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.

Chan Beals,Edward Ashton,Marie-Helene Vallee,Dai Feng,Bernard J Dardzinski,Richard Baumgartner,Charles Peterfy,Julie Dicarlo,Andra Balanescu,Amy Cheng,Gavrila Mirea,Serghei Popa,Alexandru Harabagiu,Xiaojuan Li

doi:10.1371/journal.pone.0187397

Abstract

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. (ClinicalTrials.gov registration: NCT01313520)

Highlights

Rheumatoid arthritis (RA) treatment options have expanded markedly over the past decade
Dynamic contrast enhanced MRI (DCE-MRI) is a quantitative method for assessing synovitis based on the rate and magnitude of enhancement of synovial tissue by intravenously administered gadolinium-based contrast agents (GBCAs) [4,5,6,7,8,9]
DCE-MRI Ktrans and RA MRI Score (RAMRIS) synovitis and osteitis showed stable disease activity with placebo treatment, and each measure had a treatment effect size with infliximab that was quantitatively similar to the DAS28(CRP) benchmark

Summary

Introduction

Rheumatoid arthritis (RA) treatment options have expanded markedly over the past decade. As these therapies have become available, the acceptable duration for placebo control has shortened, with rescue therapy typically offered within 14–16 weeks. MRI has been shown to be more sensitive than radiography for detecting joint destruction in RA, and uniquely able to evaluate the up-stream inflammatory drivers of bone erosion and articular cartilage loss, namely osteitis and synovitis. The most widely used method for monitoring bone erosion, osteitis and synovitis with MRI in RA clinical trials is RAMRIS (RA MRI Score), developed by OMERACT (Outcome Measures in Rheumatology) more than a decade ago[2]. The most widely used MRI method for evaluating cartilage loss in RA trials is the 9-point cartilage score (CARLOS) developed by Peterfy et al[3]. DCE-MRI is more difficult to perform than is conventional contrastenhanced MRI, upon which RAMRIS assessments are based, and unlike RAMRIS and CARLOS,[10] successful use of DCE-MRI based measures in multicenter RA trials has yet to be reported

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