Association of Stepping Up to High-Dose Inhaled Corticosteroids and Risk of Future Asthma Exacerbations: Data From the United States

Background: Real-world data on the benefit of high-dose inhaled corticosteroid (ICS) after exacerbation are limited. Objective: To investigate whether stepping up to high-dose ICS after 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 to December 2023). Patients with asthma, aged ≥12 years, with ≥1 severe exacerbation and ≥2 ICS maintenance prescriptions in the 12 months before and ≥1 ICS maintenance prescription in the 3 months after exacerbation were included. Primary and secondary end points were annualized asthma exacerbation rate (AAER) and time to first subsequent severe exacerbation, respectively. We compared the end points between ICS dose-changing patterns in the 3 months before and after first eligible severe exacerbation: (1) low-to-high versus low-to-medium (low-dose cohort) and (2) medium-to-high versus medium-to-medium (medium-dose cohort). Comparability of baseline characteristics was ensured by inverse probability of treatment weighting. Results: A total of 2324 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% confidence interval (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. Conclusions: After 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.