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MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2 year randomized controlled trial (CIMESTRA)
  1. Merete Lund Hetland (merete.hetland{at}dadlnet.dk)
  1. H:S Hvidovre Hospital, Denmark
    1. Bo Jannik Ejbjerg (ejbjerg{at}dadlnet.dk)
    1. Copenhagen University Hospital at Hvidovre, Denmark
      1. Kim Hørslev-Petersen (khorslevpetersen{at}gigtforeningen.dk)
      1. King CHristian X's Rheumatology Hospital, Denmark
        1. Søren Jacobsen (sj{at}dadlnet.dk)
        1. Rigshospitalet, University of Copenhagen, Denmark
          1. Aage Vestergaard (aage.vestergaard{at}hvh.regionh.dk)
          1. Copenhagen University Hospital at Hvidovre, Denmark
            1. Anne Grethe Jurik (jurik{at}dadlnet.dk)
            1. Århus University Hospital, Denmark
              1. Kristian Stengaard-Pedersen (stengaard{at}rheum.dk)
              1. Århus University Hospital, Denmark
                1. Peter Junker (peter.junker{at}ouh.regionsyddanmark.dk)
                1. University of Southern Denmark, Denmark
                  1. Tine Lottenburger (tine.lottenburger{at}get2net.dk)
                  1. University of Southern Denmark, Denmark
                    1. Ib Hansen (ibhansen{at}dadlnet.dk)
                    1. Århus University Hospital, Denmark
                      1. Lis Smedegaard Andersen (lsandersen{at}dadlnet.dk)
                      1. University of Southern Denmark, Denmark
                        1. Ulrik Tarp (ulrik.tarp{at}dadlnet.dk)
                        1. Århus University Hospital, Denmark
                          1. Henrik Skjødt (hskj{at}dadlnet.dk)
                          1. Copenhagen University Hospital at Hvidovre, Denmark
                            1. Jens K Pedersen (jensk{at}dadlnet.dk)
                            1. University of Southern Denmark, Denmark
                              1. Ole Majgaard (suolm{at}stam.dk)
                              1. Copenhagen University Hospital at Hvidovre, Denmark
                                1. Anders J Svendsen (asvendsen{at}health.sdu.dk)
                                1. University of Southern Denmark, Denmark
                                  1. Torkell Ellingsen (torkell{at}dadlnet.dk)
                                  1. Århus University Hospital, Denmark
                                    1. Hanne M Lindegaard (lindegaard{at}dadlnet.dk)
                                    1. University of Southern Denmark, Denmark
                                      1. Anne F Christensen (anne.friesgaard.christensen{at}ouh.regionsyddanmark.dk)
                                      1. University of Southern Denmark, Denmark
                                        1. Jørgen Vallø (valloe{at}dadlnet.dk)
                                        1. Aabenraa Sygehus, Denmark
                                          1. Trine Torfing (t.torfing{at}dadlnet.dk)
                                          1. University of Southern Denmark, Denmark
                                            1. Eva Narvestad (eva.narvestad{at}rh.regionh.dk)
                                            1. Copenhagen University Hospital at Hvidovre, Denmark
                                              1. Henrik S Thomsen (heth{at}heh.regionh.dk)
                                              1. Copenhagen University Hospital at Herlev, Denmark
                                                1. Mikkel Østergaard (mo{at}dadlnet.dk)
                                                1. Copenhagen University Hospital at Hvidovre, 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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