Inhaled Fluticasone Propionate

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.

Asthma affects over 100 million people worldwide and is increasing in prevalence, particularly in children and young adults. Asthma-related mortality has either increased or stabilised, depending on geographical location.

It is estimated that approximately 70 to 80% of patients have clinically mild or seasonal asthma. 15 to 20% have moderate persistent asthma and the remainder have severe persistent asthma.

In the last decade, international guidelines for the management of asthma have been developed and disseminated. Inhaled corticosteroids are recommended as the controller therapy of choice for adult patients with persistent asthma.

The cost of asthma to individuals and society is immense. In 1990, direct medical expenses in the US were $US3.6 billion and indirect costs accounted for an additional $US2.6 billion. Of the amount spent on medical care treatments, approximately 56% was for inpatient hospital stays, outpatient hospital visits and emergency department care. Physician-related services accounted for 14% and asthma medication accounted for 30% of direct costs.

The bulk of asthma-related cost is due to poorly controlled disease. Disease severity is also an important determinant of cost; patients with severe disease (up to 15% of patients with asthma) account for 50 to 80% of hospital admissions and resource use.

Symptoms of asthma can impair the quality of life of a patient. Troublesome symptoms identified by patients generally include shortness of breath, chest tightness, wheezing and coughing, which in turn can affect daily activities. Quality-of-life scales show that the burden of asthma is amplified with increasing disease severity.

The impact of asthma on the quality of life of children is difficult to assess, and issues for children differ from those in adult patients. Children with asthma can find integration with peers difficult because of their inability to participate in activities, sports and social outings. The lives of parents can also be affected.

In patients with mild to moderate asthma, inhaled fluticasone propionate (≤500 μ/day) is significantly more effective than oral zafirlukast (20mg twice daily), inhaled nedocromil (4mg 4 times daily) and oral theophylline in improving lung function.

In comparative trials, fluticasone propionate produced equivalent or greater improvements in lung function compared with budesonide or beclomethasone dipropionate when administered at half of the microgram dose of these agents in patients with asthma.

Fluticasone propionate 250μg twice daily had similar efficacy to flunisolide 500μg twice daily and significantly better efficacy than triamcinolone acetonide 200μg 4 times daily in comparative studies in patients with mild to moderate and moderate to severe asthma, respectively.

The efficacy profile of fluticasone propionate in children is similar to that in adults. In a comparative trial, fluticasone propionate was significantly more effective at improving lung function measures than inhaled sodium cromoglycate (20mg 4 times daily). At half the microgram dose of budesonide or beclomethasone dipropionate, fluticasone propionate was significantly better than budesonide and produced similar results to beclomethasone dipropionate.

The most common adverse events occurring with inhaled fluticasone propionate are upper respiratory infections, headache, pharyngitis, nasal congestion, oral candidiasis, rhinitis and dysphonia; the incidence of these events does not differ markedly from that in patients receiving placebo, budesonide or beclomethasone dipropionate in comparative trials.Aswith all inhaled corticosteroids, adverse systemic events are possible in a small proportion of patients receiving prolonged therapy at high dosages.

Treatment with inhaled fluticasone propionate over the normal therapeutic range (dosages of ≤1000 and ≤200 μ/day for adults and children, respectively) for up to 2 years does not cause clinically relevant suppression of the hypothalamic- pituitary-adrenal axis. At the same dosages, fluticasone propionate does not appear to reduce bone mineral density in adults or reduce growth in children.

The introduction of inhaled fluticasone propionate to centres in the US and UK was associated with an overall mean decrease or small increase (−22 to +2%) in the management costs of asthma compared with costs before the its introduction. These changes were significantly smaller (p < 0.05) than those observed with leucotriene receptor antagonists (montelukast or zafirlukast) and other inhaled corticosteroids (triamcinolone acetonide or beclomethasone dipropionate) in 4 US studies. Resource use and direct medical costs were considered in these analyses.

A series of comparative cost-effectiveness analyses showed that inhaled fluticasone propionate was more cost effective than oral zafirlukast and triamcinolone acetonide and slightly more cost effective than flunisolide in adult patients with asthma. All analyses used cost per symptom-free day and/or cost per successfully treated patient as outcome measures, although the definition of treatment success varied markedly between studies. Where stated, analyses were conducted from the perspective of the third-party payer and considered direct costs.

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. Fluticasone propionate was consistently more cost effective than budesonide regardless of disease severity.

In children with asthma, fluticasone propionate was associated with a cost-effectiveness advantage of greater than 2: 1 compared with inhaled sodium cromoglycate.

Patient quality of life associated with the use of inhaled fluticasone propionate has been assessed in several clinical trials, many of which used the disease-specific Asthma Quality of Life Questionnaire (AQLQ). For this instrument, a change in score of 0.5 from baseline has been identified as the minimum important (or clinically meaningful) difference.

In a combined analysis of 6 controlled clinical trials in patients with mild to moderate disease, inhaled fluticasone propionate achieved an improvement of approximately 0.6 points in overall AQLQ score compared with a change of 0.1 with zafirlukast. In another analysis, the change in overall AQLQ score with fluticasone propionate was 0.4, which was significantly better than that achieved with triamcinolone acetonide (0.0) or placebo (−0.5).

In patients with severe disease, inhaled fluticasone propionate improved mean overall AQLQ scores by 0.84 and 1.29 at dosages of 1000 and 2000 μ/day, respectively; these changes were significantly better than that observed with placebo (−0.38). Compared with beclomethasone dipropionate or budesonide, fluticasone propionate achieved a significant improvement in overall AQLQ score of 0.66 versus 0.15.

In children with mild to moderate asthma (4 to 12 years of age), inhaled fluticasone propionate significantly improved mean scores of 3 different quality-of-life questionnaires assessed by proxy (Functional Status IIR, the Sleep Scale- Children and one dimension of the Quality of Life of Parents of Asthmatic Children) compared with placebo. Although the results were statistically significant, the absolute changes were small. In the absence of a defined minimum clinically important difference for each instrument, it is difficult to interpret the clinical relevance of these results.