Assessing the Effects of Changing Patterns of Inhaled Corticosteroid Dosing and Adherence with Fluticasone Furoate and Budesonide on Asthma Management

Abstract

Introduction: Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies.

Methods: We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios.

Results: A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence.

Conclusion: In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Keywords: Adherence; Asthma; Bronchoprotection; Budesonide; Dosing regimen; Fluticasone furoate; Systemic effects.

Fig. 1

Study flow diagram. BUD budesonide, FF fluticasone furoate, RWD real-world data

Fig. 2

Dosing and adherence simulations by treatment in mild asthma. BUD budesonide, BID twice daily, DD doubling dose, FF fluticasone propionate, FOR formoterol, OD once daily, PRN as needed

Fig. 3

Dosing and adherence simulations by treatment in moderate-to-severe asthma. BUD budesonide, BID twice daily, DD doubling dose, FF fluticasone furoate, FOR formoterol, MART maintenance and reliever therapy, OD once daily, PRN as needed, VI vilanterol

Fig. 4

Model predicted time course of ICS/LABA induced airway bronchoprotection for 28 days dosing in moderate-to-severe asthma. Dosing was regular daily maintenance with FF/VI 200/25 μg OD (left) and BUD/FOR 400/12 μg × 2 BID (middle), and MART with BUD/FOR 200/6 μg × 2 BID + PRN (right) with adherence scenario of 70% (top row) and 30% adherence (bottom row) to the regular daily maintenance component of the three dosing regimens. Horizontal dotted lines indicate thresholds for no treatment-related bronchoprotective effect defined as bronchoprotection less than an AMP PC₂₀ of 16 mg/mL (0.25 DD) and a clinically significant bronchoprotective effect defined as bronchoprotection greater than an AMP PC₂₀ of 54 mg/mL (2.0 DD). BID twice daily, BUD budesonide, DD doubling dose, FF fluticasone furoate, FOR formoterol, OD once daily, MART maintenance and reliever therapy, PRN as needed

Fig. 5

Dosing and adherence simulations by treatment in RWD studies. adh adherence, BUD budesonide, BID twice daily, DD doubling dose, FF fluticasone furoate, FOR formoterol, MART maintenance and reliever therapy, OD once daily, PRN as needed, RWD real-world data, VI vilanterol