Mortality in patients with systemic lupus erythematosus: A meta-analysis of overall and cause-specific effects

Abstract

Objectives

Our objective was to assess the overall and cause-specific standardized mortality ratios (SMRs) among patients diagnosed with systemic lupus erythematosus (SLE).

Methods

An exhaustive systematic review was undertaken, encompassing studies that scrutinized SMRs, both overall and for specific causes, in patients diagnosed with SLE compared to the general populace. The databases of PUBMED, EMBASE, and Cochrane were meticulously searched to collate relevant literature. Following this comprehensive search, a meta-analysis was executed to methodically assess all-cause, sex-specific, ethnicity-specific, and cause-specific SMRs in individuals with SLE.

Results

The inclusion criteria were met by 29 studies encompassing 72,342 patients with SLE and documenting 7352 deaths. The meta-analysis disclosed a pronounced 2.87-fold elevation in the SMR for all-cause mortality in SLE patients relative to the general population (SMR, 2.866; 95% confidence interval [CI], 2.490–3.242; p < .001). Region-specific assessments showed variable all-cause SMRs, with Europe reporting 2.607 (95% CI, 1.939–3.275; p < .001), Asia revealing 3.043 (95% CI, 2.082–4.004; p < .001), and particularly high SMRs noted in North America and Oceania. Gender-focused analyses presented a pooled SMR of 3.261 (95% CI, 2.674–3.848; p < .001) for females, and 2.747 (95% CI, 2.190–3.304; p < .001) for males. Evaluations specific to cause of death illustrated notably elevated SMRs for renal disease (SMR, 4.486; 95% CI, 3.024–5.948; p < .001), infections (SMR, 4.946; 95% CI, 4.253–5.639; p < .001), cardiovascular diseases (CVD) (SMR, 2.931; 95% CI, 1.802–4.061; p < .001), cerebrovascular accidents (CVA) (SMR, 1.588; 95% CI, 0.647–2.528; p = .001), and cancer (SMR, 1.698; 95% CI, 0.871–2.525; p < .001).

Conclusions

This meta-analysis underscores a significant 2.87-fold elevation in the SMR among patients with SLE compared to the general population, transcending differences in sex or geographical regions. Moreover, an appreciable increase in mortality due to specific causes, including renal disease, infection, CVD, CVA, malignancy, and neuropsychiatric SLE, accentuates the imperative for targeted interventions to mitigate these elevated risks in SLE patients.

Keywords

Systemic lupus erythematosus mortality meta-analysis

Get full access to this article

View all access options for this article.

References

Han

J-Y

Cho

S-K

Sung

Y-K

. Epidemiology of systemic lupus erythematosus in Korea. Journal of Rheumatic Diseases 2023; 30: 211–219. DOI: 10.4078/jrd.2023.0037.

Manger

Repp

, et al. Definition of risk factors for death, end stage renal disease, and thromboembolic events in a monocentric cohort of 338 patients with systemic lupus erythematosus. Ann Rheum Dis 2002; 61: 1065–1070.

Bernatsky

Boivin

Joseph

, et al. Mortality in systemic lupus erythematosus. Arthritis and Rheumatism - Arthritis Care and Research 2006; 54: 2550–2557.

Borchers

Keen

Shoenfeld

, et al. Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun Rev 2004; 3: 423–453.

Julious

Nicholl

George

. Why do we continue to use standardized mortality ratios for small area comparisons? J Publ Health Med 2001; 23: 40–46.

Tselios

Gladman

Sheane

, et al. All-cause, cause-specific and age-specific standardised mortality ratios of patients with systemic lupus erythematosus in Ontario, Canada over 43 years (1971–2013). Ann Rheum Dis 2019; 78: 802–806, annrheumdis-2018-214802.

Ingvarsson

Landgren

Bengtsson

, et al. Good survival rates in systemic lupus erythematosus in southern Sweden, while the mortality rate remains increased compared with the population. Lupus 2019; 28: 1488–1494.

Zen

Salmaso

Amidei

, et al. Mortality and causes of death in systemic lupus erythematosus over the last decade: data from a large population-based study. Eur J Intern Med 2023; 112: 45–51.

Hao

Fan

, et al. Mortality and prognostic factors in Chinese patients with systemic lupus erythematosus. Lupus 2018; 27: 1742–1752.

10.

Kedves

Kósa

Kunovszki

, et al. Large-scale mortality gap between SLE and control population is associated with increased infection-related mortality in lupus. Rheumatology 2020; 59: 3443–3451.

11.

Moe

Haukeland

Brunborg

, et al. Persisting mortality gap in systemic lupus erythematosus; a population-based study on juvenile-and adult-onset SLE in Norway 1999–2022. Rheumatology 2023; 00: 1–19. DOI: 10.1093/rheumatology/kead519.

12.

Yang

Xie

, et al. Causes of death in hospitalized patients with systemic lupus erythematosus: a 10-year multicenter nationwide Chinese cohort. Clin Rheumatol 2019; 38: 107–115.

