The Impact of Systemic Lupus Erythematosus Flares on Clinical and Economic Outcomes: The CHAMOMILE Claims Database Study in Germany

Patients with SLE are faced with long-term clinical and economic burdens that substantially impact their quality of life and can also indirectly impact society [16, 17]. To fully understand the extent of the global burden of SLE, information must be evaluated across a range of patient populations and healthcare systems. As SLE is a chronic, progressive disease that can lead to irreversible organ damage [18] and increased long-term mortality risk [19], evaluations of disease burden should follow patients over many years to assess how disease progression affects resource utilization over time. The German BKK health insurance fund database [13], one of the country’s largest sickness funds with long-term records, allowed for such an evaluation; here, the CHAMOMILE study utilized the database to identify a large cohort of patients with up to 8 years of follow-up to characterize the longitudinal clinical and economic impacts of SLE flares in Germany. Flares during a patient’s first year of SLE diagnosis were associated with incidence and severity of future flares, glucocorticoid use, work-related productivity, HCRU, and costs, highlighting the importance of controlling flares and minimizing long-term glucocorticoid use in patients with SLE.

Greater baseline disease severity has been associated with increased likelihood and severity of SLE flares over the short term [2]. In the CHAMOMILE cohort, degree of baseline flare severity was related to patients’ future experiences with flares over the 8 years or less of follow-up. On average, patients who experienced moderate/severe baseline flares experienced a greater number of and more severe flares over the study than patients with no or mild baseline flares.

Possibly as a result of their baseline flare status, patients with moderate/severe baseline flares experienced greater glucocorticoid exposure. Guidelines for maintenance treatment recommend that patients taper daily glucocorticoid use to 5.0 mg or less if full withdrawal is not possible [11, 12], and 5.0 mg/day or less is considered a goal for clinical remission on treatment [20]. However, in CHAMOMILE patients with moderate/severe baseline flares, annual mean cumulative daily oral glucocorticoid dose exceeded 5.0 mg in every year of the study except year 4, suggesting that they were not able to taper glucocorticoids completely.

Of note, cumulative glucocorticoid dosages were higher in patients with no vs mild baseline flares in every study year. It is important to point out that “no flare at baseline” is not equivalent to “no disease activity”. Compared with the mild flare group, the no baseline flare group included more patients with renal manifestations, more using immunosuppressants, and more with severe SLE; mean SDI was higher in the no baseline flare group, as were the proportions of patients with renal, cardiovascular, and peripheral vascular damage. While the retrospective nature of our analysis limits our conclusions, some patients in the no flare group may have had severe (e.g., renal) manifestations in the past requiring high-dose glucocorticoid or immunosuppressant therapy. Our findings highlight the challenges of balancing the treatment goals of minimizing disease activity and preventing flares while maintaining the lowest possible glucocorticoid dose when increasing glucocorticoid dose remains an important tool for treating flares [11].

Flares, high disease activity, and increased glucocorticoid use contribute to organ damage in patients with SLE [8, 21, 22]. As expected because of the irreversible nature of organ damage [8], mean damage scores increased from baseline over time in all baseline flare subgroups. At baseline and for each of the 8 follow-up years, annual damage scores were highest in patients who experienced moderate/severe baseline flares, compared with patients with no or mild flares. After 5 years of follow-up and standard SLE treatment, the proportions of patients with organ/system involvement increased from baseline in every domain, doubling in gastrointestinal, gonadal, ocular, neuropsychiatric, and cardiovascular domains, suggesting a continued unmet need for adequate treatments that do not contribute to organ damage.

More severe SLE has been associated with higher HCRU and costs in numerous patient populations [23, 24]. In addition to costs associated with treating SLE, employment rates among patients with SLE tend to be lower than in the general population, and work disability is common [3, 16], providing additional economic burden. Consistent with these trends, in this cohort, patients with moderate/severe baseline flares experienced more days of work disability and more and longer hospital stays during the baseline year and in the eighth year of follow-up than patients with mild or no baseline flares. A previous German claims study using the BKK database found that moderate and severe SLE was associated with significantly higher HCRU and costs vs matched controls [13]. Although that study compared costs across 5 years by disease severity and the current study compared costs across 8 years by baseline flare severity, mean annual all-cause costs per capita were similar for patients with severe disease and those with moderate/severe baseline flares (approx. €8–11,000), supporting an association between disease activity and healthcare costs in this database.

As a result of their intermittent nature and the level of clinical detail required to measure flares, there are limited long-term assessments of the impact of SLE flares on HCRU outcomes and cost. Two studies of claims databases from the USA demonstrated that increased disease severity was associated with increased flare rates, greater HCRU, and higher costs [2, 5]. A retrospective observational study of patient medical records in Europe identified the annual number of severe SLE flares as the strongest predictor of medical costs, with annual costs almost doubling with each severe flare [24]. Here, severe flares were defined in part by hospital admission and, in the USA, inpatient costs were found to be the main all-cause cost driver within 90 days of a severe flare [5]. In our study, the mean total annual cost for patients with moderate/severe flares at baseline was more than twice that of patients with no flares. That patients with moderate/severe flares in their first year of SLE diagnosis continued to have higher average annual costs than patients with no or mild baseline flares across 8 years of follow-up reinforces the unmet need for effective treatments for SLE. Of note, annual costs also increased with the number of annual flares that year, highlighting the potential burden of any flare for a patient, irrespective of flare severity.

A strength of the current study is that it refines the algorithms used in the previous BKK study [13], expanding patient selection to include more patients and a longer follow-up period. Utilizing this very large patient database in this way allows for a more accurate description of the clinical course of SLE, a disease with highly variable presentation [3], and improves our ability to assess cumulative organ damage due to disease activity and glucocorticoid use.

This study has a few limitations. The cohort included 2088 patients with SLE, but these patients were all receiving treatment in Germany, and so the results may not be generalizable to other countries, especially those outside of the European Union. Additionally, outcomes were based on insurance reimbursement data, which are likely to be less complete than medical records/patient charts. Treatments included in the study were restricted to those prescribed for outpatient use and cumulative and daily glucocorticoid dosages were estimated on the basis of prescription claims, which cannot account for patient adherence. Examining the relationship between flare severity and economic burden is complicated by the inclusion of medication use and hospitalization in the definitions of the flare categories, which are inherently costly. However, the greater burden of more severe flares for patients with SLE extended beyond medication use and hospitalization to other HCRU measures and work disability, and continued for up to 8 years, highlighting the burden of moderate and severe flares for patients with SLE.