Pharmacology Versus Convenience: A Benefit/Risk Analysis of Regular Maintenance Versus Infrequent or As-Needed Inhaled Corticosteroid Use in Mild Asthma.

Abstract

INTRODUCTION:

This study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma.

METHODS:

A pharmacokinetic/pharmacodynamic model was developed and validated describing the relationship between ICS dose and time-course for airway bronchoprotection, [provocative concentration of adenosine monophosphate (AMP) causing ≥ 20% decline in forced expiratory volume in 1 s (FEV1) (AMP PC20)], for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD). For regular ICS maintenance therapy (100% and 50% adherence) and infrequent or as-needed use (dosing 3-4 times per week), treatment effectiveness was expressed as percent time during 28 days when bronchoprotection exceeded either the threshold for a treatment-related bronchoprotective effect (AMP PC20 ≥ 0.25 doubling dose) or the threshold for a clinically significant bronchoprotective effect (AMP PC20 ≥ 1.0 doubling dose). This value was divided by the total ICS dose administered expressed in prednisolone equivalents to give a therapeutic index (TI).

RESULTS:

The model-predicted time course of ICS-induced bronchoprotection with regular daily maintenance dosing and 100% adherence showed that all ICS at the highest recommended doses for mild asthma exceeded the threshold for clinically significant bronchoprotective effect for all or most of the 28-day dosing period, mean (90% CI); 100% (96.1-100), 99.9% (8.0-100) and 100% (58.2-100) with TI values of 16.9, 6.6 and 5.4 for FF 100 µg OD, FP 200 µg BID and BUD 200 µg BID, respectively. For simulated poor adherence (50%) to regular daily maintenance therapy, corresponding mean (90% CI) values were; 75.7% (39.4-89.1), 52.3% (0.7-69.2) and 51.3% (28.6-58.3) with TI values of 25.7, 6.9 and 5.6. For simulated infrequent/as needed use the corresponding values were; 77.0% (37.6-87.0), 25.5% (0.0-38.0) and 26.2% (14.3-31.5) with TI values of 26.1, 6.7 and 5.7. For all regimen/scenarios, FF had the most sustained efficacy and favourable TI followed by FP and BUD.

CONCLUSIONS:

At doses recommended for mild asthma, all ICS regimens provide sustained bronchoprotective efficacy when dosed regularly with high adherence. With poor adherence or use 3-4 times per week (infrequent/as needed), longer-acting ICS molecules will more likely provide sustained protection and a better TI versus shorter duration of action molecules (FF > FP ≥ BUD). These data highlight the benefits of using ICS as regular daily maintenance dosing in mild asthma and the potential risks of under-treatment with ICS (which may occur with ICS/formoterol as-needed approach in mild persistent asthma) associated with reduced levels of bronchoprotection.

• Authors: Peter Daley-Yates, Bhumika Aggarwal, Zrinka Lulic, Sourabh Fulmali, Alvaro A Cruz, Dave Singh
• Journal: Advances in therapy (Adv Ther) Vol. 39 Issue 1 Pg. 706-726 (01 2022) ISSN: 1865-8652 [Electronic] United States
• PMID: 34873657 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Adrenal Cortex Hormones
• Androstadienes
• Anti-Asthmatic Agents
• Drug Combinations
• Fluticasone

Topics

• Administration, Inhalation
• Adrenal Cortex Hormones (therapeutic use)
• Androstadienes (therapeutic use)
• Anti-Asthmatic Agents (therapeutic use)
• Asthma (drug therapy)
• Drug Combinations
• Fluticasone (therapeutic use)
• Humans
• Risk Assessment