National Trends in Pediatric Systemic Lupus Erythematosus Hospitalization in the United States: 2000–2009

DISCUSSION

This retrospective serial cross-sectional analysis provides national estimates of US inpatient healthcare use trends for pediatric SLE over a decade. Using administrative data from the nationally representative KID, we identified about 27,000 US hospitalizations for pediatric SLE over a 4-year period. The characteristics of this national inpatient pediatric SLE cohort are consistent with previously reported age, race, and sex demographics of pediatric SLE populations^1,7,18,21. It is notable that almost half the cohort was 18–20 years of age, which likely reflects the onset of pediatric SLE during adolescence. Over half of the SLE hospitalizations (57%) were for those with SLE nephritis, which was expected given the significant morbidity and mortality association with SLE renal disease, and we found that this proportion was stable over time. Our study extends the work of Tanzer, et al, who found similar demographics and a high proportion of inpatients with SLE nephritis, using KID data from 2000 to 2006⁷.

We present previously unreported national US data on inpatient hospitalization and mortality rates for pediatric SLE. We found an average annual rate of 8.6 hospitalizations for pediatric SLE per 100,000 population. Given the estimated prevalence of childhood-onset SLE at 3 to 9 per 100,000 population¹, this estimated hospitalization rate suggests that children with SLE will have an average of 1–3 hospitalizations every year. Although not reflective of the rate per individual, it represents a substantial burden from the healthcare system perspective. Our estimate for average all-cause mortality in patients with SLE was 1%, and 1.4% for those with SLE nephritis, both higher than the rate of 0.3% for those without SLE. Encouragingly, we found that inpatient SLE deaths decreased significantly over time from 1% to 0.6%, paralleled by a decrease in those with SLE nephritis and a minor decrease for those without SLE. This downward trend may represent fluctuation over time, but we think it likely represents a real decrease in mortality given the similar trend in both SLE groups. We speculate that this observed decrease in inpatient SLE mortality may be attributable to several circumstances. Pediatric care for acute SLE flares may be improving owing to better access to outpatient and inpatient rheumatology and other subspecialty care; earlier diagnosis and treatment leading to less severe flares and improved longterm disease control; increased availability of newer and less toxic immunosuppressive treatments such as MMF and rituximab therapy with less cyclophosphamide exposure^8,9,10,11; and overall improved pediatric healthcare technology and intensive care.

While the above factors may be influencing the decreasing inpatient mortality rate for pediatric SLE, LOS appears to be unaffected and has not changed significantly over time. The longer LOS for pediatric SLE hospitalizations at 5.9 days compared to 3.6 days for those without SLE is indicative of high healthcare use for children with SLE. Further, the longer LOS is more pronounced for those with SLE nephritis, at 6.7 days. This confirms the work of Tanzer, et al, who also reported high healthcare use for pediatric SLE, especially in those with kidney disease, in comparison to other pediatric hospitalizations⁷. In contrast, however, we did not find a statistically significant increase in the LOS over time. The high resource use for inpatient pediatric SLE patients is likely due to the need for more invasive procedures, multispecialty and intensive care management for SLE, and particularly SLE nephritis, in comparison to other pediatric hospitalizations. This is supported by our findings that medication infusions, dialysis, blood transfusions, vascular catheterizations, and renal biopsies were the most common procedures for SLE inpatients. We also found a statistically significant increase in the rates of dialysis, blood transfusions, and vascular catheterization procedures over the study period. Thus there appears to be an increased volume of procedures occurring over time, perhaps due to increased procedure availability and improved patient survival resulting in higher procedure rates for continued chronic care. Although the direct effect of therapeutic advances on outcomes is currently unclear, enhanced resource use may be leading to decreased inpatient mortality and improved overall survival for patients with pediatric SLE. If this trend eventually translates into decreases in pediatric SLE hospitalization rate and LOS, then the resulting overall effect may be a decrease in healthcare use. We did not observe this effect over the decade of our study, and it is possible that this effect may not be seen until later in the disease course.

