Use of High-Dose Inhaled Corticosteroids and Risk of Corticosteroid-Related Adverse Events in Asthma Findings From the NORDSTAR Cohort

Background: The link between the use of oral corticosteroids (OCS) and adverse events (AEs) in asthma is well described. In contrast, whether the use of high-dose inhaled corticosteroids (ICS) poses a risk to these is unknown. Objective: To examine the association between ICS exposure and corticosteroid (CS)-related AEs. Methods: We conducted an observational cohort study using nationwide Swedish registry data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration. We included patients with asthma aged ≥18 years between 2009 and 2019 and calculated their current ICS exposure and average daily ICS dose (budesonide equivalent) in follow-up. The association between ICS exposure and CS-related AEs was analyzed using Cox proportional hazards models adjusting for age, sex, and OCS dose. Results: We included 529,203 patients with asthma. Overall, we observed increased hazard ratios (HRs) in those exposed to high-dose (≥800-1599 μg) and very high dose (≥1600 μg) ICS for several AEs, including cardiovascular disease, type 2 diabetes mellitus (T2DM), osteoporosis, and pneumonia compared with those not exposed to ICS. HRs for the current use of high-dose ICS ranged from 1.11 (95% confidence interval [CI]: 1.06-1.16) for T2DM to 1.65 (95% CI: 1.58-1.72) for pneumonia. Likewise, HRs linked to average daily high-dose ICS ranged from 1.16 (95% CI: 1.02-1.33) for pneumonia to 1.70 (95% CI: 1.38-2.08) for osteoporosis. Sensitivity analysis excluding patients using OCS showed that high-dose ICS was still associated with an increased risk of CS-related AEs. Overall, ICS <800 μg per day had no increased risk, except for cataract. Conclusion: High-dose ICS is associated with an increased risk of several CS-related AEs. This highlights the importance of clinicians considering this risk in patients treated with high-dose and very high dose ICS.