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 the 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 and 6 and 24 weeks in a substudy 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 (p = 0.175) or 24 (p = 0.230) weeks.

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.