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Mortality Linked to History of Hospitalization in Patients With Systemic Lupus Erythematosus

“Systemic lupus erythematosus is a chronic inflammatory autoimmune disease where a variety of organ complications contribute to an increased risk of premature mortality,” investigators stated.

Patients with systemic lupus erythematosus (SLE) who were hospitalized due to their condition had an increased risk of mortality when compared with the general population, according to a study published in Lupus Science and Medicine.1 Aboriginal Australians, those who were socioeconomically disadvantaged, females, and younger patients (<40 years old) were at the highest risk.

“SLE is a chronic inflammatory autoimmune disease where a variety of organ complications, which often require intensive and/or long-term use of immunosuppressive medication, contribute to an increased risk of premature mortality,” investigators stated. “Beyond the attempt to manage the increased risk of premature mortality after a hospitalization for SLE, clinicians should be particularly mindful about managing comorbidity and modifiable risk factors, such as smoking, alcohol consumption and obesity, to improve survival in this patient population.”

This population-level cohort study used data linked by the Western Australian Data Linkage System to identify individuals. The Western Australian Rheumatic Disease Epidemiological Registry (WARDER) contains information on hospital stays, inpatient visits, cancer notifications, and deaths for over 200,000 patients with rheumatic disease, as well as 200,000 comparators.

Hospitalization information for patients with SLE between 1980 and 2013 were identified in the Hospital Morbidity Data Collection (HMCD). As 89% to 93% of patients with SLE are hospitalized during their disease, the SLE cohort represents, at minimum, moderate-to-severe disease activity.

A total of 2111 patients with SLE were matched (1:10) for age, sex, temporality, year of index, hospital contact, and Aboriginality to 22,110 controls. Socioeconomic status was determined using the Socio-economic Indices for Areas (SEIFA)-Index of Relative Socio-Economic Advantage and Disadvantage (IRSAD).

Causes of mortality were determined via the Death Register, which includes information on contributing causes of death. Causes were defined according to the Australian Institute of Health and Welfare’s Multiple causes of death: An analysis of all natural and selected chronic disease causes of death 1997–2007.

Univariate and multivariate Cox proportional hazards and competing risks regression models determined associations between SLE mortality and hospitalizations.

Hospitalized patients with SLE had a mean age of 43.96 years. Most patients in both the SLE cohort and control group were female (85.1% vs 83.4%, respectively). Smoking was reported in 20.5% of the SLE cohort and 13.2% of the control group, and 7.8% of patients with SLE were Aboriginal Australians, compared with 6.0% of the control group. Patients with SLE were more likely to have thromboembolic events, hypothyroidism, hypertension, nephritis, dyslipidemia, and proteinuria. They also were more likely to be smokers, obese, and have a history of harmful alcohol consumption.

During the study period, 548 (26.0%) deaths occurred in the SLE cohort compared with 2450 (11.6%) of controls. Patients with SLE were an average of 11.5 years younger (64.6 vs 76.05 years, p<0.001), died sooner after hospitalization (6.85 vs 7.43 years of follow-up, p<0.001), and were also more likely to die either in the hospital (71.5% vs 55.0%, respectively) or upon arrival (1.1% vs 0.9%, respectively). Increased risk of mortality was most significant in the time between 1980-1999 (adjusted hazard ratio [aHR] 1.42, 95% CI 1.20 to 1.70; p<0.001), however, it continued to remain numerically higher throughout the remainder of the study period (aHR 1.27, 95% CI 1.11 to 1.45; p<0.001).

Female patients with SLE had a higher risk of all-cause mortality when compared with males (aHR 2.11). Aboriginal Australians with SLE were the most vulnerable (aHR 3.32), although this may have been influenced by comorbidities and modifiable risk factors. The highest risk of mortality was seen in those with socioeconomic disadvantage (Q1: aHR 2.49). Patients under 40 years old were also at risk of SLE-related mortality (aHR 7.46) and an SLE diagnosis increased the age-adjusted and sex-adjusted standardized mortality ratio (SMR) when compared with the control group.

Hospitalization for patients with SLE showed an increased risk of death from infection (aHR 4.38), death from lymphatic and hematopoietic tissues (aHR 1.91), cardiovascular disease (aHR 2.09), cerebrovascular disease (aHR 1.39), renal disease (aHR 3.42), and respiratory disease (aHR 2.26). It was also associated with endocrine and metabolic diseases, neurological disease, skin disease, and mental health disorders.

The database may have missed a few milder SLE cases who were managed in outpatient or private practices. Additionally, SLE classification criteria could not be determined from the data analyzed. However, a previous study indicated that only a small percentage of patients with SLE were not hospitalized at some point over an 11-year period and mortality estimates were comparable to other studies. The SLE cohort to control cohort ratio approximates the 1:1000 prevalence in Western Australia, which strengthens the study. Investigators were also able to accurately identify outcomes for all patients using the Western Australia Death Registry mortality data.

“Hospital-ascertained patients with SLE were at an increased risk of all-cause and cause-specific mortality compared with hospital-based controls and the general population of Western Australia from 1980 to 2014,” investigators concluded. “Critically, our findings show that for moderate-to-severe SLE, the risk of premature mortality remained throughout the 2000 to 2014 period.”

Reference:

Raymond WD, Lester S, Preen DB, et al. Hospitalisation for systemic lupus erythematosus associates with an increased risk of mortality in Australian patients from 1980 to 2014: a longitudinal, population-level, data linkage, cohort study. Lupus Sci Med. 2021;8(1):e000539. doi:10.1136/lupus-2021-000539