No validated and widely accepted biomarker for flare prediction in systemic lupus erythematosus (SLE) was found in a recent systematic review of literature, in spite of strong clinical interest in and numerous publications on biomarkers in SLE.
SLE flares are unpredictable in frequency and severity and may lead to substantial organ damage, thus increasing morbidity and mortality and resulting in higher health care costs, researchers noted.
Physicians need to identify patients who are at greater risk for flares, to make early diagnoses, and to initiate rapid treatment or consider preventative therapies, they stated, adding that despite the great clinical necessity, a biomarker with the potential to efficiently predict the occurrence of new SLE flares has not yet been identified.
Two independent investigators, Noémie Gensous and Aurélie Marti, conducted the first systematic review of literature to identify all of the currently available data on biological SLE flare predictors in a study published in Arthritis Research & Therapy.
Using 2 databases (MEDLINE and EMBASE) through April 2015, the researchers aimed to identify the most reliable biomarkers in the literature that could potentially be used as flare predictors in SLE. Congress abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) from 2010 to 2014 were also reviewed.
Interventional studies (randomized or non-randomized, controlled trials) and observational studies (case-control or cohort studies) were included. The studies considered involved adults with SLE and addressed the relationships between 1 or more defined biological tests and the occurrence of disease exacerbation.
The investigators independently extracted data from each study using a systematic data extraction form. Seven types of biomarkers performed routinely in clinical practice and 9 types of novel biological markers were evaluated. In total, 4668 records were retrieved from both databases, with the addition of 20 studies from reference lists of papers. Of these, 4126 studies did not meet the required criteria and 135 full-text articles across 69 publications were retained for complete screening.
Anti-double-stranded DNA antibodies (anti-dsDNA ab) were examined in 6 studies with heterogeneous results. Sensitivity ranged from 27.7% to 100%, specificity from 13% to 89.1%, positive predictive value (PPV) from 4.1% to 59%, and negative predictive value (NPV) from 67% to 97.5%.
Complement and complement split products were analyzed in 19 studies. These results were also inconsistent, although some complement split products (C3a, C4d, Ba, Bb, SC5b9) were found to be informative in predicting lupus flares, particularly C3a (1-2 months prior to disease flare, C3a levels increased significantly for all 10 patients studied who experienced flares later), C4d (highest sensitivity, 86.0%), and Bb (highest specificity, 81.0%).
Gensous N, Marti A, Barnetche T, et al. “Predictive biological markers of systemic lupus erythematosus flares: a systematic literature review.” Arthritis Res Ther. 2017 Oct 24;19(1):238. doi: 10.1186/s13075-017-1442-1446.