13.

Taylor

Anastasiou

, et al. Causes of death among individuals with systemic lupus erythematosus by race and ethnicity: a population‐based study. Arthritis Care Res 2023; 75: 61–68.

14.

Raymond

Lester

Preen

, 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: e000539.

15.

Joo

Park

S-Y

Won

, et al. Differences in clinical features and mortality between childhood-onset and adult-onset systemic lupus erythematosus: a prospective single-center study. J Rheumatol 2016; 43: 1490–1497.

16.

Lao

White

Rabindranath

, et al. Mortality and causes of death in systemic lupus erythematosus in New Zealand: a population-based study. Rheumatology 2023; 00: 1–8. DOI: 10.1093/rheumatology/kead427.

17.

Duarte-García

Hocaoglu

Valenzuela-Almada

, et al. Rising incidence and prevalence of systemic lupus erythematosus: a population-based study over four decades. Ann Rheum Dis 2022; 81: 1260–1266.

18.

Gianfrancesco

Dall’Era

Murphy

, et al. Mortality among minority populations with systemic lupus erythematosus, including Asian and Hispanic/Latino persons—California, 2007–2017. MMWR (Morb Mortal Wkly Rep) 2021; 70: 236.

19.

Ambrose

Morgan

Galloway

, et al. Differences in disease phenotype and severity in SLE across age groups. Lupus 2016; 25: 1542–1550.

20.

Voss

Laustrup

Hjelmborg

, et al. Survival in systemic lupus erythematosus, 1995-2010. A prospective study in a Danish community. Lupus 2013; 22: 1185–1191. DOI: 10.1177/0961203313498796.

21.

See

Kuo

, et al. Prevalence and incidence in patients with autoimmune rheumatic diseases: a nationwide population-based study in Taiwan. Arthritis Care Res 2013; 65: 244–250. DOI: 10.1002/acr.21820.

22.

Gustafsson

Simard

Gunnarsson

, et al. Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study. Arthritis Res Ther 2012; 14: R46. DOI: 10.1186/ar3759.

23.

Mok

Kwok

, et al. Life expectancy, standardized mortality ratios, and causes of death in six rheumatic diseases in Hong Kong, China. Arthritis Rheum 2011; 63: 1182–1189. DOI: 10.1002/art.30277.

24.

Hersh

Trupin

Yazdany

, et al. Childhood-onset disease as a predictor of mortality in an adult cohort of patients with systemic lupus erythematosus. Arthritis Care Res 2010; 62: 1152–1159. DOI: 10.1002/acr.20179.

25.

Hashkes

Wright

Lauer

, et al. Mortality outcomes in pediatric rheumatology in the US. Arthritis Rheum 2010; 62: 599–608. DOI: 10.1002/art.27218.

26.

Mok

Tang

, et al. Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis. Lupus: Int J 2009; 18: 1267–1275.

27.

Mok

, et al. Incidence and mortality of systemic lupus erythematosus in a southern Chinese population, 2000-2006. J Rheumatol 2008; 35: 1978–1982.

28.

Bernatsky

Boivin

Joseph

, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum 2006; 54: 2550–2557. DOI: 10.1002/art.21955.

29.

Chun

Bae

. Mortality and cancer incidence in Korean patients with systemic lupus erythematosus: results from the Hanyang lupus cohort in Seoul, Korea. Lupus 2005; 14: 635–638.

30.

Bjornadal

Yin

Granath

, et al. Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964-95. J Rheumatol 2004; 31: 713–719.

31.

Alamanos

Voulgari

Papassava

, et al. Survival and mortality rates of systemic lupus erythematosus patients in northwest Greece. Study of a 21-year incidence cohort. Rheumatology 2003; 42: 1122–1123.

32.

Jacobsen

Petersen

Ullman

, et al. Mortality and causes of death of 513 Danish patients with systemic lupus erythematosus. Scand J Rheumatol 1999; 28: 75–80.

33.

Uramoto

Michet

Jr. Thumboo

, et al. Trends in the incidence and mortality of systemic lupus erythematosus, 1950-1992. Arthritis and Rheumatism - Arthritis Care and Research 1999; 42: 46–50.

34.

Lerang

Gilboe

Steinar Thelle

, et al. Mortality and years of potential life loss in systemic lupus erythematosus: a population-based cohort study. Lupus 2014; 23: 1546–1552. DOI: 10.1177/0961203314551083.

35.

Lee

Choi

, et al. Overall and cause-specific mortality in systemic lupus erythematosus: an updated meta-analysis. Lupus 2016; 25: 727–734.

36.

Lee

. An overview of meta-analysis for clinicians. Kor J Intern Med 2018; 33: 277.

37.

Davey Smith

Egger

. Meta-analyses of randomised controlled trials. Lancet 1997; 350: 1182.

38.

Higgins

Thompson

. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–1558. DOI: 10.1002/sim.1186.

39.

Egger

Davey Smith

Schneider

, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

40.

Duval

Tweedie

. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56: 455–463.