Background Clinical assessment of rheumatoid arthritis (RA) patients may be challenging when objective measures, such as C-reactive protein (CRP), do not show elevated disease activity or when patients have concomitant, non-inflammatory pain, as occurs with fibromyalgia (FM). A multi-biomarker disease activity (MBDA) blood test has been developed to assess RA disease activity with a score, ranging from 1-100, that is calculated using a validated algorithm with 12 serum protein biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, YKL-40, MMP-1, MMP-3, leptin, resistin, SAA, CRP).
Objectives To evaluate the role of the MBDA score in the assessment of RA disease activity in a cohort of established RA patients, including patients with low CRP levels and those with and without concomitant FM.
Methods 208 RA patients from BRASS, a large prospective observational cohort, were randomly selected for a substudy of pain in RA. For the present cross-sectional study, DAS28-CRP components, the Widespread Pain Index (to diagnose FM by a modified version of the 2010 ACR Diagnostic Criteria for FM), and the MBDA blood test were obtained at the initial substudy visit. 198 of 208 patients had complete data and were included in this analysis. Participants were cross-categorized by level of CRP and of MBDA score. T-tests were used to compare DAS28-CRP, its components, and MBDA scores between RA patients with and without FM. In secondary analyses, the RA patients with FM were matched 1:1 with RA patients without FM using age, gender and swollen joint count (SJC) (± 2 joints).
Results Baseline values (mean or %) for N=198 were age 58 years; 85% female; disease duration 16 years; DMARD use: non-biologic 62%, biologic 61%; BMI 27; SJC-28 2.7; DAS28-CRP 2.9; MBDA score 32 (low: ≤29; moderate: 30-44; high: ≥45). Serum CRP levels were ≤1, >1 to 3, or >3 mg/dL in 184 (93%), 12 (6%), and 2 (1%) subjects, respectively (Table). Among those with CRP ≤1, MBDA scores were low in 51%, moderate in 36% and high in 13% (Table). Participants with RA+FM (N=25) had similar CRP, MBDA scores and SJC compared with RA patients without FM (n=173). In contrast, the 25 RA+FM patients had significantly greater mean values for patient global assessment (PGA) (50 vs. 15, p<0.001) and DAS28-CRP (3.6 vs. 2.8, p<0.01) and marginally greater TJC (6.6 vs. 4.0, p=0.06). Similar results were obtained comparing RA+FM patients with a matched, nested subset of 25 RA patients without FM.
Conclusions In patients with RA, values for PGA and DAS28-CRP score were significantly greater for those with FM than without FM, whereas CRP and MBDA scores were similar. MBDA appeared to differ from CRP, however, because, among patients with CRP ≤ 1 mg/dl, nearly half had MBDA scores in the moderate to high disease activity range, based on previously published thresholds. These results suggest that the MBDA score may provide information about disease activity that is not provided by standard assessment tools for RA. Further study is needed to determine the clinical meaning of discordance between CRP and MBDA scores.
Disclosure of Interest Y. Lee Shareholder of: Merck, Novartis, Cubist and Elan Corporation, Grant/research support from: Forest Research Institute, D. Haney Employee of: Crescendo Bioscience, Inc., C. Alexander Employee of: Crescendo Bioscience, Inc., M. Frits: None Declared, C. Iannacconne: None Declared, N. Shadick Grant/research support from: Crescendo Bioscience, Inc., Amgen, Abbott, and Genentech, O. Segurado Employee of: Crescendo Bioscience, Inc., M. Weinblatt Grant/research support from: MedImmune and Crescendo Bioscience, Inc., and Bristol Myers Squibb, Consultant for: MedImmune and Crescendo Bioscience, Inc., and Bristol Myers Squibb, E. Sasso Employee of: Crescendo Bioscience, Inc.