Assessing whole body synovial inflammation as a predictor of flare when tapering therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory condition affecting the joints which, if untreated, can result in progressive joint damage and disability. Recent data suggests that once RA is under control the treatment (therapy) may be reduced (tapered).

However, as therapy is reduced or removed, a significant proportion of patients will flare requiring reintroduction of therapy.

Deciding when and how to reduce therapy is a significant challenge as low-level inflammation may persist even when there are no symptoms.

Existing measures (e.g. the disease activity score DAS-28) are insufficient as some patients in clinical remission will still flare.

Current imaging techniques (e.g. ultrasound) take significant time, are operator dependent, and do not support assessment of disease activity at the whole patient level.

We have pioneered a new method of detecting active synovial inflammation which has the potential to detect subclinical inflammation. This utilises a radiolabelled tracer, 99mTc-maraciclatide, which can highlight actively inflamed joints.

We performed two studies in a total of 55 patients with active RA where we compared the new imaging technique with ultrasound (US) and found very close correlation at the whole-body level.

We will investigate whether baseline tracer activity, as a measure of whole-body synovial inflammatory load, is predictive of flare when tapering therapy.

The imaging requires only the standard equipment already widely available in all hospitals with a nuclear imaging department, and hence this new technique would not require new investment in resources or expertise.

This technology can image joint inflammation at the whole-body level, giving and overall measure of inflammatory load, with significant practical advantages compared to US which are not operator dependent.

Whole-body scans, including more detailed images of the hands and feet, can be acquired in ~30 minutes which is significantly shorter than US.

This study, in collaboration with industry partners, aims to explore assessment of whole body synovial inflammatory activity as a predictor of disease flare in patients whose treatment is being tapered.

RA patients who have already been assessed as suitable for therapy tapering will be imaged twice during therapy tapering, once at baseline and again after 12 weeks. Patients will continue therapy tapering according to local protocols, and be monitored over the following 12 months.

After 12 months an analysis will be performed to determine if the scans, individually or sequentially, predict which patients can safely be tapered and which cannot.

If successful, this work could provide the basis for stratified tapering i.e. continuing therapy in those at high risk of flare, while tapering only those at low risk.

The overall aim is to prevent return of symptoms and the risk of progressive joint damage, and thus optimise patient outcomes.

This approach could lead to fewer unnecessary disease flares and less unnecessary treatment, providing a way to confidently reduce medication burden and exposure to the risk of immunosuppression as well as improving cost-effectiveness of treatment and patient outcomes.

This project will be conducted in two centres affiliated to the UK Musculoskeletal Translational Research Collaboration, Guy's and St Thomas' BRC and Leeds BRC