Discussion
In this 20-year nationwide utilization study, we found an annual OCS use prevalence at 4.8% among young adults with active asthma with a slight increase in the period 1999 to 2018. Interestingly, we found an almost 40% decrease in the prevalence of high-users (i.e. use of ≥5 mg per day), as well as a halving in the annual median cumulative OCS dose among users. We found that OCS use was associated with older age and female sex in line with previous studies (10, 21, 28).
The prevalence of OCS use in our asthma population was somewhat lower than other European studies based on patients in secondary care (21) or on medical record databases (28). A recent Swedish register study restricted to asthma patients diagnosed in secondary care found 1.5% of patients to have a high OCS use (≥5 mg/y) and 22.9% to have a low OCS use (<5 mg/y) within the baseline year (21). These higher prevalences might reflect a population of patients with more severe asthma compared to our broader cohort of asthma patients, not restricted to secondary care. In addition, patients in this study were generally older with a median age of 33 years. The authors confirmed a stable proportion at 15% of asthma patients using OCS over the 10-year study period. A newer European multi-country study conducted on asthma populations from medical record databases in France, Germany, Italy, and the United Kingdom found 14-44% of asthma patients to be OCS users (28). The annual prevalence of high OCS use (defined as ≥5 mg OCS/d in a 90-day window) was stable at approximately 3% in the period 2011-2018. The findings of overall stable OCS user trends during the last decades are supported by a recent systematic review performed on studies published in the period 2000-2017, which concluded that OCS continues to be commonly used and overused in asthma treatment (10). Authors from this review confirmed a dose-response relationship, where the risk of steroid induced adverse effects increased with increased cumulative OCS doses. Hence, interestingly, repeated rescue high-dose courses of OCS may induce a higher risk of adverse effects than low-dose maintenance treatment (9, 10). The dose-response relationship between cumulative OCS exposure and increased risk of adverse effects has been shown to begin at exposures as low as 1 g of OCS, corresponding to 4 lifetime courses of OCS (9, 11). Of note, more than one in five individuals using OCS in our study were exposed to >1 g of OCS.
Other studies have found trends of increased OCS use during the last decades. This includes a French study on national claim data among 18-40-year-old asthma medication users (29) and a study on electronic healthcare records from the United Kingdom (UK) (30). The latter study demonstrated that the proportion of asthma patients in the UK receiving at least 3 courses of OCS per year doubled from 1% to 2% in the period 2006-2017. Less than 20% of these patients were referred for specialist care in contrary to national recommendations. Though similar numbers have not been explored on a Danish asthma population, this indicates an unmet need for specialist care assessment among frequent OCS users.
The differences in the trends of OCS user prevalence between studies might reflect the different OCS-quantification methods, data availability, differences in treatment practice patterns across the countries and asthma populations, access to asthma specialists, as well as differences in reimbursement to medical expenses as OCS is less expensive than inhaled asthma drugs and thereby easier accessible.
Despite an overall minor increase in the annual prevalence of OCS users, we observed an interesting shift in dosage trends towards lower annual OCS doses, which offers some encouragement. The frequency of high-users, i.e. individuals using ≥1825 mg OCS per year, corresponding to ≥5 mg OCS/day, decreased by almost 40% from 0.54% in 1999 to 0.33% in 2018, and the average intake of OCS per year decreased throughout the observation period with a halving of the median dose from 500 mg to 250 mg from 1999 to 2018. This shift in OCS usage trends was supported by the Lorenz curves and Gini coefficients, which show the trends have changed towards a more equal distribution of OCS consumption among the users with fewer ‘heavy users’. Still, a substantial skewness in OCS consumption among OCS users persisted throughout the observation period, where 10% of the heaviest users accounted for almost 50% of all consumed OCS, though with overall decreasing tendencies from 1999-2018.
This change towards lower OCS doses might reflect several improvements in asthma treatment during the last two decades, including the introduction of fixed dose combination inhalers with ICS and β2-agonist in 2000 (31) and the availability of biological treatment (15). The first biological treatment for asthma treatment approved in Europe in 2005 was anti-IgE therapy (Omalizumab), which has since been followed by several other biologic therapies targeting type 2 inflammatory pathways. These treatments have launched a new era in severe asthma treatment and demonstrated the ability to reduce the use of OCS (15).
Besides describing the OCS usage in asthma treatment, this study also investigated baseline characteristics for a general population of Danish young adults with asthma. Women were more frequent, which is common among adults with asthma (5). Concurrent treatment of asthma-related comorbidities such as allergy and chronic rhinosinusitis was common. This was emphasized by the finding that 54% had a previous use of antihistamines and 36% had a use of nasal corticosteroids, as proxies for treatment-requiring allergies and chronic rhinosinusitis, respectively (see Online Supplement Table E2 ). In Denmark, many antihistamines are available as over-the-counter medication, which was not included in our analyses, thereby likely underestimating the actual use. Less common comorbidities were dyspeptic disorders, anxiety or depression, obesity, sleep apnoea and food allergies, though these prevalences might have been underestimated due to the lack of diagnostic information from general practice. The GINA strategy recommends active management of these comorbidities as they may be associated to or contribute to the symptom burden in patients with asthma (5). Furthermore, Danish studies have found associations between having asthma and schizophrenia (26), and severe mental disorders such as schizophrenia and bipolar disorder increase the risk of hospitalization for asthma (25).