Comparison of Inhaled Corticosteroids: An Update

H William Kelly, PharmD

Disclosures

The Annals of Pharmacotherapy. 2009;43(3):519-527. 

In This Article

Abstract and Introduction

Abstract

Objective: To review the basis for the estimated comparative daily dosages of inhaled corticosteroids for children and adults that are presented in the National Heart, Lung, and Blood Institute's Expert Panel Report 3; in addition, the pharmacodynamic and pharmacokinetic basis for potential clinical differences among inhaled corticosteroids is discussed.
Data Sources: A complete MEDLINE search was conducted of human studies of asthma pharmacotherapy published between January 1, 2001, and March 15, 2006, followed by a PubMed search up until August 2008, using ciclesonide, inhaled corticosteroids, and pharmacokinetics as key words. Product information on each inhaled corticosteroid was also included.
Study Selection and Data Extraction: Comparative clinical trials of inhaled corticosteroids and systematic reviews for efficacy comparisons were evaluated. Extensive literature reviews, meta-analyses, and selected clinical studies that illustrate or represent specific points of view were selected. Pharmacodynamic and pharmacokinetic data extracted from previously published reviews and specific studies were included.
Data Synthesis: Pharmacodynamic characteristics (glucocorticoid receptor binding) and lung delivery determine the relative clinical efficacy and pharmacokinetic properties (oral bioavailability, lung retention, systemic clearance) and determine comparative therapeutic index of the inhaled corticosteroids. Secondary pharmacokinetic differences (intracellular fatty acid esterification, high serum protein binding) that have been posited to improve duration of action and/or therapeutic index are unproven, and current comparative clinical trials do not support the hypotheses that they provide an advantage. Ultrafine particle meter-dose inhalers (MDIs) have not demonstrated superior asthma control or improved safety over older MDIs. All of the inhaled corticosteroids demonstrate efficacy with once-daily dosing, and all are more effective when dosed twice daily.
Conclusions: Current evidence suggests that all of the inhaled corticosteroids have sufficient therapeutic indexes to provide similar efficacy and safety in low to medium doses. Whether or not some of the newer inhaled corticosteroids offer any advantages at higher doses has yet to be determined.

Introduction

Inhaled corticosteroids remain the most effective antiinflammatory therapy for the treatment of persistent asthma. The new US National Institutes of Health, National Asthma Education and Prevention Program's Guidelines for the Diagnosis and Management of Asthma, Expert Panel Report 3 (EPR3) has stated that the efficacy of low- to medium-dose inhaled corticosteroid therapy outweighs any small risks of adverse effects.[1] Thus, inhaled corticosteroids are listed as preferred monotherapy for mild-to-moderate persistent asthma for patients of all ages and as baseline therapy with various adjunctive therapies for more severe or difficult-to-control disease. The EPR3 has updated the relative clinical comparability inhaled corticosteroid dose chart ( Table 1 )[2,3,4,5,6,7] that was first established in the EPR2, published in 1997.[8] The changes in the dose chart were based on the introduction of new entities (eg, mometasone furoate), as well as significant formulation changes of older drugs (eg, beclomethasone dipropionate) and additional data from comparative clinical trials.

In 1998, The Annals published a comprehensive review of the scientific rationale supporting the comparative inhaled corticosteroid dosing chart in EPR2.[9] The present report reviews the data supporting the changes found in the EPR3 dosing chart. In addition, data supporting comparable dosing of ciclesonide, an inhaled corticosteroid recently approved by the Food and Drug Administration (FDA), are included. Therefore, this is not a comprehensive review of every inhaled corticosteroid, but rather, an update. Some of the references in this article are extensive reviews.[9,10,11,12,13,14] This update should provide clinicians with the background necessary to assess characteristics of the inhaled corticosteroid preparations that are likely to produce clinically significant differences between products. For the purposes of this update and the dosing charts, the doses of each inhaled corticosteroid are those approved by the FDA: for metered-dose inhalers (MDIs), the amount of actuated dose that reaches the patient's mouth; for dry-powder inhalers (DPIs), the amount available in the dose chamber of the device following actuation; and for jet nebulization (NEB), the amount placed in the nebulizer.

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