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-Petersen ³, Søren Jacobsen ⁴, Aage Vestergaard ², Anne Grethe Jurik ⁵, Kristian Stengaard-Pedersen ⁵, Peter 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

^* To whom correspondence should be addressed. E-mail: merete.hetland{at}dadlnet.dk.

Accepted 24 March 2008

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.