Association of stepping-up to high dose inhaled corticosteroids and risk of future asthma exacerbations: data from the US

Abstract

Background: Real-world data on the benefit of high-dose inhaled corticosteroid (ICS) post-exacerbation are limited.

Objective: To investigate whether stepping-up to high-dose inhaled corticosteroid (ICS) post-severe exacerbation reduces future asthma exacerbation risk in a real-world setting.

Methods: This was a retrospective cohort study using the Optum® Clinformatics® database (October 2015-December 2023). Patients with asthma, aged ≥12 years, with ≥1 severe exacerbation and ≥2 ICS maintenance prescriptions in the 12-months pre-, and ≥1 ICS maintenance prescription in the 3-months post-exacerbation were included. Primary and secondary endpoints were annualized asthma exacerbation rate (AAER) and time to first subsequent severe exacerbation, respectively. We compared endpoints between ICS dose-changing patterns in the 3-month pre- and post-first eligible severe exacerbation: 1. low-to-high versus low-to-medium (low-dose cohort); 2. medium-to-high versus medium-to-medium (medium-dose cohort). Comparability of baseline characteristics was ensured by inverse probability of treatment weighting.

Results: 2,324 and 13,467 subjects were included in the low- and medium-dose cohorts, respectively. Stepping-up ICS from low-to-high versus low-to-medium-dose did not reduce AAER (rate ratio (RR): 0.896 [95% CI 0.738, 1.088]) and did not significantly increase time to next exacerbation (hazard ratio (HR): 0.869 [95% CI 0.720, 1.048]). Stepping-up ICS from medium-to-high versus medium-to-medium dose was associated with a significant increase in AAER (RR 1.169 [95% CI 1.023, 1.336]) and increased likelihood of experiencing an exacerbation (HR: 1.161 [95% CI 1.016, 1.325]). A similar pattern was noted when follow-up was restricted to a maximum of 12-months.

Conclusion: Post- severe exacerbation, stepping-up to high-dose ICS was not associated with reduced exacerbation risk in patients with persistent asthma. Other treatment strategies may prove to be better options in these patients.

Keywords: annualized severe asthma exacerbation rate; persistent asthma; real-world evidence; time to exacerbation.