RESEARCH - MRI bone edema is the strongest predictor of subsequent radiographic progression in early RA - CIMESTRA

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Ann Rheum Dis. Published Online First: 3 April 2008. doi:10.1136/ard.2008.088245

Copyright © 2008 BMJ Publishing Group Ltd & European League Against

Rheumatism

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Extended Report

MRI bone oedema is the strongest predictor of subsequent radiographic

progression in early rheumatoid arthritis. Results from a 2 year

randomized controlled trial (CIMESTRA)

Merete Lund Hetland 1*, Bo Jannik Ejbjerg 2, Kim Hørslev-sen 3,

Søren sen 4, Aage Vestergaard 2, Anne Grethe Jurik 5, Kristian

Stengaard-Pedersen 5, Junker 6, Tine Lottenburger 6, Ib Hansen

5, Lis Smedegaard Andersen 6, Ulrik Tarp 5, Henrik Skjødt 2, Jens K

Pedersen 6, Ole Majgaard 2, Anders J Svendsen 6, Torkell Ellingsen 5,

Hanne M Lindegaard 6, Anne F Christensen 6, Jørgen Vallø 7, Trine

Torfing 6, Eva Narvestad 2, Henrik S Thomsen 8 and Mikkel stergaard 2

1 H:S Hvidovre Hospital, Denmark

2 Copenhagen University Hospital at Hvidovre, Denmark

3 King CHristian X's Rheumatology Hospital, Denmark

4 Rigshospitalet, University of Copenhagen, Denmark

5 Århus University Hospital, Denmark

6 University of Southern Denmark, Denmark

7 Aabenraa Sygehus, Denmark

8 Copenhagen University Hospital at Herlev, Denmark

Abstract

Objective: To identify predictors of radiographic progression in a

2-year randomized, double-blind clinical study (CIMESTRA) of patients

with early rheumatoid arthritis (RA).

Methods: Early RA patients (N=130) were treated with methotrexate,

intra-articular betamethasone and cyclosporine/placebo-cyclosporine.

Baseline magnetic resonance imaging (MRI) of the wrist

(wrist-only-group:N=130) or MRI of wrist and MCP-joints

(wrist+MCP-group:N=89) (OMERACT RAMRIS), x-rays of hands, wrists and

forefeet (Sharp/vdHeijde Score (TSS)), disease activity score (DAS28),

anti-cyclic-citrullinated-peptide-antibodies (anti-CCP),

HLA-DRB1-shared-epitope (SE) and smoking status were assessed.

Multiple regression analysis was performed with delta-TSS (0-2 years)

as dependent variable, and baseline DAS28, TSS, MRI bone oedema score,

MRI synovitis score, MRI erosion score, anti-CCP, smoking, SE, age and

gender as explanatory variables.

Results: Baseline values: median DAS28: 5.6 (range: 2.4-8.0); anti-CCP

positive: 61%; radiographic erosions: 56%. At 2 years: DAS28: 2.0

(0.5-5.7), in DAS-remission: 56%, radiographic progression: 26%

(wrist+MCP-group, similar for wrist-only-group). MRI bone oedema score

was the only independent predictor of delta-TSS (wrist+MCP-group:

coefficient=0.75 (95%CI: 0.56-0.97), p<0.00001; wrist-only-group:

coefficient=0.56 (0.41-0.77), p<0.00001). Bone oedema score explained

41% of the variation in the progression of TSS (wrist+MCP-group), 25%

in wrist-only-group, (Pearson's r=0.64 and r=0.50, respectively). The

results were confirmed by sensitivity analyses.

Conclusion: In a RCT aiming at remission in early RA patients,

baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of

wrist only) was the strongest independent predictor of radiographic

progression in hands, wrists and forefeet after 2 years. MRI synovitis

score, MRI erosion score, DAS28, anti-CCP, SE, smoking, age and gender

were not independent risk factors.

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