Monitoring cartilage loss in the hands and wrists in rheumatoid arthritis with magnetic resonance imaging in a multi-center clinical trial: IMPRESS (NCT00425932)

Abstract

Introduction: Magnetic resonance imaging (MRI) is increasingly being used in clinical trials of rheumatoid arthritis (RA) because of its superiority over x-ray radiography (XR) in detecting and monitoring change in bone erosion, osteitis and synovitis. However, in contrast to XR, the MRI scoring method that was used in most clinical trials did not include cartilage loss. This limitation has been an obstacle to accepting MRI as a potential alternative to XR in clinical trials. Cross-sectional studies have shown MRI to be sensitive for cartilage loss in the hands and wrist; although, longitudinal sensitivity to change has not yet been confirmed. In this study we examined the ability of MRI to monitor change in cartilage loss in patients with RA in a multi-site clinical trial setting.

Methods: Thirty-one active RA patients from a clinical trial (IMPRESS) who were randomized equally into treatment with either rituximab + methotrexate or placebo + methotrexate had MRI of the dominant hand/wrist at baseline, 12 weeks and 24 weeks at 3 clinical sites in the US. Twenty-seven of these patients also had XR of both hands/wrists and both feet at baseline and 24 weeks. One radiologist scored all XR images using the van der Heijde-modified Sharp method blinded to visit order. The same radiologist scored MR images for cartilage loss using a previously validated 9-point scale, and bone erosion using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI Score (RAMRIS) blinded to visit order and XR scores. Data from the two treatment arms were pooled for this analysis.

Results: Mean MRI cartilage score increased at 12 and 24 weeks, and reached statistical significance at 24 weeks. XR total Sharp score, XR erosion score and XR joint-space narrowing (JSN) score all increased at 24 weeks, but only XR total Sharp score increased significantly.

Conclusions: To our knowledge, this is the first publication of a study demonstrating MRI's ability to monitor cartilage loss in a multi-site clinical trial. Combined with MRI's established performance in monitoring bone erosions in RA, these findings suggest that MRI may offer a superior alternative to XR in multi-site clinical trials of RA.

Trial registration: ClinicalTrials.gov NCT00425932.

Figures

Figure 1

Positioning device used for reproducible alignment of the bones and joints of the hand and wrist during serial magnetic resonance imaging. (A) Hand and wrist are shown positioned on the acrylic M-frame™ with the fingers and thumb adducted and in plane with each other. (B) The hand and wrist are secured to the frame with self-adhesive, latex-free, elastic bandage (images courtesy of Spire Sciences, Inc).

Figure 2

Positioning of surface coil for magnetic resonance imaging of metacarpophalangeal and proximal interphalangeal joints (A) and wrist joints (B). Because of limited field of view of surface coils available at the sites acquiring images for this study, two separate scans (A, B) were required to cover the hand and wrist completely.

Figure 3

Locations evaluated for cartilage loss and bone erosion with magnetic resonance imaging. (A) Cartilage loss was scored in proximal interphalangeal joints 1 to 5, metacarpophalangeal joints (MCP) 1 to 5, and 15 joints in the wrist. (B) Bone erosion was scored in the 10 bones of MCP 1-5 and all 15 bones of the wrist.

Figure 4

Progression of joint damage in the radiolunate joint. Magnetic resonance imaging (MRI) of the wrist shows thin but present high-signal-intensity cartilage over articular surfaces of the radiolunate joint (large arrow) at baseline (A) associated with grade-1.0 cartilage thinning. Corresponding baseline conventional radiography (XR) (D) shows joint-space narrowing (JSN) at this location (large arrow). Follow-up MRI at 12 weeks (B) and 24 weeks (C) show progressive JSN associated with loss of cartilage over both articular surfaces of this joint, indicative of grade-3.0 cartilage loss. Note development and progression of bone erosions (small arrows) in the radius and lunate on these follow-up scans. Week-24 XR also shows complete radiolunate JSN, the lunate erosion and two of the radius erosions (small arrows). However, the third erosion in the radius is not visible on XR.

Figure 5

Assessing cartilage directly is more accurate than measuring joint-space width. Intact articular cartilage can be seen in these magnetic resonance images of the wrist as bands of high-signal-intensity tissue lining the surfaces of the bones and showing sharp contrast with low-signal-intensity joint fluid along the articular surfaces, and very low-signal-intensity bone cortex and suppressed marrow fat along the subchondral surfaces. Follow-up image (B) shows narrowing of the radioscaphoid joint space (arrows) relative to that in image (A). However, this narrowing is the result of displacement of joint fluid from between the intact articular cartilage surfaces because of abduction of the wrist rather than because of thinning of the cartilage plates themselves. Thus, joint-space width can be an inaccurate measure of cartilage thickness.

Figure 6

Oblique radiographic projection can simulate joint-space narrowing on conventional radiography (XR). (A) Metacarpophalangeal joint (MCP)-1 joint space (short arrow) appears narrowed due to oblique projection on XR. (B) Magnetic resonance imaging of the same MCP joint shows intact articular cartilage and normal joint-space width (long arrow).

Figure 7

Mean change in magnetic resonance imaging (MRI) scores (one hand per patient) from baseline. *P <0.05.

Figure 8

Mean change in conventional radiography (XR) scores (two hands, wrists, feet per patient) from baseline. *P <0.05.