, Kokubu F, Kurokawa M, Kawaguchi M, Kuga H, Ieki K, Odaka M, Suzuki S, Watanabe S, Takeuchi H, Schleimer RP, Schindler U, Adachi M.

First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan. smatsuku med.showa-u.ac.jp

BACKGROUND: Glucocorticoids are known to repress the expression of CC chemokine eotaxin in airway epithelial cells. We focused our study on the molecular mechanisms of the glucocorticoid, fluticasone, in the inhibition of the expression of the eotaxin gene in the cells. METHODS: The airway epithelial cell line, BEAS-2B, was stably transfected with signal transducers and activators of transcription 6 (STAT6)-expressing vector and used in the following experiments to clarify the function of STAT6. Levels of eotaxin mRNA and protein expression were determined with RT-PCR and ELISA. Mechanisms of transcriptional regulation were assessed by the electrophoretic mobility shift assay and dual luciferase assay using eotaxin promoter-luciferase reporter plasmids. RESULTS: Fluticasone significantly inhibited the induction of eotaxin protein stimulated with TNF-alpha and IL-4 in the cells. Fluticasone also repressed the induction of eotaxin mRNA with these stimuli. It partially inhibited the activity of eotaxin promoter; however, it did not inhibit the nuclear translocation and binding of transcription factors, nuclear factor-kappa B (NF-kappaB) or STAT6, to the DNA derived from the proximal promoter region of the eotaxin gene. Moreover, the inhibitory effect was also conserved in the experiments using the reporter plasmid of which the putative glucocorticoid-responsive element was mutated. CONCLUSIONS: Fluticasone inhibits the expression of eotaxin gene in airway epithelial cells in part through repression of the transcription. However, the mechanisms depend neither on the inhibition of transcription factors' translocation into nuclei nor the function of the putative glucocorticoid-responsive element in the promoter, indicating that other mechanisms would be related to the transcriptional repression of the eotaxin gene in airway epithelial cells. Copyright 2004 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15166478&dopt=Abstract fluticasone Flonase



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Asthma hospitalization risk and costs for patients treated with fluticasone propionate vs montelukast.

Orsini L, Limpa-Amara S, Crown WH, Stanford RH, Kamal K.

Medstat Inc, Cambridge, Massachusetts 02140, USA. lucinda.orsini thomson.com

BACKGROUND: Inhaled corticosteroids have been shown to reduce rates of hospitalization and emergency department use compared with leukotriene receptor antagonists. OBJECTIVE: To examine differences in the probability of asthma-related hospitalizations, probability of switching or augmentin, with another therapy, and costs for patients treated with fluticasone propionate vs montelukast. METHODS: The study involved a 24-month retrospective analysis of patients with claims for asthma treatment (primary diagnosis International Classification of Disease, Ninth Revision code of 493.xx) between January 1, 1997, and June 30, 2000, and at least I outpatient pharmaceutical claim for fluticasone propionate (44 microg) or montelukast (5 or 10 mg). Univariate and multivariate analyses were used to determine the probability of asthma-related hospitalizations and switching or augmenting to another therapy, asthma costs, and total health care costs. Sensitivity analyses were conducted by replicating all of the analyses by age strata (ages 4-17 years and > or = 18 years) and varying lengths of follow-up. RESULTS: Patients receiving fluticasone propionate had a 62% lower risk of experiencing an asthma-related hospitalization within 1 year and a 44% lower risk of switching or augmenting to another asthma controller medication compared with montelukast. Asthma-related health care expenditures for montelukast patients were dollar 339 higher than for fluticasone propionate users (P < .001). Overall health care expenditures (asthma and nonasthma) were also dollar 1,197 higher in the montelukast group. CONCLUSIONS: Compared with montelukast-treated patients, patients treated with low-dose fluticasone propionate had a significantly lower risk of experiencing an asthma-related hospitalization, a lower risk of switching or augmenting with another controller, and significantly lower asthma and total health care costs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15191020&dopt=Abstract fluticasone Flonase



Flonase
Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis.

Noel RJ, Putnam PE, Collins MH, Assa'ad AH, Guajardo JR, Jameson SC, Rothenberg ME.

Department of Pediatrics, Cincinnati Children's Medical Center, Universityof Cincinnati College of Medicine, OH 45229-3039, USA. Rothenberg cchmc.org

BACKGROUND & AIMS: Eosinophilic esophagitis (EE) is a recently recognized clinical disorder that is understood poorly. We aimed to determine the efficacy of swallowed fluticasone propionate on the immunopathologic features associated with EE. METHODS: A retrospective analysis was performed on 20 pediatric patients with EE. Inclusion criteria specified a peak eosinophil density of > or =24 cells per 400x field in the esophagus and treatment with swallowed fluticasone between 2 endoscopic assessments. Histologic specimens were examined for eosinophil and CD8(+) lymphocyte infiltration, papillary lengthening, and proliferation of the basal layer as determined by monoclonal anti-Ki-67 (MIB-1) antibody staining. RESULTS: The mean time interval between endoscopic assessments was 4.8 months. The patients were divided equally between allergic and nonallergic groups based on the results of skin-prick testing. All of the nonallergic patients responded to fluticasone propionate. The endoscopic appearance of the mucosa improved and microscopic evaluation showed markedly reduced eosinophil infiltration, reduced basal layer hyperplasia documented by a reduced number of MIB-1(+) cells, and a reduced number of CD8(+) lymphocytes. However, allergic patients were relatively refractory to therapy; 20% had a partial response, whereas 20% had no detectable improvement. Esophageal eosinophil levels before and after therapy in all patients strongly correlated with the level of epithelial cell proliferation as measured by MIB-1 staining. CONCLUSIONS: Collectively, these results suggest that patients treated with swallowed fluticasone have improved endoscopic, histologic, and immunologic parameters associated with EE. However, patients with identifiable allergies who fail dietary elimination may have a blunted response to treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15224281&dopt=Abstract fluticasone Flonase



Flonase
Fluticasone propionate/salmeterol for the treatment of chronic-obstructive pulmonary disease.

Dransfield MT, Bailey WC.

Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, 215 THT, 1900 University Blvd, Birmingham, AL 35294, USA. mdransfield99 msn.com

Chronic-obstructive pulmonary disease (COPD) is a global public health problem and its impact is increasing. Although only smoking cessation has been shown to alter the natural history of the disease, current treatment guidelines recommend the use of inhaled bronchodilators to decrease symptoms, improve lung function and quality of life and to prevent exacerbations. For a subset of patients with more severe disease, inhaled corticosteroids may also have a role in achieving these goals. Fluticasone propionate/salmeterol (Advair) or Seretide), GlaxoSmithKline) is a combination inhaled steroid and long-acting bronchodilator that is delivered by a dry-powder inhaler and was recently approved for use in COPD in the US. Fluticasone propionate/salmeterol is a potent bronchodilator and also appears to have important effects on the frequency of exacerbations and overall quality of life for some patients with COPD. Issues of patient selection as well as the pharmacology, efficacy and safety of the drug are discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15264996&dopt=Abstract fluticasone Flonase