New Versus Old: The Impact of Changing Patterns of Inhaled Corticosteroid Prescribing and Dosing Regimens in Asthma Management

Abstract

Inhaled corticosteroid (ICS)-containing therapies are the mainstay of pharmacological management of asthma. They can be administered alone or in combination with a long-acting bronchodilator, depending on asthma severity, and may also be supplemented with short-acting bronchodilators for as-needed rescue medication. Adherence to asthma therapies is generally poor and characterized by underuse of ICS therapies and over-reliance on short-acting bronchodilators, which leads to poor clinical outcomes. This article reviews efficacy versus systemic activity profiles for various dosing regimens of budesonide (BUD) and fluticasone propionate (FP). We performed a structured literature review of BUD and FP regular daily dosing, and BUD/formoterol (FOR) as-needed dosing, to explore the relationship between various dosing patterns of ICS regimens and the risk-benefit profile in terms of the extent of bronchoprotection and cortisol suppression. In addition, we explored how adherence could potentially affect the risk-benefit profile, in patients with mild, moderate, and moderate-to-severe asthma. With a specific focus on BUD or FP-containing treatments, we found that regular daily ICS and ICS/long-acting β₂-agonist (LABA) dosing had a greater degree of bronchoprotection than as-needed BUD/FOR dosing or BUD/FOR maintenance and reliever therapy (MART) dosing, and still maintained low systemic activity. We also found that the benefits of regular daily ICS dosing regimens were diminished when adherence was low (50%); the shorter duration of bronchoprotection observed was similar to that seen with typical as-needed BUD/FOR usage. These findings have implications for aiding clinicians with selecting the most suitable treatment option for asthma management, and subsequent implications for the advice clinicians give their patients.

Keywords: As-needed dosing; Asthma; Bronchoprotection; Budesonide; Fluticasone propionate; Inhaled corticosteroid; Regular maintenance dosing; Risk benefit; Systemic effects.

Fig. 1

Inclusion/exclusion criteria for literature search. GINA Global Initiative for Asthma, RCT randomized controlled trial, RWD real-world data

Fig. 2

Study flow diagram. ^aThese publications were included even if they did not meet all selection criteria (some publications were already included in the PubMed database search), and were generally cited within review articles identified in the literature search; ^bIncluded 17/34 key publications; ^cKey publications, no other reviews were included; ^dExcluded from initial search because title did not contain details on dosing regimen (n = 2) or the study was a 3-year RWD extension of an RCT already included in literature review (n = 1). ^eOne study [41] did not specify asthma severity but was used for supplementary information for AHEAD [40] and COMPASS [43], two studies that used MART in moderate asthma. FP fluticasone propionate, MART maintenance and reliever therapy, QD once-daily, RCT randomized controlled trial, RWD real-world data

Fig. 3

Comparison of airway efficacy to systemic activity for BUD/FOR as-needed and regular ICS dosing regimens in mild asthma [–11]. AEF airway efficacy, BID twice daily, BUD budesonide, DD doubling dose, FOR formoterol, FP fluticasone propionate, ICS inhaled corticosteroid, PRN as needed, SA systemic activity

Fig. 4

Comparison of airway efficacy to systemic activity for BUD/FOR MART and regular ICS/LABA dosing regimens in (A) moderate asthma and (B) moderate-to-severe asthma [21, 25, 29, 30, 34, 40, 43]. ^aTwo inhalations BID. AEF airway efficacy, BID twice daily, BUD budesonide, DD doubling dose, FOR formoterol, FP fluticasone propionate, ICS inhaled corticosteroid, LABA long-acting bronchodilator, MART maintenance and reliever therapy, QD once daily, PRN as needed, SA systemic activity, SAL salmeterol