SLE-related Mortality Research Articles

The Link Between Dysregulated Immunometabolism and Vascular Damage: Implications for the Development of Atherosclerosis in Systemic Lupus Erythematosus and Other Rheumatic Diseases.

A bimodal pattern of mortality in systemic lupus erythematosus (SLE) exists. Early-stage deaths are predominantly caused by infection, whereas later-stage deaths are mainly caused by atherosclerotic disease. Further, although SLE-related mortality has reduced considerably in recent years, cardiovascular (CV) events remain one of the leading causes of death in people with SLE. Accelerated atherosclerosis in SLE is attributed to both an increase in traditional CV risk factors and the inflammatory effects of SLE itself. Many of these changes occur within the microenvironment of the vascular-immune interface, the site of atherosclerotic plaque development. Here, an intimate interaction between endothelial cells, vascular smooth muscle cells, and immune cells dictates physiological vs pathological responses to a chronic type 1 interferon environment. Low-density neutrophils (LDNs) have also been implicated in eliciting vasculature-damaging effects at such lesion sites. These changes are thought to be governed by dysfunctional metabolism of immune cells in this niche due at least in part to the chronic induction of type 1 interferons. Understanding these novel pathophysiological mechanisms and metabolic pathways may unveil potential innovative pharmacological targets and therapeutic opportunities for atherosclerosis, as well as shed light on the development of premature atherosclerosis in patients with SLE who develop CV events.

In-hospital mortality in patients with systemic lupus erythematosus: a study from Jordan 2002-2017.

We aimed to study the mortality among hospitalized patients with systemic lupus erythematosus (SLE). We performed a retrospective cross-sectional study and identified patientswithSLEwho were hospitalized at Jordan University Hospital (JUH) between 2002 and 2017.There were 990 admissions among which 283 were SLE patients. The mean age at disease onset was 34 ± 12.5years and the female to male ratio was 8.4:1. Forty patients died during the 15-year period. In-hospital case fatality was 14% over 15years. For the deceased patients, the female to male ratio was 3.4:1, mean age at disease onset was 27.8 ± 11.5years, mean age at death was 35.1 ± 12years, and mean disease duration was 7.5 ± 6.9years. Twenty patients had disease duration ≤ 5years. Infection and SLE-related complication contributed equally to mortality in hospitalized SLE patients (42.5% [CI 27.5%-59%] and 40% [95% CI 25%-56.5%], respectively). Infection related mortality compared to SLE-related mortality was associated with younger age and shorter disease duration (29.5years versus 38.3years and 6.4 versus 8.7years, respectively). CRP was higher in infection related mortality compared to SLE-related mortality (131.4mg/dl versus 87.6mg/dl, respectively). Most SLE-related deaths were secondary to pulmonary disease. Renal disease did not contribute directly to mortality. No fatalities were attributed to cardiovascular disease (CVD) or cancer. Infection and active SLE accounted for the majority of deaths at a young age. Significant pulmonary related deaths may indicate a change in trends in SLE mortality, as renal related mortality is expected to decline due to proper management.

Unraveling Race, Socioeconomic Factors, and Geographical Context in the Heterogeneity of Lupus Mortality in the United States.

ObjectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune disease disproportionately affecting women and racial/ethnic minorities. We examined SLE‐related mortality over time to assess whether the impact of race is attenuated when social economic status (SES) and geographic context are also considered.MethodsThis study examined whether social environment attenuates racial disparities in SLE‐related mortality using race‐geographical combinations of the US population known as the “Eight Americas.” This framework jointly characterizes race, SES, and geographical location in relation to health disparities in the United States. Using National Vital Statistics and US Census data, we estimated mortality parameters for each of the Eight Americas.ResultsWe identified 24 773 SLE deaths (2003‐2014). Average annual mortality rates were highest among blacks in three race‐geographical contexts: average‐income blacks, southern low‐income blacks, and high‐risk urban blacks (14 to 15 deaths per million population) and lowest among nonblacks living in average‐income settings (3 to 4 deaths per million population). Age at death was lowest (~47.5 years) for blacks and Asians and highest among low‐income rural whites (~64.8 years).ConclusionBlacks sharing the same social and geographical contexts as whites were disproportionately more likely to die young. Although blacks inhabited three vastly different contexts, SLE‐related mortality parameters did not vary among socially advantaged and disadvantaged blacks. These findings suggest that race may transcend SES and geographical parameters as a key determinant of SLE‐related mortality.

