Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis

Irene B Murimi-Worstell, Dora H Lin, Henk Nab, Hong J Kan, Oluwadamilola Onasanya, Jonothan C Tierce, Xia Wang, Barnabas Desta, G Caleb Alexander, Edward R Hammond, Irene B Murimi-Worstell, Dora H Lin, Henk Nab, Hong J Kan, Oluwadamilola Onasanya, Jonothan C Tierce, Xia Wang, Barnabas Desta, G Caleb Alexander, Edward R Hammond

Abstract

Objective: At least half of patients with systemic lupus erythematosus (SLE) develop organ damage as a consequence of autoimmune disease or long-term therapeutic steroid use. This study synthesised evidence on the association between organ damage and mortality in patients with SLE.

Design: Systematic review and meta-analysis.

Methods: Electronic searches were performed in PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Sciences Literature for observational (cohort, case-control and cross-sectional) studies published between January 2000 and February 2017. Included studies reported HRs or ORs on the association between organ damage (measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score) and mortality. Study quality was assessed using the modified Newcastle-Ottawa assessment. Pooled HRs were obtained using the DerSimonian and Laird random-effects model. Heterogeneity was assessed using the Cochrane Q (Q) and I2 statistics.

Results: The search yielded 10 420 articles, from which 21 longitudinal studies were selected. Most studies (85%) were of high quality. For 10 studies evaluating organ damage (SDI) as a continuous variable and reporting HR as a measure of association, a 1-unit increase in SDI was associated with increased mortality; pooled HR was 1.34 (95% CI: 1.24 to 1.44, p<0.001; Q p=0.027, I2=52.1%). Exclusion of one potential outlying study reduced heterogeneity with minimal impact on pooled HR (1.33 (95% CI: 1.25 to 1.42), p<0.001, Q p=0.087, I2=42.0%). The 11 remaining studies, although they could not be aggregated because of their varying patient populations and analyses, consistently demonstrated that greater SDI was associated with increased mortality.

Conclusions: Organ damage in SLE is consistently associated with increased mortality across studies from various countries. Modifying the disease course with effective therapies and steroid-sparing regimens may reduce organ damage, improve outcomes and decrease mortality for patients with SLE.

Keywords: cardiology; dermatology; immunology; nephrology; rheumatology.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work. HN was an employee of AstraZeneca when this work was performed. HJK is a shareholder of GlaxoSmithKline. XW, BD and ERH are employees of AstraZeneca. GCA is Chair of the FDA’s Peripheral and Central Nervous System Advisory Committee, has served as a paid advisor to IQVIA, serves on the advisory board of MesaRx Innovations, is a member of OptumRx’s National P&T Committee and holds equity in Monument Analytics, a healthcare consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of screening process. aOne study included both health-related quality of life and mortality outcomes. Quality of life will be reported separately. ESRD, end-stage renal disease; LILACS, Latin American and Caribbean Health Sciences Literature; SLE, systemic lupus erythematosus.
Figure 2
Figure 2
Forest plot of HRs for the association between organ damage (1-point increase in SDI) and mortality for studies included in the meta-analysis (n=10 studies). SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.
Figure 3
Figure 3
Forest plot of association between organ damage and mortality in remaining studies with SDI as a continuous or binary variable. aReports the relative risk. SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.

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