Background/Purpose:

The multi-biomarker disease activity (MBDA) blood test assesses disease activity in patients with rheumatoid arthritis (RA) using a validated algorithm to provide a score of 1 to 100. The Leiden Early Arthritis Clinic (EAC) has enrolled a population-based cohort of subjects within 2 years of RA diagnosis for long-term care. In a prior study of Leiden EAC patients receiving non-biologic-DMARDs (median RA duration 4.6 yrs.), the MBDA score was significantly better than DAS28-CRP for predicting radiographic progression. We now provide in-depth analyses of the relationship between MBDA score and radiographic progression, and the ability of MBDA score to add value to other measures for predicting radiographic progression.

Methods:

This retrospective study evaluated 271 clinic visits by 163 RA patients (1987 ACR criteria) of the Leiden EAC. Clinical and blood test data were obtained at each visit, with radiographs taken then and 1 year later. At first visit, patients were receiving only DMARDs and <5% received an anti-TNF subsequently. MBDA biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, MMP-3, YKL-40, leptin, resistin, SAA, CRP) were measured for each visit. Radiographic progression was assessed as change in Sharp van der Heijde score (DSHS) over one year. The association between MBDA score and radiographic progression was assessed by AUROC, by logistic quantile regression curves, and by relative risk (RR) vs. MBDA ≤25 for DSHS > 0, 3 or 5 units/yr. Frequency of DSHS >3 across MBDA categories (low: £29; moderate 30-44; high: >44) was assessed within categories of DAS28-CRP, CRP (£1,1-3 and >3 mg/dL) or serologic status (sero+: RF+ and/or CCP+; sero-neg: both negative), with p-values adjusted for multiple testing.

Results:

Characteristics of the 271 patient visits included median age 55 yrs., 67% female, 66%/69% RF+/anti-CCP+, median SHS 25, median MBDA score 41. The 75^th and 90^th quantile regression lines indicating risk of progression increased non-linearly with increasing MBDA score (AUROC = 0.72/0.77 for DSHS >3 or >5, p < 0.001). The increase was most prominent between groups with MBDA scores of 40-44 and 45-49. Risk increased within the high MBDA category (RR (95% CI) = 7.2 (2.4-22.6)/18.1 (6.5-29.1) for DSHS >3 or >5 for MBDA ³60). Within categories of DAS28-CRP or CRP, and for sero-neg and sero+ patients, the low/high MBDA score subgroups had significantly lower/higher rates of progression, respectively.

Conclusion:

In DMARD-treated patients with established RA, radiographic progression increased non-linearly with increasing MBDA score. High MBDA score was associated with increased progression even when DAS28-CRP or CRP were low, and regardless of serologic status. Low MBDA score was associated with infrequent progression. Thus, the MBDA score may help identify patients at risk for rapid radiographic progression and may add useful information to other assessments.