Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring

PLoS One. 2017 Dec 13;12(12):e0187397. doi: 10.1371/journal.pone.0187397. eCollection 2017.


The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI. In addition to clinical assessments with DAS28(CRP), the severity of inflammation was measured as synovial leak of gadolinium based contrast agent (GBCA) using DCE-MRI (Ktrans, primary endpoint) at weeks 0, 2, 4, and 14. Two radiologists independently scored synovitis, osteitis and erosion using RA MRI Score (RAMRIS) and cartilage loss using a 9-point MRI scale (CARLOS). Infliximab showed greater decrease from baseline in DAS28(CRP), DCE-MRI Ktrans of wrist and MCP synovium, and RAMRIS synovitis and osteitis at all visits compared with placebo (p<0.001). Treatment effect sizes of infliximab therapy were similar for DAS28(CRP) (1.08; 90% CI (0.63-1.53)) and MRI inflammation endpoints: wrist Ktrans (1.00 (0.55-1.45)), RAMRIS synovitis (0.85 (0.38-1.28)) and RAMRIS osteitis (0.99 (0.52-1.43)). Damage measures of bone erosion (RAMRIS) and cartilage loss (CARLOS) were reduced with infliximab compared to with placebo at 14 weeks (p≤0.025). DCE-MRI and RAMRIS were equally sensitive and responsive to the anti-inflammatory effects of infliximab. RAMRIS and CARLOS showed suppression of erosion and cartilage loss, respectively, at 14 weeks. ( registration: NCT01313520).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnostic imaging*
  • Arthritis, Rheumatoid / drug therapy*
  • Contrast Media*
  • Double-Blind Method
  • Female
  • Gadolinium / administration & dosage
  • Hand / diagnostic imaging*
  • Humans
  • Infliximab / therapeutic use*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Placebos
  • Treatment Outcome
  • Wrist / diagnostic imaging*


  • Antirheumatic Agents
  • Contrast Media
  • Placebos
  • Gadolinium
  • Infliximab

Associated data


Grant support

This research was funded by Merck & Co., Inc., Kenilworth, NJ, including the provision of infliximab. All authors, including Merck employees, participated in interpretation of data, writing or review of the manuscript, as well as the decision to submit the manuscript for publication. The funder provided support in the form of salaries for authors CB, RB, AC, DF, M-HV, BD and funded the analysis by contract companies [Spire Sciences/Virtual Scopics], but did not have any additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Spire Sciences, Inc., provided support in the form of salaries for authors CP and JD and VirtualScopics provided support in the form of salary for author EA, but these companies did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.