Flonase
Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma.

O'Connor RD, Nelson H, Borker R, Emmett A, Jhingran P, Rickard K, Dorinsky P.

Department of Quality Management, Sharp Rees-Stealy Medical Group, San Diego, California 92101, USA. richard.oconnor sharp.com

BACKGROUND: Asthma is a chronic disease, the two main components of which are inflammation and bronchoconstriction. Fluticasone propionate (FP) and salmeterol, a strategy that treats both main components of asthma, has been recently compared with FP plus montelukast in a randomised clinical trial. The present study reports economic evaluation of these two strategies. OBJECTIVE: To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50 microg twice daily administered via a single Diskus inhaler device versus treatment with FP 100 microg twice daily via a Diskus inhaler plus oral montelukast 10mg once daily. STUDY DESIGN: A cost-effectiveness analysis was performed by applying cost unit data to resource utilisation data collected prospectively during a US randomised, double-blind, 12-week trial of FP/salmeterol (n = 222) versus FP + montelukast (n = 225). Patients were > or =15 years of age and were symptomatic despite inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS: Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days. Direct costs included those related to study drugs, emergency room department visits, unscheduled physician visits, treatment of drug-related adverse events (oral candidiasis), and rescue medication (salbutamol [albuterol]). The study assumed a US third-party payer's perspective with costs in 2001 US dollars. RESULTS: Treatment with FP/salmeterol resulted in a significantly higher proportion (p < 0.001) of patients who achieved a > or =12% increase in FEV(1) than treatment with FP + montelukast (54% [95% CI 47%, 61%] vs 32% [95% CI 26%, 38%]). Lower daily costs and greater efficacy of FP/salmeterol resulted in a cost-effectiveness ratio of US6.77 dollars (95% CI US5.99 dollars, US7.66 dollars) per successfully treated patient in the FP/salmeterol group compared with US14.59 dollars (95% CI US12.12 dollars, US17.77 dollars) for FP + montelukast. In addition, FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast (31% [95% CI 26%, 35%] vs 27% [95% CI 23%, 32%]), but at a significantly lower daily per-patient cost (US3.64 dollars [95% CI US3.60, US3.68 dollars] vs US4.64 dollars [95% CI US4.56 dollars, US4.73 dollars]). Sensitivity analyses demonstrated the stability of the results over a range of assumptions. CONCLUSION: From a US third-party payer's perspective, these findings suggest that treating the two main components of asthma (inflammation and bronchoconstriction) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma. The results were found to be robust over a range of assumptions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15294013&dopt=Abstract fluticasone Flonase



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Side-effects of fluticasone in asthmatic children: no effects after dose reduction.

Visser MJ, van der Veer E, Postma DS, Arends LR, de Vries TW, Brand PL, Duiverman EJ.

Dept of Pulmonology, University Hospital Groningen, P.O.Box 30,001, 9700 RB, Groningen, the Netherlands. M.Visser int.azg.nl

To assess long-term effects and side-effects of fluticasone propionate (FP), a 2-yr study was performed, comparing a step-down dose approach (1,000 microg.day(-1), with reductions every 2 months to 500, 200 and 100 microg.day(-1) for the remainder of the study) versus a constant dose (200 microg.day(-1)). In 55 children with chronic persistent asthma, aged 6-10 yrs, airways hyperresponsiveness (AHR) and systemic side-effects (height, bone parameters and adrenal cortical function) were assessed at predetermined intervals in a double-blind prospective 2-yr study. AHR improved after 4 months treatment with 1,000 microg.day(-1) FP followed by 500 microg.day(-1), without significant differences during long-term treatment between the two approaches. Dose-dependent reduction of growth velocity, adrenal cortical function and biochemical bone turnover was found during therapy with 1,000 and 500 microg.day(-1) FP when compared with 200 microg.day(-1). In conclusion, doses of 1,000 and 500 microg.day(-1) fluticasone propionate are associated with marked reductions of growth velocity, bone turnover and adrenal cortical function. However, conventional doses (< or =200 microg.day(-1) fluticasone propionate) appear to be safe in the long-term management of childhood asthma. From a safety point of view, high doses of fluticasone propionate should only be prescribed in exceptions, e.g. in persistent severe asthma.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15358701&dopt=Abstract fluticasone Flonase



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The effect of fluticasone on the airway inflammatory response to organic dust.

Ek A, Palmberg L, Larsson K.

Lung and Allergy Research, Division of Physiology, Institute of Environmental Medicine, Karolinska Institutet, PO Box 287, SE-171 77, Stockholm, Sweden. alexandra.ek imm.ki.se

Exposure to organic dust in a swine house causes acute airway inflammation and increased bronchial responsiveness to methacholine in healthy subjects. The aim of this study was to investigate whether an inhaled glucocorticoid, fluticasone propionate, alters the acute airway responses induced by exposure in a swine barn. In 15 healthy subjects, analysis of nasal lavage fluids, serum samples and bronchial methacholine responsiveness were performed before and after exposure to organic dust in a swine house for 3 h. Seven subjects received fluticasone propionate (500 microg b.i.d. by inhalation and 100 microg intranasally once daily) and eight subjects received placebo during the 2 weeks prior to exposure. Post-exposure plasma interleukin (IL)-6 levels and body temperature were significantly lower in the fluticasone group than in the placebo group. Intranasally administered fluticasone propionate significantly attenuated the plasma protein (assessed as albumin concentrations) leakage and IL-8 and tumour necrosis factor-alpha response induced by exposure. Fluticasone propionate inhalation exerted no influence on the increased bronchial responsiveness to methacholine induced by exposure. In conclusion, glucocorticoid treatment attenuated the inflammatory response to inhaled organic dust without influencing the increased bronchial responsiveness to methacholine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15459137&dopt=Abstract fluticasone Flonase



Flonase
Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps.

Burgel PR, Cardell LO, Ueki IF, Nadel JA.

Cardiovascular Research Institute, Box 0130, University of California San Francisco, San Francisco, CA 94 143-0130, USA.

Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 microg.day(-1)). Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF-alpha expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15459138&dopt=Abstract fluticasone Flonase



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Biological availability of inhaled fluticasone propionate in horses.

Laan TT, Westermann CM, Dijkstra AV, van Nieuwstadt RA, Fink-Gremmels J.

Faculty of Veterinary Medicine, Department of Equine Sciences, Internal Medicine Section, Utrecht University, PO Box 80152, 3508 TD, Utrecht, The Netherlands.

Healthy horses received aerosolised, intranasal or oral doses of 3 mg of fluticasone propionate evenly divided over morning and evening treatments for seven days. The bioavailability of the drug was determined in terms of the suppression of the endogenous cortisol concentrations in the horses during the period of treatment. The horses which received the aerosolised drug had significantly lower concentrations of endogenous cortisol on days 5 and 8 than the horses which received aerosolised placebo. The horses which received nasal and oral doses of fluticasone propionate showed no significant changes in their endogenous cortisol concentrations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15493604&dopt=Abstract fluticasone Flonase