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

doi:10.1136/bmjopen-2019-031850

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

BMJ Open. 2020 May 21;10(5):e031850. doi: 10.1136/bmjopen-2019-031850.

Authors

Irene B Murimi-Worstell^{1

2}, Dora H Lin³, Henk Nab⁴, Hong J Kan⁵, Oluwadamilola Onasanya^{2

6}, Jonothan C Tierce^{1

2}, Xia Wang⁷, Barnabas Desta⁷, G Caleb Alexander^{1

2

8}, Edward R Hammond⁹

Affiliations

¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
² Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
³ Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA.
⁴ Inflammation & Autoimmunity, AstraZeneca, Cambridge, UK.
⁵ Center for Population Health IT, Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁶ Department of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁷ BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, USA.
⁸ Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁹ BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, USA edward.hammond@astrazeneca.com.

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Cohort Studies
Cross-Sectional Studies
Humans
Longitudinal Studies
Lupus Erythematosus, Systemic* / complications
Lupus Erythematosus, Systemic* / mortality
Severity of Illness Index