Abstract
Background Long-term oral corticosteroid (OCS) treatment for severe asthma is known to cause significant adverse effects, but knowledge on effects of lower exposures in general asthma populations is limited. We aimed to explore this in a nationwide Danish asthma population.
Methods Users of asthma medication aged 18–45 years were identified in the Danish nationwide registers during 1999–2018 and followed prospectively in an open-cohort design. Incident OCS users were matched 1:4 to nonusers by propensity scores with replacement. Associations between OCS use and incident comorbidities were examined by Cox regression. Mortality rates, causes of death and rates of unscheduled hospital visits were assessed.
Results OCS users (n=30 352) had, compared with nonusers (n=121 408), an increased risk of all outcomes with evident dose–response relationships starting at cumulative doses of ≤500 mg (prednisolone-equivalent). Hazard ratios ranged from 1.24 (95% CI 1.18–1.30) for fractures to 8.53 (95% CI 3.97–18.33) for adrenal insufficiency. Depression/anxiety had the highest incidence rate difference at 4.3 (95% CI 3.6–5.0) per 1000 person-years. Asthma-specific mortality rates were generally low at 0.15 (95% CI 0.11–0.20) and 0.04 (95% CI 0.02–0.06) per 1000 person-years for OCS users and nonusers, respectively. Mortality rates and unscheduled hospital visits increased with increasing OCS exposure.
Conclusion The study findings should be interpreted with their observational nature in mind. However, we found that even at low cumulative exposure, OCS use in asthma management was associated with increased risk of comorbidities, mortality and unscheduled hospital visits. Effective strategies for optimising asthma control and reducing OCS use are pivotal in asthma management.
Abstract
Oral corticosteroid use in asthma treatment is associated with an increase in morbidity and mortality even after low cumulative doses of ≤500 mg (prednisolone-equivalent) and with evidence of dose–response relationships https://bit.ly/3gBSEAB
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.00776-2022
Author contributions: J.R. Davidsen, D.P. Henriksen, H. Madsen and I.R. Skov conceived the study. I.R. Skov and A. Pottegård designed the study. Data were curated by D.P. Henriksen. J.H. Andersen and A. Pottegård performed the formal analyses. J.R. Davidsen, H. Madsen and I.R. Skov acquired the funding. I.R. Skov wrote the original draft. J.R. Davidsen was the main supervisor. All authors reviewed and approved the final version.
Data availability: The confidential healthcare data used in this study are available from the Danish Health and Medicines Authority upon relevant request and a data extraction fee. In accordance with Danish law, individual-level data is not publicly accessible. Secondary end-points from the sensitivity analyses are available upon request.
Conflict of interest: I.R. Skov reports grants paid to her institution from AstraZeneca, Teva, Novartis, the Odd Fellow Lodge of Haderslev Denmark, the Region of Southern Denmark and the University of Southern Denmark; and personal fees for lectures from Roche, outside the submitted work. A. Pottegård reports participation in research projects funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Servier and LEO Pharma, all regulator-mandated phase IV studies, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the submitted work. J.R. Davidsen reports grants and personal fees for advisory board participation and lectures from Roche and Boehringer Ingelheim, and personal fees for lectures from Chiesi, outside the submitted work. H. Madsen, D.P. Henriksen and J.H. Andersen have nothing to disclose.
Support statement: This work was supported by Novartis, Teva, the Region of Southern Denmark and the University of Southern Denmark, as part of a PhD project. The study was conducted and submitted without influence of any sponsors. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received December 1, 2021.
- Accepted January 27, 2022.
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