Repeatability and response to therapy of dynamic contrast-enhanced Magnetic Resonance Imaging biomarkers in rheumatoid arthritis in a large multicentre trial setting.
Objectives To determine the repeatability, and response to therapy, of Dynamic Contrast-Enhanced (DCE) MRI biomarkers of synovitis in hand and wrist of Rheumatoid Arthritis (RA) patients, and in particular the performance of the transfer constant Ktrans, in a multicentre trial setting Methods DCE-MRI and RA MRI scoring (RAMRIS) were performed with meticulous standardisation at baseline, 6 and 24 weeks in a sub-study of fostamatinib monotherapy in reducing synovitis compared with placebo or adalimumab. Analysis employed statistical shape modelling to avoid biased regions-of-interest, kinetic modelling and heuristic analyses. Repeatability was also evaluated. Results At early study termination, DCE-MRI data had been acquired from 58 patients in 19 imaging centres. Ktrans intra-subject coefficient of variation (N=14) was 30%. Ktrans change demonstrated inferiority of fostamatinib (N=11) relative to adalimumab (N=10) after 6 weeks (treatment ratio=1.92, p=0.003), and failed to distinguish fostamatinib from placebo (N=10, p=0.79). RAMRIS showed superiority of fostamatinib relative to placebo at 6 weeks (p=0.023), and did not distinguish fostamatinib from adalimumab at either 6 weeks (p=0.175) or 24 weeks (p=0.230). Conclusion This demonstrated repeatability of Ktrans, and its ability to distinguish treatment groups, show that DCE-MRI biomarkers are suitable for use in multicentre RA trials.</p
