Prevalence of oral corticosteroid use in the German severe asthma population

Discussion

The present study describes the prevalence of asthma in a representative sample from Germany in terms of age and sex, based on SHI routine data. In this sample of adult patients, the asthma prevalence was 7.3%, which is greater than the estimated 5% reported earlier for the overall German population [17]. Of these asthma patients, 8.7% (0.6% absolute) were treated with HD-ICS/LABAs, defined as steps 4/5 according to the GINA criteria [2], consistent with the reported global prevalence of severe asthma of approximately 5–10% of asthma patients [5, 6]. The frequency of patients on HD-ICS/LABAs who required additional OCSs was 2.9% and is comparable to data from the Netherlands that reported a frequency of 3.6% [5]. A possible explanation for the slightly lower prevalence in the present analysis may be a result of exclusive consideration of prescription data; since additional clinical data on current asthma control were not available within SHI, both prescription data and clinical data were considered in the analysis of the Dutch population. In 2015 82.9% of the asthma patients in Germany who had maintenance therapy with HD-ICS/LABAs and needed OCSs at least once, received an intensive therapy with OCSs (either frequent short-term or long-term).

The present analysis demonstrates that, in Germany, OCS therapy is an established and frequently applied treatment option for patients with severe, inadequately controlled asthma. While OCSs may be appropriate and a relatively well-tolerated treatment option for acute exacerbations (i.e. OCS bursts at usually high dosages), these data revealed the frequent use of comparatively high dosages during long-term treatment. Patients who received long-term OCS for more than 180 days in a year received an average of 9.1 mg of prednisolone equivalent per day and were substantially above the national and international guideline recommendations that recommend OCS maintenance therapy in step 5 of the therapy regimen only as secondary and intermittent treatment and at dosages of less than 7.5 mg of prednisolone equivalent per day [2, 18, 19]. In addition, OCSs at a rather high dosage (3.3 mg·day⁻¹) was also administered widely (i.e. for all patients with therapy duration >20 days), which is of concern, as frequent OCS-associated adverse effects have been reported with usage from a daily dosage >2.5 mg [20].

Comorbidities in patients with asthma are frequent, increase with the duration and intensity of OCS therapy, and mainly affect certain organ systems. Here, a distinction must be made between frequently accompanying but not causally linked comorbidities and direct/indirect, OCS-induced adverse effects [21]. Comparable frequencies were reported from the analysis of a healthcare database in the United Kingdom, which described at least one potential steroid-induced comorbidity in 93% and more than three in 53% of all patients with severe asthma [9]. The dosages used, amounting to 1960 mg per year, were essentially comparable with the data from our analysis (1826 mg), as was the profile of most frequently observed comorbidities, despite slightly different definitions. A further analysis of prescription data from the United States described an increase in comorbidities in asthmatic patients with intensive OCS therapy (at least 30 days with OCS intake per year) compared with asthma patients without OCS therapy, resulting in increased frequencies of osteoporosis, cataract/glaucoma, diabetes mellitus and hypertension. The frequencies of the comorbidities associated with OCS maintenance therapy described in the present analysis are comparable with the United States data clustered into categories of skeletal muscle, connective tissue and bone diseases, ocular disorders, metabolic and nutritional disorders, and cardiac conditions [10]. Dosage dependencies have been described by Amelink [7] both for psychiatric conditions and for diabetes. The increase in comorbidities we observed for patients receiving short-term OCS therapy also confirms data analysed from earlier studies reporting an increase in OCS-associated comorbidities with short-term OCS use for less than 30 days [12] and relatively low-dosage OCS maintenance therapy below the so-called Cushing threshold [9].

Asthma, and especially severe asthma, are a significant burden on payers. The cost analyses available for Germany, however, are predominantly outdated and do not relate to the current state of knowledge, modern treatment strategies, and cost and reimbursement structure [22, 23]. In addition, they rarely differentiate by asthma severity, and they take different perspectives (e.g. SHI, pension insurance), hampering comparability. For example, the direct total costs of patients with atopic asthma associated with seasonal allergic rhinitis are estimated by Schramm et al. [24] to be €569 per adult in mild asthma and up to €2048 for severe asthma. If the indirect costs are included, the amount increases to up to €9286 per year and patient. Kirsch et al. [23] determined total asthma costs per case and year of between €445 and €2543 by means of a systematic literature search.

We found that mean annual direct costs per patient and year increased from €5096, for patients with HD-ICS/LABAs and a one-time short-term OCS prescription, to €8208 for the group of patients with multiple OCS bursts of therapy or maintenance-therapy OCSs. Long-term treatment with OCSs for more than 180 days per year more than doubled the cost compared with the patient group with a one-time, short-term OCS prescription (€5096 versus €11 253). The latter amount roughly corresponds to the costs for severe asthma of €11 703 per patient and year determined in a meta-analysis for Europe, the United States and Canada, but is greater than the average costs calculated by Barry et al. [25] for England (€5137). According to the literature from Germany, medication costs account for the largest part of per patient costs, followed by hospitalisations [22, 24, 26]. In our current analysis, medication costs and hospitalisation were also the main cost drivers, reflecting a high OCS burden in association with the severity of the asthmatic disorder and comorbidities.

As a matter of principle, only billable data were registered as routine SHI data. These are collected at various interfaces in the healthcare system (e.g. physicians, pharmacists, hospitals), and inconsistencies and errors may occur, for example regarding confirmation of the asthma diagnosis [27]. This also relates to the potential other reasons for OCS use than asthma, including musculoskeletal and connective tissue disorders. Furthermore, eosinophilic granulomatosis with polyangiitis was not ruled out but, according to our analysis, only affected less than 0.5% of the population under investigation. Moreover, the total macroeconomic costs cannot be reflected conclusively, as only costs for a maximum of 6 weeks per year off work are covered by the SHI, while longer sickness absence, rehabilitation and early and partial retirement were covered by the pension fund. This may have led to distortions and loss of accuracy in further calculations (such as of the indirect costs) but more likely resulted in an underestimation of cost, rather than an overestimation. Distortions can also occur during the selection of billing codes (e.g. ICD-10 three-digit codes for comorbidities/adverse effects). For example, the percentage of OCS-induced conditions such as cataracts or osteopenia cannot be precisely estimated, since the groups of “eye disorders” or “skeletal muscle, connective tissue or bone disorders” can also include other diagnoses.

In conclusion, we have provided novel prevalence information that demonstrates that, despite maintenance therapy with HD-ICS/LABAs, severe asthma is inadequately controlled and requires the use of OCS maintenance therapy. It indicates that OCS therapy is applied at relatively high dosages in everyday care and is associated with many adverse effects, commonly reported with steroid usage. These data thus support a necessary change in the therapy of severe asthma, which is already reflected in national and international guidelines with the inclusion of biologics for respective patients.