MRI Findings Correlate With Clinical Assessments And Biomarkers In Patients With Active Moderate Or Severe Rheumatoid Arthritis

E. Olech1, N. Gaylis2, C. Peterfy3, P.J. Countryman3, A. Genovese1, J. Sagliani2, J. DiCarlo4, G. Valenzuela5, L. Willis6, T. Shaver7, J.T. Merrill1 1Oklahoma Medical Research Foundation, Oklahoma City; 2Arthritis and Rheumatic Disease Specialties, Aventura; 3Spire Sciences; 4Synarc, San Francisco; 5Plantation, FL; 6McBride Clinic, Oklahoma City; 7Arthritis & Rheum Clinics, Wichita, United States

Background: IMPRESS is an ongoing, prospective, double-blind, placebo-controlled study to determine the impact of Rituximab on MRI evidence of synovitis and bone lesions in patients with active, moderate-severe rheumatoid arthritis (RA).
Objectives: To assess correlation of MRI findings with clinical measures and biomarkers potentially associated with different aspects of RA pathology at baseline in patients currently enrolled in the IMPRESS study.
Methods: 42 patients with active RA < 5 years duration, on stable dose of methotrexate (MTX) and exposure to no more than one biologic had 1.5 T MRI of the dominant hand and wrist performed at baseline. The imaging protocol included: hand/wrist coronal 3D T1 GE, coronal STIR, pre- & post-contrast axial 3D T1 of the wrist. Images were scored using the RAMRIS system for erosions, osteitis and synovitis. Joint space narrowing (JSN) was measured using a validated system [1] MRI scores were compared to clinical assessments, ESR, CRP, DAS28, a panel of serum cytokines & chemokines, and cell subsets identified by flow cytometry using Pearson correlation. Funding & study drug were provided by Genentech/Biogen IDEC.
Results: 77% of the patients were female with mean (SD) age of 45.7 (12.6). The mean (SD) RA duration was 21.2 (18.4) months, baseline DAS28 – 6.79 (0.94). Mean MTX dose was 17.1 (2.8), Prednisone 4.1 (4.8); 3 patients were previously exposed to a biologic.
All individual MRI scores significantly correlated with other components of RAMRIS and JSN. MRI-defined synovitis was highly associated with the swollen joint count (SJC), DAS28, CRP and IL6 levels (Table). Blood monocytes are known to be a major source of IL6 [2], which in this study correlated to MRI synovitis but not to osteitis, erosions or JSN. Osteitis, erosions, and JSN score did, however, correlate with serum concentrations of the chemokine RANTES (which may recruit monocytes to the joint [3], but also downregulate IL6 [4]. Osteitis and JSN scores were also associated with counts/50,000 of CD14+/56+ cells (representing a dendritic-like change in the monocyte), as well as with increased percentage of CD14 cells expressing CD56 (%CD14of56+). RANTES levels correlated with CD14+/CD56+ cells and %CD14of56+ (r=0.45/p<0.005 and 0.43/p<0.01 respectively), suggesting the possibility of a causal relationship between this chemokine and the emergence of a monocytoid dendritic cell type in RA as disease progresses from synovitis to joint destruction.

*p<0.01,**p<0.001,***p<0.0001.

Conclusion: MRI may contribute valuable information on the RA disease activity, stage, sub-type and eventually help guide treatment.
References:
• Peterfy C, et al. EULAR 2009
• Almeida J, et al. Clin Immunol 2001
• Swaak AJ, et al. Ann Rheum Dis 1997
• Shahrara S, et al. J Immunol 2006
Disclosure of Interest: E. Olech Grant/Research Support from: Genentech, Consultant for: Genentech, Speakers Bureau: Genentech, N. Gaylis Grant/Research Support from: Genentech, Consultant for: Genentech, Speakers Bureau: Genentech, C. Peterfy Shareholder of: Spire Sciences, Synarc, Consultant for: Abbott, Amgen, Biogen-Idec, Bristol Myers-Squibb, Bioclinica, Celgene, Centocor, Crescendo, Eli Lilly, Genentech, Icon Medical Imaging, Novartis, Pfizer, Rigel, Roche, Synarc, UCB, Wyeth, Employee of: Spire Sciences, P. Countryman Employee of: Spire Sciences, A. Genovese: None Declared, J. Sagliani: None Declared, J. DiCarlo Employee of: Synarc, G. Valenzuela Grant/Research Support from: Genentech, L. Willis Grant/Research Support from: Genentech, Consultant for: Genentech, T. Shaver Grant/Research Support from: Genentech, J. Merrill Grant/Research Support from: Genentech, Consultant for: Genentech, Paid instructor from: Genentech

Citation: Ann Rheum Dis 2010;69(Suppl3):118
http://www.abstracts2view.com/eular/view.php?nu=EULAR10L_OP0190