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Extended report
Biomarkers in early rheumatoid arthritis: longitudinal associations with inflammation and joint destruction measured by magnetic resonance imaging and conventional radiographs
  1. Silje W Syversen1,
  2. Espen A Haavardsholm1,
  3. Pernille Bøyesen1,
  4. Guro L Goll1,
  5. Cecilie Okkenhaug1,
  6. Per Ivar Gaarder2,
  7. Désirée van der Heijde1,3,
  8. Tore K Kvien1
  1. 1Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  2. 2Department of Immunology and Transfusion Medicine, University Hospital Ullevål, Oslo, Norway
  3. 3Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
  1. Correspondence to Dr Silje W Syversen, Department of Rheumatology, Diakonhjemmet Hospital, PB 23 Vindern, N-0319 Oslo, Norway; s.w.syversen{at}


Objective To examine associations between a panel of soluble biomarkers and progressive joint destruction assessed by magnetic resonance imaging (MRI) and conventional radiographs as well as longitudinal associations with disease activity assessed clinically and by MRI in early rheumatoid arthritis (RA) patients.

Methods 84 early RA patients were evaluated at baseline, 3, 6 and 12 months with clinical examination, serum and urine sampling, MRI scans of the dominant wrist and conventional radiographs of the hands. A panel of biomarkers (sCTX-I, uCTX-II, sOPG, sYKL-40, sCOMP and sMMP-3) was assessed by ELISA. MRI images and conventional radiographs were scored according to the RA MRI score (RAMRIS) and the van der Heijde modified Sharp score (SHS), respectively. Longitudinal associations between biomarkers and MRI inflammation and disease activity score (DAS28) and association with the progression of damage were examined with adjustments for known predictors.

Results The baseline sCTX-I level predicted progression in joint destruction assessed by MRI and conventional radiographs, whereas the uCTX-II level was a predictor of progression in SHS but not RAMRIS. Consistent associations, both with MRI inflammation (synovitis and bone marrow oedema) and DAS28 were found for sYKL-40 and sMMP-3 in addition to C-reactive protein at baseline and in longitudinal analyses. Associations remained significant in multivariate analyses.

Conclusion Levels of sCTX-I and uCTX-II were significant predictors of progressive joint destruction, whereas sMMP-3 and sYKL-40 were merely markers of joint inflammation. The clinical value of these markers for use in individual patients is limited due to a considerable overlap in levels of patients with progression and no progression.

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  • Funding This study has been financed with grants from the Eastern Norway Regional Health Authority, grants from the Research Council of Norway, the Norwegian Rheumatism Association, the Norwegian Women Public Health Association and Grethe Harbitz Legacy.

  • Competing interests None. Hans Bijlsma was the Handling Editor.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Regional Ethics Committee, Eastern Norway.

  • Provenance and peer review Not commissioned; externally peer reviewed.