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

• DOI: 10.1007/s12325-021-01976-4
• Publication Date: 2021-12-07T05:01:13Z
• Authors: Peter Daley-Yates; Bhumika Aggarwal; Zrinka Lulic; Sourabh Fulmali; Alvaro A. Cruz; Dave Singh
• Keywords: Fluticasone propionate; Fluticasone; Maintenance therapy; Pharmacodynamics; Maintenance dose

This study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma. A pharmacokinetic/pharmacodynamic model was developed validated describing relationship between ICS dose time-course for airway bronchoprotection, [provocative concentration adenosine monophosphate (AMP) causing ≥ 20% decline forced expiratory volume 1 s (FEV1) (AMP PC20)], fluticasone furoate (FF), propionate (FP) budesonide (BUD). For regular maintenance therapy (100% 50% adherence) infrequent or as-needed use (dosing 3–4 times per week), treatment effectiveness expressed as percent time during 28 days when bronchoprotection exceeded either threshold a treatment-related effect PC20 0.25 doubling dose) clinically significant 1.0 dose). value divided by total administered prednisolone equivalents to give therapeutic index (TI). The model-predicted course ICS-induced with daily 100% adherence showed that all at highest recommended doses asthma most 28-day period, mean (90% CI); (96.1–100), 99.9% (8.0–100) (58.2–100) TI values 16.9, 6.6 5.4 FF 100 µg OD, FP 200 BID BUD BID, respectively. simulated poor (50%) therapy, corresponding CI) were; 75.7% (39.4–89.1), 52.3% (0.7–69.2) 51.3% (28.6–58.3) 25.7, 6.9 5.6. infrequent/as needed 77.0% (37.6–87.0), 25.5% (0.0–38.0) 26.2% (14.3–31.5) 26.1, 6.7 5.7. regimen/scenarios, had sustained efficacy favourable followed BUD. At asthma, provide dosed regularly high adherence. With week (infrequent/as needed), longer-acting molecules will more likely protection better versus shorter duration action (FF > BUD). These data highlight benefits using potential risks under-treatment (which may occur ICS/formoterol approach persistent asthma) associated reduced levels bronchoprotection.