MONITORING JOINT-SPACE NARROWING IN RHEUMATOID ARTHRITIS WITH 1.5T WHOLE-BODY MRI AND 0.2T EXTREMITY MRI IN A MULTI-SITE CLINICAL TRIAL: IMPRESS

C. Peterfy1, E. Olech2, J. DiCarlo3, J.T. Merrill2, P.J. Countryman1, N. Gaylis4 1Spire Sciences, San Francisco; 2Oklahoma Medical Research Foundation, Oklahoma; 3Synarc, San Francisco; 4Arthritis & Rheumatic Disease Specialties, Aventura, United States

Background: MRI is increasingly being used in clinical trials of rheumatoid arthritis (RA) because of its superiority over X-ray in detecting and monitoring change in bone erosion, osteitis and synovitis. However, in contrast to X-ray, the MRI scoring method most commonly used in clinical trials, RAMRIS1, does not currently include joint-space narrowing (JSN). This limitation has been an obstacle to substituting MRI for X-ray in clinical trials. Cross-sectional studies have shown MRI to be sensitive for JSN in the hands and wrist2,3; although longitudinal sensitivity to change has not yet been confirmed. In this study we monitor change in JSN with 0.2T extremity MRI (E-MRI) and conventional 1.5T whole-body MRI (C-MRI) in a multi-site clinical trial.

Objectives: To examine the abilities of E-MRI and C-MRI to monitor change in JSN in patients with RA in a multi-site clinical trial setting.

Methods: 31 active RA patients from a clinical trial (IMPRESS) who were randomized equally into treatment with either rituximab + methotrexate or placebo + methotrexate had their dominant hand/wrist scanned at baseline, 12 weeks and 24 weeks using C-MRI at 3 clinical sites. 23 of these patients also had E-MRI of the same hand/wrist at each visit. One radiologist [CP] scored all C-MRI images blinded to visit order. The same radiologist similarly read all E-MRI images on a separate occasion blinded to the C-MRI results. JSN was scored in proximal interphalangeal joints (PIP) 1-5, metacarpophalangeal joints1-5 and 15 joints in the wrist (all but carpometacarpal-1, scapholunate, triquetropisiform and radioulnar) using a previously validated 9-point scale2. Data from the two treatment arms were pooled for this analysis. Funding and study drug were provided by F. Hoffmann-La Roche Ltd., Genentech Inc., and Biogen IDEC Pharmaceuticals.

Results: Of 775 joints in the C-MRI group and 575 joints in the E-MRI group, 14% and 7%, respectively, were outside the field of view and could not be assessed. The majority of these were PIP joints. Scores agreed well between the groups (ICC: 0.87-0.94 cross-sectionally and 0.74-0.88 for change). Mean JSN score increased at 12 and 24 weeks (Table). Statistical significance was reached in both groups at 24 weeks. However, when only the 23 patients who had both E-MRI and C-MRI were analyzed, only E-MRI reached statistical significance.

Mean (SD), *p<0.001, †includes 8 pts without matching E-MRI.

Conclusion: To our knowledge, this is the first study to demonstrate MRI's ability to monitor JSN in a multi-site clinical trial. Both E-MRI and C-MRI demonstrated significant progression of JSN in 24 weeks, but only E-MRI reached statistical significance with only 23 patients. This difference may be because E-MRI covered more PIP joints than C-MRI did. These findings suggest that MRI may offer a viable alternative to X-ray in multi-site clinical trials of RA.

References:

• Østergaard M, et al. J Rheumatol 2003;30:1385-6.
• Peterfy C, et al. EULAR 2009.
• Taouli B, et al. Am J Roentgenol 2004;182:937-43

Disclosure of Interest: C. Peterfy Shareholder of: Spire Sciences LLC, Synarc Inc, Consultant for: Abbott, Amgen, Biogen-Idec, Bristol Myers-Squibb, Bioclinica, Celgene, Centocor, Crescendo, Eli Lilly, Genentech, Icon Medical Imaging, Novartis, Pfizer, Rigel, Roche, Synarc, Wyeth, UCB, Employee of: Spire Sciences, E. Olech Grant/Research Support from: Genentech, Consultant for: Genentech, Speakers Bureau: Genentech, J. DiCarlo Employee of: Synarc, J. Merrill Grant/Research Support from: Genentech, Consultant for: Genentech, Paid instructor from: Genentech, P. Countryman Employee of: Spire Sciences, N. Gaylis Grant/Research Support from: Genentech, Consultant for: Genentech

Citation: Ann Rheum Dis 2010;69(Suppl3):460
http://www.abstracts2view.com/eular/view.php?nu=EULAR10L_FRI0446&terms=