MRI comes of age in RA clinical trials

Abstract

The success of modern rheumatoid arthritis (RA) therapies and treatment strategies has led to extended placebo phases being unethical in RA randomised controlled trials (RCTs). Modern trials therefore increasingly involve active comparator designs, and this together with some technical issues has meant difficulties in differentiating structural progression using traditional radiographic outcome measures. Magnetic resonance imaging (MRI) has been demonstrated to assess damage more sensitively than radiographs, but importantly it can measure the upstream drivers of erosions and cartilage loss, synovitis and osteitis. An increasing number of recent RCTs using the RA MRI scoring system (RAMRIS) have demonstrated the ability of MRI to discriminate progression and treatment effect. Consistency of erosion progression determination was seen across the majority of these studies. In most studies, MRI demonstrated reduction in synovitis and osteitis at early (12 week) timepoints, and MRI predicted subsequent radiographic findings. Often small numbers of patients were required to demonstrate such changes. The time is right for regulatory authorities to include MRI as an alternative to radiographic data in support of claims of inhibition of progression of structural damage in RA trials.

The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy

“…Some studies have demonstrated that 30% of patients in remission had radiographic progression, 96% had synovitis and 35% had osteitis 6 7. MRI therefore enables a more sensitive assessment of disease activity, detection of early markers of disease progression and provides a sensitive measure of therapeutic response 8 9…”

A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis: results from the OPERA randomised controlled trial

“…However, the optimal treatment strategy of patients with early RA (ERA), including choices such as initial monotherapy versus combination therapy, and the role of glucocorticosteroids and biological agents has still not been settled 2 3. Trials including active comparators rather than a traditional placebo arm, require sensitive outcome measures to be able to distinguish reliably between therapeutic strategies 4 5…”

Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

“…MRI has demonstrated criterion validity for osteitis and synovitis with histology and construct validity for erosions when compared with CT 3 4. Numerous studies have demonstrated MRI to be more sensitive than X-ray in detecting joint damage and to detect synovitis and osteitis more sensitively than clinical examination does.…”