We found that several patient-specific risk factors were associated with worse outcomes. Patients with SLE nephritis had increased inpatient mortality and LOS, which is consistent with expected higher morbidity and mortality in this group. Older age was associated with increased inpatient mortality, likely due to increasing complications of SLE and its treatment with age. Similarly, the increased mortality risk and LOS for patients of nonwhite race is consistent with findings of more severe SLE in nonwhite populations^18,19. Medicaid patients had an increased LOS, suggesting a role for lower socioeconomic status in the risk for worse outcomes, but we did not find an association with SLE mortality, as previously reported²². For hospital-specific factors, location in the South region was associated with increased mortality, for reasons that are unclear. Although there was a higher proportion of nonwhite and Medicaid patients in this region (data not shown) with potentially higher disease severity, location in the South region was an independent risk factor, and this may be due to other unmeasured factors related to SLE disease severity.

Our study presents the first estimates, to our knowledge, of inpatient hospitalization and mortality rates for pediatric SLE in the United States, as well as relevant healthcare use trends. The strength of our study lies in the large number of observations representative of the national pediatric SLE population. Despite this, a potential limitation is the lack of validation for the single ICD-9-CM code of 710.0 for identification of SLE using administrative data, which could lead to inaccurate outcome estimates; however, the code has been validated in coding algorithms using administrative data for identification of patients with SLE nephritis¹². Importantly, we identified those with nephritis as a significant proportion of the SLE inpatients with higher healthcare use and mortality rates, and it is possible that the prevalence of nephritis may actually be higher if patients were admitted for another reason, and the recorded ICD-9-CM codes did not reveal a history of nephritis. Unfortunately, we were unable to characterize other clinical manifestations and disease severity; the KID does not contain clinical details; and severity measures, such as the All Patient Refined Diagnosis Related Groups, were not available for all years of interest, and were not reliable because coding algorithms changed over time.

Our analysis of healthcare use trends over a decade provides valuable insight into the burden of SLE care from both the patient and healthcare system perspectives. Overall resource use by patients with SLE, and especially those with nephritis, has remained high; however, we were unable to determine individual patient burden because patients could not be tracked over time owing to the lack of unique patient identifiers in the KID, and some patients may be represented more than once in the dataset. We thus think that our estimates are especially meaningful from an overall healthcare burden perspective, and we indeed found a high average LOS for patients with SLE who are likely to have repeated hospitalizations during the course of their chronic disease, compared to those without SLE. Our finding of increasing rates of common therapeutic procedures also reflects the high overall healthcare burden for pediatric SLE. Coding practices may have affected the completeness of ICD-9-CM procedure codes, because the recorded codes may be more representative of invasive procedures (such as dialysis) than noninvasive procedures (such as magnetic resonance imaging), but our data still shed light on the frequency of invasive and often more costly procedures. Further evaluation of national healthcare costs for pediatric SLE would be a helpful additional measure of healthcare use; however, we were unable to accurately evaluate costs in the KID because of unavailability, missingness, and imprecision of cost-to-charge ratios for the years of study. Given the potential effect of MMF and other new treatment regimens, detailed analysis of the relationship between trends in specific treatments and the outcomes of interest would also be informative, but we were unable to address this because of the lack of itemized billing information in the KID.

We present novel data that raise interesting questions relevant to the patient and healthcare system burden of inpatient care as well as survival for patients with pediatric SLE. While our findings indicate that the US national hospitalization rate and LOS have remained stable for pediatric SLE, they represent a significant disease burden compared to those without SLE. The rates of common therapeutic procedures are increasing, while inpatient mortality is decreasing. Therefore, overall outcomes may be improving for patients with pediatric SLE, but certain groups remain at high risk for increased healthcare use and death. More research is needed to understand the role of advances in treatment and healthcare technology in the changing course of pediatric SLE healthcare use and survival.