Predicting risk for radiographic damage in rheumatoid arthritis: comparative analysis of the multi-biomarker disease activity score and conventional measures of disease activity in multiple studies

Abstract

Objective: To compare the multi-biomarker disease activity (MBDA) score with the DAS28-CRP and CRP for predicting risk of radiographic progression in patients with rheumatoid arthritis. Methods: Published studies of the MBDA score and radiographic progression with 100 patients per cohort were evaluated. Rates of radiographic progression over 1 year were determined across the low/moderate/high categories for MBDA score (low/moderate/high: <30, 30-44, >44), DAS28-CRP (low/ moderate/high: 2.67, >2.67-4.09, >4.09) and CRP (low/moderate/high: 10, >10-30, >30 mg/L), with positive and negative predictive value (PPV, NPV) and relative risk (RR) determined for high vs. not-high (i.e. low and moderate combined) categories. Patient-level data from studies having all three measures was pooled to: (1) determine a combined RR for radiographic progression in the high vs. not-high categories for each measure; and (2) compare the predictive ability of MBDA score vs. DAS28-CRP by comparing the rates of radiographic progression observed in subgroups created by cross-classifying the high and not-high categories of each measure. Results: Five cohorts were identified for inclusion (total N¼929). In each, radiographic progression was more frequent with increasing MBDA scores. Among the three cohorts with requisite data, PPVs were generally similar using categories of MBDA score, DAS28-CRP or CRP but NPVs were greater for MBDA score (93-97%) than DAS28-CRP or CRP (77-87%). RRs for radiographic progression were greater when based on categories of MBDA score than DAS28-CRP or CRP and the combined RR was greater for MBDA score (4.6, p < .0001) than DAS28-CRP (1.7, p ¼ .02) or CRP (1.7, p ¼ .002). For patients cross-classified by MBDA score and DAS28-CRP, high vs. not-high MBDA score significantly predicted radiographic progression independently of DAS28-CRP. Conclusions: High and not-high MBDA scores were associated with increased and low risk, respectively, for radiographic progression over one year. MBDA score was a better predictor of radiographic progression than DAS28-CRP or CRP.

Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis

“…Prior studies have reported that baseline MBDA score can predict risk for radiographic progression [11,[32][33][34], and that the MBDA score is a better predictor of radiographic progression than conventional measures of RA disease activity [33,35]. A study of patients with early RA found that lower MBDA scores in patients with inadequate clinical response to methotrexate monotherapy were associated with better clinical responses to subsequent triple therapy [36].…”

“…The biomarkers in the MBDA test reflect the biology of RA and consist of cytokine-related proteins (IL-6, TNF-R1), acute phase reactants (CRP, serum amyloid A), an adhesion molecule (VCAM-1), growth factors (EGF, VEGF-A), matrix metalloproteinases (MMP-1, MMP-3), and adipokines (leptin, resistin). The MBDA score is an integer on a scale of 1 to 100, with disease activity categories of low (< 30), moderate (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) and high (> 44) [10]. Minimally clinically important difference (MCID) for MBDA score is ≥8 [23].…”

A multi-biomarker disease activity score can predict sustained remission in rheumatoid arthritis

“…As expected, the median DAS28-ESR, DAS28-CRP, SDAI and CDAI at baseline (2.08, 2.50, 4.1 and 3.7, respectively) were all in the low category. The median (IQR) baseline MBDA score was 31 (18-39) and the median tiMBDA score was 29 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). The heatmap in Fig.…”

“…These 12 biomarkers reflect biological pathways involved in the pathogenesis of RA and can be broadly grouped as acute-phase reactants (SAA, CRP), hormones (leptin and resistin), growth factors (VEGF and EGF), adhesion molecules (VCAM1), skeletal-related proteins (YKL-40), matrix metalloproteinases (MMP-1, and cytokine-related proteins (IL-6, TNFR1). The MBDA score has been shown to predict risk for radiographic progression [20]. Therefore, these objective markers may be useful for defining remission on a molecular level and may have potential for predicting sustained remission.…”

Is It Time to Banish Composite Measures for Remission in Rheumatoid Arthritis?

“…Perhaps if defining remission in RA as 0 swollen joints is too difficult, then a biomarker could be a surrogate instead, such as the multibiomarker disease activity score (MBDA) or 14‐3‐3η protein . These measures correlate well with disease activity, and the MBDA may perform better than the CRP level or DAS28 score for radiograph progression , and even if in Simplified Disease Activity Index remission the 14‐3‐3η enzyme‐linked immunosorbent assay levels can predict radiographic progression , they are expensive and have not been tested to determine whether they provide added value to the physician global assessment or the actual SJC. The subspecialty of rheumatology should continue to use the joint assessment with the physical examination to define active RA and remission in RA.…”