Discussion
This study of newly diagnosed patients with SLE in the USA identified a mean annual flare rate of 3.5 in the year following diagnosis, and an average of 36.4 days from diagnosis to first SLE flare. Patients with moderate and severe SLE had flare rates that were 1.7-fold and 1.9-fold higher, respectively, than those with mild SLE. Patients with moderate and severe SLE had a 1.4-fold and 1.6-fold shorter time to first SLE flare, respectively, than patients with mild disease. Our findings show the increasing mean healthcare costs of flares by 30 days through 90 days after a flare, with the largest healthcare costs attributable to severe flares occurring at 90 days. These findings highlight greater clinical and medical cost burden experienced by patients with moderate and severe SLE.
The annualised flare rates by disease severity observed in our study (2.2, 3.7 and 4.2 for patients with mild, moderate and severe SLE, respectively) are similar to those reported by Garris et al,3 who also used a claims-based algorithm in a similar study population. We further evaluated annualised flare rates by flare severity and found that rates of severe flare increased with increasing disease severity. Although our findings are slightly higher, similar trends were reported in a US Medicaid study population with a longer follow-up period,13 and may be a reflection of disease control over time.
Corticosteroids are the mainstay therapy used to manage SLE flares, supplementary to maintenance treatment.14 We observed frequent use of high-dose corticosteroids for moderate and severe flares sustained through 90 days post-flare. Prolonged corticosteroid use is associated with an increased risk of adverse effects and organ damage.15 16 Additionally, increased SLE disease activity and SLE flares are associated with organ damage accrual,17 18 with attendant high healthcare cost and increased mortality risk.19–22 In line with the treat-to-target initiative in SLE,23 any corticosteroid-sparing treatment to prevent flares may also reduce disease progression and associated healthcare costs.
In our study, 95% of newly diagnosed patients with SLE experienced ≥1 flare in the year after diagnosis, with 67% experiencing ≥3 flares. This finding could be due to delays between initial disease manifestation, diagnosis and initiation of appropriate medical therapy. Flare rates identified in this study are higher than previous estimates,2 possibly owing to different flare definitions or improved capacity to detect flares through our integration of both EMR and claims data. Data on flare rates in newly diagnosed patients with SLE are sparse; however, in a recent US commercial claims study, patients who were diagnosed earlier (<6 vs ≥6 months from symptom onset to diagnosis) experienced lower flare rates, healthcare utilisation and costs.24 Reducing disease activity, preventing flares and minimising drug toxicities are key treatment goals for patients with SLE that aim to improve patient outcomes and quality of life, and prevent organ damage.25 26 Our results highlight that pursuit of these treatment goals should begin early after diagnosis.
Our analyses demonstrated significant healthcare cost increases up to 90 days post-SLE flare. Healthcare costs were 10.1-fold higher for severe flares and 4.4-fold higher for moderate flares compared with mild flares. Previous studies have shown associations between flare severity and cost at 30 days and 1 year after flare3 6 13; however, all-cause healthcare costs per flare over the 30–90 days post-diagnosis have not been previously reported. Our evaluation of costs across multiple care settings identified that outpatient and inpatient stays account for 64%–90% of costs associated with moderate and severe flares at 30, 60 and 90 days after flare. The leading cost driver of severe flares in the year after diagnosis was inpatient visits, which accounted for 57%–72% of costs. This is consistent with a Canadian cohort study that also found 58% of all-cause medical costs during the year after SLE diagnosis were from hospitalisations.27 High healthcare costs in the first year after diagnosis may be the result of flares that require inpatient stay.
This study identified that 58.5% of patients with newly diagnosed SLE were from the South region of the USA, consistent with a study of 47 states and Washington, DC, that reported the highest SLE prevalence in the South (163.5 per 100 000) and the lowest in the Northeast (125.2 per 100 000) USA.28 Regional differences may reflect different patient demographics across regions, or the potential role of sunlight/ultraviolet light radiation exposure in the pathogenesis of SLE disease activity.29
There are some limitations to our findings. Most patients in the database were covered by commercial insurance (87.7%), with 12.3% covered by an employer-provided Medicare supplemental plan and did not include patients covered by Medicaid. However, by linking claims to EMR data, we captured a comprehensive view of SLE treatment and costs associated with flares. Since SLE disease and flare severity were classified using claims-based algorithms, there is potential for misclassification. Additionally, while the ability of the algorithm to define severity and calculate costs may be strengthened by using patient-level data (ie, inpatient stays), this may also introduce bias. Although we supplemented the algorithm with EMR data to improve its accuracy, occurrence and frequency of SLE flares may be potentially overestimated or underestimated. For example, we considered one flare to have ended when a flare of increased severity began, regardless of the interval between the two flares; this may overestimate flare counts. On the other hand, if the next flare was of lower severity and within 30 days, it was assumed to be a continuation of the same initial flare, potentially leading to underestimation of flare counts. Moreover, multiple inputs of the same code do not necessarily indicate multiple flares, as physicians use the same codes for patients who are in remission but are being monitored. However, given the similarities between our findings and those that have been previously published, we are confident in our application of the claims-based algorithms to the present study. Our study design intended to identify patients with incident SLE within the preceding year. The study population may have included prevalent SLE cases without a healthcare encounter or newly insured during the prior year. Furthermore, patients with lupus nephritis diagnoses pre-index were excluded and may have had higher healthcare costs than those with SLE.30 Cost estimates may also have been inflated because only patients who were receiving SLE medications were included in the analysis, meaning that some cases of mild SLE were probably excluded; however, this population is likely to be small and our exclusion criteria increased the specificity of our findings.
Strengths of our study include the use of the IBM MarketScan commercial claims database, which contains comprehensive healthcare resource utilisation data on real-world encounters of patients with SLE, including details on care settings and pharmacy claims. Data linkage with the GE EMR database allowed deeper evaluation of demographic and clinical information, such as race/ethnicity, diagnoses and written prescriptions. Together these data sources provided a comprehensive view of the study population that is not possible with use of a claims database alone because the data sources complemented and supported each other if patient data were missing within a single source. The data used in this work support a more detailed analysis of SLE flare costs than has been previously reported in studies using single data sources.3 4 13 31 Our work assessed healthcare costs at multiple time points during the interval after a flare, which has not been previously reported in patients with newly diagnosed SLE.
In conclusion, this retrospective cohort study of real-world patients with newly diagnosed SLE demonstrates that flare frequency and severity increase with disease severity in the first year after diagnosis. Additionally, the total all-cause healthcare cost after a flare increases with increasing flare severity from 30 through 90 days after flare. Preventing or decreasing the frequency and duration of flares may improve health outcomes and reduce healthcare costs for patients with SLE.