BIOMARKER SIGNATURES IN RHEUMATOID ARTHRITIS PATIENTS WITH LOW DISEASE ACTIVITY: THE REMIRA STUDY

Background: With intensive therapy, low disease activity (LDA) states are becoming increasingly common in patients with RA; remission rates now exceed 40% in clinical studies [1]. Conventional tools perform poorly in discriminating true remission from persistent sub-clinical disease. There is now an urgent need to improve the definition of LDA by using a wider range of clinical and laboratory variables. Vectra™ DA, a recently validated test for RA disease activity, combines 12 serum biomarkers to produce a multi-biomarker disease activity (MBDA) score between 1 and 100. We aim to investigate the use of this panel in assessing LDA patients in the REMIRA cohort. Objectives: To examine the use of the 12 MBDA biomarkers in assessing the heterogeneity of LDA states and to evaluate the MBDA score for differentiating between LDA/remission and LDA/non-remission states. Methods: RA patients on stable therapy with <10 yrs disease duration and DAS28ESR <3.2 were recruited to the REMIRA study; serum samples were acquired at baseline. Concentrations of 12 protein biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, YKL-40, MMP-1, MMP-3, leptin, resistin, SAA, CRP) were determined by immunoassay and used to generate MBDA scores by applying a pre-specified algorithm. The association between the MBDA score and DAS28CRP was assessed by calculating the area under the ROC curve (AUROC), where a DAS28CRP cut-off of 2.32 was used to define LDA/remission vs. LDA/non-remission. Comparison of biomarker concentrations was performed using the Wilcoxon test and a fixed-sequence procedure to control for the effects of multiple testing. Results: 70 RA patients with mean age of 58 (SD=14) and disease duration of 50 months (SD=31) were recruited to the study. 61% were female, 82% were Caucasian, 14% were Afro-Caribbean, and 4% were Asian. 68% were seropositive. Mean DAS28ESR was 1.84 (SD=0.83); mean DAS28CRP was 1.98 (SD=0.69). There was a statistically significant association between the MBDA score and DAS28CRP remission vs. non-remission (AUROC=0.75; 95% CI=(0.59,0.87)). When comparing levels of individual biomarkers in LDA/remission and LDA/non-remission, significant differences were found for IL-6, CRP, and SAA. Although pro-inflammatory biomarkers were generally lower in LDA/remission, a small subgroup of patients had elevated biomarkers and MBDA scores despite low clinical activity as judged by CRP, ESR, and swollen joint counts. Table 1. Concentrations of biomarkers differing beween LDA Remission and LDA Non-Remission BiomarkerMedian (IQR)p-value LDA RemissionLDA Non-Remission IL-6 (pg/mL)6.7 (5.5-10)12 (8.7-18)0.01 SAA (μg/mL)1.0 (0.61-1.7)2.3 (1.4-4.5)<0.01 CRP (μg/mL)1.4 (0.61-2.4)5.4 (2.5-12)<0.01 IQR = Inter Quartile Range. Conclusions: The REMIRA LDA cohort is heterogeneous as reflected in the wide range of biomarker concentrations. The MBDA score is capable of differentiating between LDA/remission and LDA/non-remission as defined by DAS28CRP and has a potential role as an assessment tool for disease activity in LDA patients. Longitudinal follow-up of LDA patients may improve our understanding of the relationship between elevated biomarker concentrations and disease progression in patients in whom clinical signs and symptoms of disease are absent. References: 1. Ma MHY et al. J Rheumatol. 2010 Jul;37(7):1444-53. Disclosure of Interest: M. Ma: None Declared, S. Ramanujan Employee of: Crescendo Bioscience, D. Haney Employee of: Crescendo Bioscience, G. Cavet Employee of: Crescendo Bioscience, G. Kingsley: None Declared, D. Scott: None Declared, A. Cope: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 537Session: Cytokines and inflammatory mediators (Poster Presentations )