Background/Purpose: A novel multi-biomarker disease activity (MBDA) score that is based on the serum concentrations of 12 biomarkers has been shown to correlate with clinical disease activity in patients with rheumatoid arthritis (RA) including patients treated with TNF inhibitors (TNFi). The purpose of this study is to explore the role of MBDA to predict radiographic progression in RA patients treated with TNFi.

Methods: The study was conducted at UOEH, Kitakyushu, Japan, on 141 patients who had received TNFi: adalimumab (ADA), etanercept (ETN) and infliximab (IFX), for at least 1 year. X-rays were taken at baseline (BL) and week 52 of treatment and change (Δ) in modified total Sharp score (mTSS) over 1 year was determined. Clinical disease activity, serum biomarkers were assessed at BL and week 52 in all 141 patients and at week 24 in a subset of 83 patients. Concentrations of VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, MMP-3, YKL-40, leptin, resistin, SAA and CRP were measured using a multiplex immunoassay and the MBDA score (1-100) was calculated using the validated Vectra DA algorithm. Correlations between ΔmTSS and disease activity measures (MBDA, DAS28-ESR, CRP) were examined using Spearman correlation. The association between ΔmTSS and maintenance of high/low MBDA score was assessed in the subset of 83 patients with clinical and biomarker data at all 3 time points (BL, week 24 and week 52) using Fisher’s exact test.

Results: At baseline, patients had mean (±SD) values of DAS28-ESR 5.7 (±1.1), MBDA score 61 (±18), disease duration 103 (±121) months, and mTSS 68 (±103). In the overall group of 141 patients, 102 (72%) patients had a ΔmTSS ≤0.5 (non-progressors) and 12 (9%) had a ΔmTSS >3 (clinically relevant radiographic progression) by week 52.  ΔmTSS correlated with the yearly average of both DAS28-ESR (r =0.26, p =0.002) and MBDA score (r=0.33, p <0.001).  Among the 12 patients with ΔmTSS >3 by week 52, 7 were EULAR good responders and, 8 had a high MBDA score >44. 

In the subset of 83 patients with clinical and biomarker data at BL, week 24 and week 52, 10 (12%) patients had ΔmTSS >3. ΔmTSS from BL to week 52 correlated with the MBDA score DAS28-ESR and CRP at week 24 and with ΔMBDA score from BL to week 24 (p <0.05).  Patients with high MBDA scores >44 for at least 2 of any of the 3 visits had a greater risk of radiographic progression (ΔmTSS >3; OR =14.9, p =0.002). Patients with a low MBDA score ≤29 for at least 2 of any of the 3 visits had a higher likelihood to be non-progressors (ΔmTSS ≤0.5; OR =13.9, p =0.002).   A logistics regression model showed that low MBDA score ≤29 at week 24 had additive association with non-progression (ΔmTSS ≤0.5) above low DAS28-ESR at week 24 (p =0.007).

Conclusion: In patients with RA treated over one year with TNFi, repeated low MBDA scores were associated with no radiographic progression while repeated high MBDA scores were associated with clinically relevant radiographic progression. Disease activity at 24 weeks post-treatment and change in MBDA score from BL to 24 weeks correlated with radiographic progression at 1 year.  At week 24, low MBDA score had additive association with good radiographic outcome above low DAS28-ESR alone.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/repeated-high-or-low-multi-biomarker-disease-activity-vectra-da-algorithm-scores-associated-with-radiographic-outcomes-in-patients-with-rheumatoid-arthritis-treated-with-tumor-n/