Active SLE Disease Activity, Damage Linked to Greater Mortality

In patients with systemic lupus erythematosus (SLE), disease activity and damage as measured by validated metrics are associated with increased mortality and damage accrual, according to the results of meta-analyses published in The Journal of Rheumatology.

Although both disease activity and damage are recognized as leading contributors to further damage and mortality in SLE, most Canadian rheumatologists do not formally evaluate disease activity or damage using standardized metrics such as the SLE Disease Activity Index (SLEDAI). This contrasts with the better integration of validated composite measures of disease activity into clinical practice by rheumatologists for rheumatoid arthritis or spondyloarthritis. This meta-analysis was performed to gather evidence to inform the upcoming Canadian recommendations for the assessment of SLE using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology.

The researchers identified 816 articles for full review, 102 of which met inclusion criteria, and 53 had extractable data. Of these articles, 33 described outcomes related to disease activity and 20 described damage-related outcomes.

The disease activity measures included the British Isles Lupus Assessment Group (BILAG) index, the SLEDAI and SLEDAI-2K, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI, Mexican SLEDAI, Systemic Lupus Activity Measure (SLAM) and the European Consensus Lupus Activity Measurement (ECLAM).

Increased mortality was observed in 6 studies that evaluated the effect of higher SLEDAI scores at baseline or over time (hazard ratio [HR], 1.14; 95% CI, 1.06-1.22). In addition, the odds of mortality (odds ratio [OR], 1.13; 95% CI, 1.06-1.22) were higher in patients with SLE with greater disease activity as measured by SLEDAI. Higher disease activity scores were also associated with greater damage in patients with SLE (OR, 1.08; 95% CI, 1.03-1.12) in 3 studies and 4 studies demonstrated increased risk for damage in patients with higher SLEDAI scores over time with a HR of 1.18 (95% CI, 1.02-1.37). Sensitivity analysis found an HR of 1.23 (95% CI, 1.15-1.32) for damage accrual related to a higher SLEDAI over time.

Worse BILAG scores also conferred a greater risk for damage, as did worse SLAM scores. While the results of some studies could not be combined for the meta-analyses, their results corroborate the finding of an association between higher disease activity as measured by SLEDAI, Mexican SLEDAI, BILAG, SLAM, or ECLAM, and greater mortality and damage accrual.

The authors concluded that validated metrics should be used in the assessment and monitoring of SLE. Measurement of disease activity and damage is not only essential to research, but also vital in daily practice. The results of the summary analysis will be included as part of the evidence-to-decision table in the anticipated Canadian SLE recommendations.

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Reference

Keeling SO, Vandermeer B, Medina J, et al. Measuring disease activity and damage with validated metrics: a systematic review on mortality and damage in Systemic Lupus Erythematosus [published online August 15, 2018]. J Rheumatol. doi:10.3899/jrrheum.171310