Lupus-Related Mortality Has Declined, but Gap Remains

Diana Phillips

October 31, 2017

Mortality attributed to systemic lupus erythematosus (SLE) has declined significantly since the late 1960s, but the decrease in SLE-related deaths has not matched the reduction in all-cause mortality seen in the general population, new data show.

In addition, SLE-related mortality rates vary markedly by sex, race, and region, Eric Y. Yen, MD, from the Division of Rheumatology at the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues report in an article published online October 31 in the Annals of Internal Medicine.

To evaluate temporal and regional SLE mortality trends, and, in particular, to assess whether and to what degree recent diagnostic and treatment advances have influenced death rates associated with the chronic autoimmune disease, the investigators conducted a population-based study using data from the US National Vital Statistics System for 1968 through 2013.

During the study period, 50,249 deaths were attributed to SLE, according to death certificate information, compared with 100,851,288 non-SLE deaths.

From the national data, the investigators quantified age-specific mortality rates for SLE and non-SLE causes for each year as the number of deaths divided by the number of persons in the US general population. Across the 46-year period, all-cause mortality in the non-SLE population decreased by 43.9%, whereas SLE mortality decreased by only 24.4%, the authors report. In addition, the ratio of SLE to non-SLE mortality was 34.6% higher in 2013 than in 1968.

Unadjusted trend analysis shows that unlike the reductions in age-specific mortality rates in the non-SLE population, SLE mortality rates did not decrease linearly during the period of study. "After an initial decrease between 1968 and 1975, the SLE [age-specific mortality rate] increased steeply between 1975 and 1981 and continued to increase at a lower rate between 1981 and 1999 before decreasing again starting in 1999," the authors report. They also note that the reversal in the mortality uptrend began more than 10 years earlier in men than in women. The same pattern of an uptrend in SLE mortality followed by a decrease was observed in all four regions of the country, they write.

Changes in SLE incidence over time might partially explain the changing mortality trends, as might the availability of improved diagnostic tests and classification criteria, the authors suggest. It's also possible that unanticipated events associated with new therapies, such as increased drug toxicities associated with cyclophosphamide and azathioprine in the 1970s, influenced the death rate trends.

Looking at mortality patterns by race, SLE deaths did not increase significantly among whites or those in the Asian/American Indian/Alaska Native/Pacific Islander group during the study, but did increase significantly among blacks between 1975 and 1983, followed by a period of stability until 2002, after which they decreased.

"Increased SLE mortality in black persons might be attributable to more high-risk disease features, such as extensive cellular crescents in the kidneys," the authors suggest, noting that similar findings of increased mortality in black persons have been reported previously.

Meanwhile, multiple logistic regression analyses showed that, after adjusting for age, sex, race, and geographic region, the risk for SLE death was significantly lower in 2004 through 2008 than in 1999 through 2003, and decreased even further from 2009 through 2013. "Females had significantly higher risk than males, as did members of racial/ethnic minorities (black, [Asian/American Indian/Alaska Native/Pacific Islander], and Hispanic) relative to white persons, residents of the South or West relative to the Northeast, and persons aged 65 years or older relative to those aged 0 to 64 years," the authors report.

"Increased SLE mortality in older persons may be related to complications associated with increasing cumulative doses of immunosuppressive medications as well as SLE complications, such as atherosclerosis," the authors hypothesize. "Higher mortality in females might reflect the higher prevalence of SLE among them, although sex-associated genetic, hormonal, social, and environmental factors may also influence SLE mortality."

Interaction testing showed significant links between race/ethnicity and both sex and geographic region, "indicating that race/ethnicity modified the relationship among sex, geographic region, and SLE mortality," the authors write.

In an analysis stratified by race/ethnicity, SLE mortality risk was found to be higher in females than in males in all racial/ethnic groups, although the risk varied, with the largest adjusted odds ratio and mortality differences seen among non-Hispanic blacks and the smallest in non-Hispanic whites, the authors write.

Regionally, non-Hispanic whites in the South had the greatest mortality risk compared with those in other regions, whereas living in the West conferred a greater risk than other regions for the other racial/ethnic groups, the authors report. Possible explanations for these disparities might be geographic differences in the quality of care and interactions between genetic and nongenetic factors associated with race/ethnicity and geographic differences in environment, such as increased sunlight exposure, socioeconomic factors, and access to medical care, the authors state.

Additional research is warranted to better understand the trends in SLE mortality and the differences across patient subpopulations "Comprehensive examination of SLE mortality using prospective population-based data collection could be helpful in understanding the mechanisms of the disparities in SLE mortality and identifying potentially modifiable risk factors that might inform targeted research and public health programs to promote health equity across subpopulations and regions of the United States," they conclude.

The authors have disclosed no relevant financial relationships.

Ann Intern Med. Published online October 31, 2017. Abstract

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