46-Year Trends in Systemic Lupus Erythematosus Mortality in the United States, 1968 to 2013: A Nationwide Population-Based Study

Abstract

Background: No large population-based studies have been done on systemic lupus erythematosus (SLE) mortality trends in the United States.

Objective: To identify secular trends and population characteristics associated with SLE mortality.

Design: Population-based study using a national mortality database and census data.

Setting: United States.

Participants: All U.S. residents, 1968 through 2013.

Measurements: Joinpoint trend analysis of annual age-standardized mortality rates (ASMRs) for SLE and non-SLE causes by sex, race/ethnicity, and geographic region; multiple logistic regression analysis to determine independent associations of demographic variables and period with SLE mortality.

Results: There were 50 249 SLE deaths and 100 851 288 non-SLE deaths from 1968 through 2013. Over this period, the SLE ASMR decreased less than the non-SLE ASMR, with a 34.6% cumulative increase in the ratio of the former to the latter. The non-SLE ASMR decreased every year starting in 1968, whereas the SLE ASMR decreased between 1968 and 1975, increased between 1975 and 1999, and decreased thereafter. Similar patterns were seen in both sexes, among black persons, and in the South. However, statistically significant increases in the SLE ASMR did not occur among white persons over the 46-year period. Females, black persons, and residents of the South had higher SLE ASMRs and larger cumulative increases in the ratio of the SLE to the non-SLE ASMR (31.4%, 62.5%, and 58.6%, respectively) than males, other racial/ethnic groups, and residents of other regions, respectively. Multiple logistic regression showed independent associations of sex, race, and region with SLE mortality risk and revealed significant racial/ethnic differences in associations of SLE mortality with sex and region.

Limitations: Underreporting of SLE on death certificates may have resulted in underestimates of SLE ASMRs. Accuracy of coding on death certificates is difficult to ascertain.

Conclusion: Rates of SLE mortality have decreased since 1968 but remain high relative to non-SLE mortality, and significant sex, racial, and regional disparities persist.

Primary funding source: None.

Appendix Figure 1.

Trends in ASMRs from SLE and non-SLE causes and ratio of SLE to non-SLE mortality rates, by sex, race, and geographic region, 1968-2013. Results are shown as SLE ASMRs and non-SLE ASMRs per 100 000 persons and the ratio of SLE to non-SLE mortality rates. Data are displayed per calendar year of death, with lines fitted on the basis of joinpoint trend analysis. From 1968 through 2013, the annual number of SLE deaths ranged from 570 to 1210 among females, 126 to 216 among males, 490 to 885 among white persons, 177 to 468 among black persons, 20 to 73 among Asians/PIs/AIs/ANs, 136 to 242 among persons in the Northeast, 180 to 293 among persons in the Midwest, 233 to 630 among persons in the South, and 110 to 317 among persons in the West. Data for Asians/PIs plus AIs/ANs are shown only for 1979 through 2013 because data from before 1979 are unreliable due to a small number of annual SLE deaths (<20) in this subpopulation. Because information on Hispanic ethnicity on death certificates is available only after 1999, ethnicity was not included in the joinpoint analysis. The APC for each trend for each subpopulation is presented as stack bars below each panel. Each stack is segmented at the year in which the change in slope is statistically significant and is aligned with the trend line. The numbers in each stack denote the APC (95% CI). The shaded stacks indicate an increasing trend, and the unshaded stacks represent a decreasing or nonsignificant trend. AI = American Indian; AN = Alaska Native; APC = annual percentage change; ASMR = age-standardized mortality rate; MW = Midwest; NA = not available; NE = Northeast; PI = Pacific Islander; SLE = systemic lupus erythematosus. * P < 0.05 for slope change.

Appendix Figure 2.

Major SLE treatment milestones in relation to SLE mortality rates. The ASMR per 100 000 persons for SLE (Figure, top) is shown in relation to major SLE treatment milestones. Corticosteroids and hydroxychloroquine were introduced to treat patients with SLE in the 1950s (36, 37). Immunosuppressive drugs, including azathioprine (38) and daily oral cyclophosphamide (18), were introduced in the 1970s. The superiority of immunosuppressive drugs plus corticosteroids over corticosteroids alone was reported in the 1980s (39). Monthly IV cyclophosphamide was introduced in the 1980s (19, 20). Drugs that have more recently been used to treat SLE include mycophenolate, since the late 1990s (21); rituximab, since the mid-2000s; and belimumab, which was approved by the U.S. Food and Drug Administration to treat SLE in 2011 (22). ASMR = age-standardized mortality rate; AZA = azathioprine; BMM = belimumab; COR = corticosteroids; CYC = cyclophosphamide; HCQ = hydroxychloroquine; IV = intravenous; MMF = mycophenolate; RTX = rituximab; SLE = systemic lupus erythematosus.

Figure.

ASMRs for SLE and non-SLE causes and ratio of SLE to non-SLE mortality rates, 1968-2013. ASMRs per 100 000 persons for SLE and non-SLE causes are shown in the top and middle panels, respectively. Data are displayed per calendar year of death, with lines fitted on the basis of joinpoint analysis. The bottom panel shows the ratio of SLE to non-SLE ASMRs. A positive slope of the ratio indicates increased risk for death from SLE vs. non-SLE causes, and a negative slope indicates decreased risk. The APC for each trend in SLE ASMR, non-SLE ASMR, and the ratio of SLE to non-SLE ASMR is presented as stack bars under each panel. Each stack is segmented at the year in which the change in slope is statistically significant and is aligned with the trend line. Numbers in each stack denote the APC (95% CI). The shaded stacks indicate an increasing trend, and the unshaded stacks represent a decreasing or nonsignificant trend. APC = annual percentage change; ASMR= age-standardized mortality rate; SLE = systemic lupus erythematosus. * P < 0.05 for slope change.