Evaluating The Addition To Formulary of Belimumab For The Treatment of Systemic Lupus Erythematosus: A Cost-Effectiveness Model

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that causes potentially irreversible organ damage. A previous cost-effectiveness model (CEM) evaluating intravenous belimumab in SLE was a patient microsimulation model with a series of risk equations describing disease activity and survival models to depict time to organ damage. This model was substantially revised to use a semi-Markov model that still captures the complexity of SLE and analyses subcutaneous belimumab. Post hoc regression analyses of the intravenous belimumab US long-term extension study (BEL112233) and the Toronto Lupus Cohort were conducted to identify drivers of utilities, disease progression and SLE-related mortality (HO-15-15879/206347). Costs were based on LUCIC (Systemic LUpus Erythematosus Cost of Care in Canada; 114745). Results demonstrated that the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) and the presence of cardiovascular damage were sufficient to capture organ damage effects. Thus, health states were defined by treatment, SDI score and presence/absence of cardiovascular damage. The model uses a 1-year cycle length to analyse over a modifiable lifetime time horizon. Patient distribution at time=0 and Year 1 outcomes are based on source clinical trials. Thereafter, disease activity measured by adjusted mean SLEDAI (AMS), flares, and probability of organ damage progression are modelled separately for each health state and dynamically updated each cycle. Health state costs and utilities are based on multivariate regression analyses that increment payoffs for each cycle. A new CEM framework was developed within a Markov model, which further allowed incorporation of AMS, flares and organ damage progression in SLE. Total costs and outcomes were similar to the previous CEM. This modelling study has simplified clinical assumptions of SLE to produce a Markov model that may be used by additional stakeholders due to its increased transparency and shorter run time. Study funded by GSK.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n = 35), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32) and other causes (n = 21). Uni- and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

Mortality Risks Associated With Specific Clinical Manifestations of Systemic Lupus Erythematosus

Mortality in patients with systemic lupus erythematosus (SLE) is often related to disease in particular organ systems. We examined the risks of mortality associated with 8 clinical manifestations of SLE and determined whether these risks differed among patients with different sociodemographic characteristics. Using life table analysis, we determined the associations of hemolytic anemia, leukopenia, thrombocytopenia, arthritis, serositis, nephritis, psychosis, and seizures with both all-cause mortality and SLE-related mortality in a cohort of 408 patients. Over a median duration of follow-up of 11 years, 144 patients died; 78 deaths (54%) were SLE related. In univariate analyses, the presence of hemolytic anemia, serositis, nephritis, psychosis, and seizures was associated with greater all-cause mortality, while the presence of arthritis was protective. In multivariate analyses that controlled for patient demographic characteristics, nephritis (relative risk, 2.34) and seizures (relative risk, 1.77) were associated with poorer overall survival. Nephritis and seizures, along with thrombocytopenia, were also associated with greater SLE-related mortality, while leukopenia was protective. The risk of death in association with these clinical manifestations did not differ among patient age, sex, race, or socioeconomic subgroups. The presence of nephritis and seizures each increased the risk of death in patients with SLE approximately 2-fold. Thrombocytopenia also increased the risk of SLE-related mortality, while leukopenia was protective.

Long-term survival in systemic lupus erythematosus. Patient characteristics associated with poorer outcomes.

To investigate the associations of age, sex, race, and socioeconomic status with long-term survival in patients with systemic lupus erythematosus (SLE). We examined survival in an inception cohort of 408 patients with SLE. The cohort included 177 black females, 162 white females, 49 white males, and 20 black males. The median duration of followup was 11 years (range 0.1-22 years). One hundred forty-four patients died during the study. The 5-, 10-, and 15-year survival estimates for the entire cohort were 82%, 71%, and 63%, respectively. In univariate analyses, mortality rates increased with age and were higher among males, blacks, those without private medical insurance, and those living in census tracts with lower household incomes. In multivariate analyses, age, sex, and both socioeconomic indicators were associated with total mortality (mortality from any cause), while race was not. Lower socioeconomic status and increased age were also associated with higher rates of death from SLE. Socioeconomic status, but not race, is associated with mortality in SLE. SLE-related mortality also tends to increase with age, which suggests that SLE may not be less severe when it occurs later in life.