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Advair: Combination treatment with fluticasone propionate/salmeterol in the treatment of asthma

https://doi.org/10.1067/mai.2001.112939Get rights and content

Abstract

Several classes of medications are available for the treatment of asthma, and often they must be taken concurrently to achieve asthma control. Based on the understanding of asthma as an inflammatory disease, the National Heart Lung and Blood Institute guidelines provide a stepwise approach to pharmacologic therapy. Corticosteroid therapy, principally inhaled corticosteroid (ICS) therapy, is considered the most effective anti-inflammatory treatment. In cases of moderate-to-severe persistent asthma, the addition of a second long-term control medication to ICS therapy is one recommended treatment option. A combination-product inhaler (Advair, Seretide) was developed to treat both the inflammatory and bronchoconstrictive components of asthma by delivering a dose of the ICS, fluticasone propionate, and a dose of the long-acting β2-adrenergic (LABA) bronchodilator, salmeterol. The Advair Diskus is available in 3 strengths of fluticasone propionate (100, 250, and 500 μg) and a fixed dose (50 μg) of salmeterol. Combination treatment with both ICS and LABA provides greater asthma control than increasing the ICS dose alone, while at the same time reducing the frequency and perhaps the severity of exacerbations. Furthermore, salmeterol added to ICS therapy provides superior asthma control compared with the addition of leukotriene modifiers or theophylline. The superior control is likely a consequence of the complementary actions of the drugs when taken together, including the activation of the glucocorticoid receptor by salmeterol. By combining anti-inflammatory treatment with a long-acting β2-agonist in a single inhaler (1 inhalation twice daily), physicians can provide coverage for both the inflammatory and bronchoconstrictive aspects of asthma without introducing any new or unexpected adverse consequences. The most common drug-related adverse events were those known to be attributable to the constituent medications (ICS therapy and/or LABA therapy). Although the benefits of combined ICS plus LABA therapy can be achieved with separate inhalers, the convenience of the combination product may improve patient adherence and may therefore reduce the morbidity of asthma. (J Allergy Clin Immunol 2001;107:397-416.)

Section snippets

Overview

Several classes of medications are used in the treatment of asthma, including glucocorticoids, short-acting and long-acting β-adrenergic (LABA) bronchodilators, leukotriene modifiers, mast cell stabilizers, methylxanthines, and anticholinergics. These medications are often used in combination to optimize asthma control by improving pulmonary function, preventing symptoms, reducing the need for rescue medication, normalizing activity levels, preventing exacerbations, and minimizing the impact of

National heart lung and blood institute guidelines for the treatment of asthma

The National Heart Lung and Blood Institute Expert Panel 2 Guidelines to the Diagnosis and Management of Asthma classify asthma into 4 levels of severity based on symptoms and lung function measures assessed before the initiation of treatment: (1) mild intermittent asthma, (2) mild persistent asthma, (3) moderate persistent asthma, and (4) severe persistent asthma.1 Corresponding to the 4 levels of severity, a 4-step approach to asthma therapy has been defined. The medications used in this step

Importance of ICS therapy in the treatment of asthma

The importance of ICS therapy in the treatment of asthma cannot be overstated. Asthma is a chronic inflammatory disorder of the airways involving multiple cells and cellular elements including mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells.1 The magnitude of the inflammation and the thickening of the subepithelial layer (airway remodeling) are generally correlated with the severity of asthma but have been observed to some degree even in mild intermittent asthma.2, 3

Efficacy of salmeterol

Salmeterol, a potent β2-adrenergic agonist, is the only long-acting bronchodilator currently available in the United States. Salmeterol provides superior bronchodilation in 12-hour serial pulmonary function studies in comparison to placebo33, 34, 35, 36, 37, 38 and albuterol administered every 6 hours.36, 37, 38, 39 Additionally, salmeterol provides significantly greater improvement than albuterol in predose FEV1 and morning PEF while reducing the requirement for rescue albuterol.36, 37, 38, 39

Evidence that LABAs may mask inflammation

Although long-acting inhaled β2-agonists clearly are the most effective bronchodilators to add to ICS therapy, concerns persist that by allowing the use of a lower dose of ICS, the underlying inflammation of asthma will be masked. This has been fueled by a crossover study where 13 patients taking at least 1500 μg/d of ICS for control of asthma were subjected to a steroid taper while receiving either salmeterol or placebo.85 As predicted, while receiving salmeterol, the patients were able to

Scientific rationale: Complementary action of ICS plus LABA

Considerable research effort has been aimed at characterizing the precise mechanisms of asthma and the contributions of various asthma treatments, fueled in part by the observed and otherwise unexplained clinical benefits of combination therapy with ICS and LABAs. The interactions between corticosteroids and β2-agonists in asthma have been excellently reviewed.92 Perhaps the most important finding in this regard has been the demonstration of the positive complementary actions of ICS and LABA

Studies of advair therapy

The clinical and scientific rationale for the combined use of ICS and LABA is well founded and compelling. No other single therapy or combination of other therapies has been shown to provide equal asthma control or to equally prevent the sequelae of uncontrolled asthma, including exacerbations and hospitalizations. Provided there is flexibility to vary the ICS dose, a combination ICS plus LABA product represents an important treatment advance. Furthermore, there is a compelling need for asthma

Conclusion

This article has reviewed the scientific and clinical rationale for and the efficacy and safety of Advair, a new combination inhaler for the treatment of asthma composed of the ICS fluticasone propionate and the long-acting β2-agonist salmeterol. For patients whose symptoms are inadequately controlled on low-dose ICS therapy, combination therapy provides better asthma control than increasing the dose of ICS. Combination treatment also provides superior asthma control than adding a leukotriene

Acknowledgements

The author thanks Amy Schaberg for her assistance with preparation of this manuscript.

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