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Six-month prospective trial in early and long-standing rheumatoid arthritis: evaluating disease activity in the wrist through sequential synovial histopathological analysis, RAMRIS magnetic resonance score and EULAR-OMERACT ultrasound score
  1. Søren Andreas Just1,2,
  2. Christian Nielsen3,4,
  3. Jens Christian Werlinrud5,
  4. Pia Veldt Larsen6,
  5. Camilla Schufri Klinkby1,
  6. Henrik Daa Schrøder7,
  7. Fran Humby8,
  8. Trine Torfing9 and
  9. Hanne Lindegaard1
  1. 1Department of Rheumatology, Odense University Hospital, Odense, Denmark
  2. 2Section of Rheumatology, Department of Medicine, Svendborg Sygehus OUH, Svendborg, Denmark
  3. 3Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
  4. 4Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark
  5. 5Department of Orthopaedic Surgery, Odense Universiy Hospital, Odense, Denmark
  6. 6Department of Epidemiology and Biostatistics, University of Southern Denmark, Odense, Denmark
  7. 7Department of Pathology, Odense University Hospital, Odense, Denmark
  8. 8Centre for Experimental Medicine and Rheumatology, Barts and the London School of Medicine and Dentistry, London, UK
  9. 9Section of musculoskeletal radiology, Department of Radiology, Odense University Hospital, Odense, Denmark
  1. Correspondence to Dr Søren Andreas Just,Department of Rheumatology, Odense Universitetshospital, Odense, Denmark; soeren.andreas.just{at}


Introduction Standardised scoring systems for rheumatoid arthritis (RA) joint disease activity include Larsen score for radiographs, rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for MRI and using the European League Against Rheumatisms-Outcome Measures in Rheumatology (EULAR-OMERACT) score for ultrasound (US) images. The aim of this prospective study was to investigate the relationship between histological synovitis and radiological synovitis, assessed by conventional X-ray, US and MRI of the wrist radiocarpal joint.

Methods 20 patients with treatment naive early RA (ERA) and 20 with long-standing RA (LRA) were enrolled in a 6-month prospective study. Patients with RA underwent US-guided synovial biopsy, X-ray and US of the wrist at enrolment and 6 months. MRI at baseline and also at 6 months for the ERA group, and scored with the RAMRIS system. X-ray was scored by Larsen score and US by the EULAR-OMERACT system. Synovial biopsy inflammation was determined by the Krenn score.

Results In the ERA group at baseline, Krenn score was correlated strongly with both US combined score (r = 0.77 p < 0.001) and MRI synovitis score (r = 0.85 p < 0.001), while uncorrelated at 6 months. In the LRA group at baseline, these scores correlated strongly (r = 0.83, p < 0.001) to moderately (r = 0.61, p = 0.002), and persisted at 6 months for US score (r = 0.81 p < 0.001). For all patients with RA, change in Krenn score between baseline and 6 months was correlated with both change in US combined score (r = 0.65, p < 0.001) and change in MRI synovitis score (r = 0.50, p = 0.03).

Conclusion The MRI RAMRIS synovitis score and EULAR-OMERACT US scoring system are sensitive measures of histological synovitis in LRA and ERA. After 6 months, this correlation persists in the established RA group, but not in the ERA group. Overall, decreases in MRI/US synovitis are associated with reductions in histological synovitis. The study validates the use of MRI RAMRIS and EULAR-OMERACT US scores as surrogate markers of histological synovitis in established RA and early untreated RA.

  • rheumatoid arthritis
  • imaging
  • EULAR-OMERACT ultrasound score
  • ultrasound-guided synovial biopsies
  • synovial pathotypes

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  • Contributors All authors have contributed substantially in the process of completing this study, specified as follows: Conception of the study: SAJ. Designing the study: SAJ and HL. Aggregation of data: SAJ and HL. Statistics: SAJ and PVL. Interpretation of data: All authors. Drafting and revising, final approval and agreement to be accountable: All authors.

  • Funding SAJ is supported by grants from The Danish Rheumatism Association and Odense University Hospital PhD Fund and Fund for clinical research.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Denmark, Odense: The SynRA study is approved by the regional ethics review board (S-20140062) and the Danish Data Protection Agency (2008-58-0035).

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

  • Data availability statement Data are available upon reasonable request.

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