SLE mortality remains disproportionately high, despite improvements over the last decade

Abstract

Despite a marked improvement in 10-year survival for systemic lupus erythematosus (SLE) patients over the past five decades, mortality rates from SLE remain high compared to those in the general population. SLE was also among the leading causes of death in young women in the United States during 2000-2015. However, it is encouraging that SLE mortality rates and the ratios of SLE mortality rates to non-SLE mortality rates have decreased every year since the late 1990s. Despite this improvement, disparities in SLE mortality persist according to sex, race, age, and place of residence. Furthermore, demographic and geographic variables seem to modify the effect of each other in influencing SLE mortality, leading to interactions between sex/race/ethnicity-associated factors and geographic differences. In other words, individuals of the same sex/race/ethnicity had differences in SLE mortality depending on where they lived. These observations highlight SLE as an important public health issue. The recognition of SLE as a leading cause of death in the general population might spur targeted public health programs and research funding to address the high lupus mortality.

Keywords: Geographic region; leading cause of death; mortality; race; sex; systemic lupus erythematosus.

Figure 1. SLE mortality trends in relation to major SLE treatment milestones and changes in incidence

The ratio of SLE ASMR to non-SLE ASMR SLE is shown in relation to major SLE treatment milestones and changes in incidence rates over time. Corticosteroids and hydroxychloroquine were introduced to treat patients with SLE in the 1950s.^, Immunosuppressive drugs, including azathioprine and daily oral cyclophosphamide, were introduced in the 1970s and were associated with increased drug toxicities that were reduced to some extent with the introduction of intravenous pulse cyclophosphamide in the 1980s.^, Subsequent use of mycophenolate and combination therapy with induction and maintenance phases in the 1990s led to further reductions in drug-associated complications and greater efficacy. Rituximab has been used since the mid-2000s, and belimumab was approved by the U.S. Food and Drug Administration to treat SLE in 2011. The pattern of changes in mortality that we observed may reflect these therapeutic advances and potential benefits or complications of treatment. In addition, changes in SLE incidence over time could partially explain the observed changing trends in SLE mortality. In Minnesota, incidence of SLE tripled between 1950 and 1992, and in Spain, incidence increased from 1.9 cases per 100 000 persons in 1987 to 1991 to 4.5 cases per 100 000 persons in 1992 to 1996 before decreasing to 1.6 cases per 100 000 persons in 2002 to 2006. ASMR, age-standardized mortality rate; AZA, azathioprine; BMM, belimumab; COR, corticosteroids; CYC, cyclophosphamide; HCQ, hydroxylchloroquine; i.v., intravenous; MMF, mycophenolate mofetil; p.o., oral; RTX, rituximab.

Figure 2. SLE mortality associations with race/ethnicity and place of residence

SLE mortality associations with demographic and geographic variables were determined using multiple logistic regression analysis. The period of 1999–2013 was chosen for this analysis, since information on Hispanic ethnicity was not available prior to 1999. Total number of deaths in sample, 18,866. *Statistically significant relative to the reference group: White in the left panel Northeast census region of the United States in the middle panel, and Northeast for each of the four subpanels in the right panel. (Left and Middle Panels) Main effects. The adjusted odds ratios for race/ethnicities and geographic regions are shown, as predicted by the model, integrated across all other demographic/region/time characteristics. For example, the left panel shows the SLE mortality risk in the three non-white groups relative to white persons, integrated over all men and women, all age groups, all calendar periods, and all geographical regions. The middle panel shows the SLE mortality risk in the Midwest, South and West geographic regions relative to the Northeast, integrated over all men and women, all age groups, all calendar periods, and all race/ethnicities. (Right Panel) SLE mortality association with geographical regions stratified by race/ethnicity. Multiple logistic regression models included interaction terms. For each racial/ethnic group, SLE mortality risk was greater in all other regions relative to the Northeast census region of the United States, except for non-Hispanic black persons in the Midwest and Hispanic persons in the South and Midwest. Hispanic persons in the Midwest had significantly lower SLE mortality than those in the Northeast. In non-Hispanic white persons, residence in the South conferred the highest SLE mortality risk, but in the other 3 racial/ethnic groups, residents of the West had the highest risk. The largest regional disparity in SLE mortality risk was in the Asian/PI/AI/AN group in the West versus the Northeast; the next largest regional disparity was in Hispanic persons in the West versus the Midwest.