Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial delivery (RAPPORT).

Our ambition is to deliver a pan-European precision medicine platform for preventative interventions in people at risk of rheumatoid arthritis (RA) – a disease of immune dysregulation in which destructive joint inflammation impairs quality of life. Current management aimed at long-term suppression of inflammation incurs unwanted effects and sustained financial cost.

However, ever-advancing understanding of RA pathogenesis, during which symptoms may accompany latent autoimmunity in people at risk of the condition – together with emergent biomarkers of relevance for quantifying that risk and an array of targeted therapies – all suggest disease prevention is now within reach.

Isolated trials of time-limited interventions have addressed this possibility and shown promise, but progress is hampered by recruitment challenges and inconsistent enrolment criteria.

A coordinated, multicentre strategy to deliver interventional trials efficiently and responsively in suitably characterised populations of at-risk volunteers therefore remains a major unmet need.

Leveraging a recently-established Europe-wide registry of people at risk of RA (European Risk RA Registry) together the UK NIHR Musculoskeletal Translational Research Collaboration (TRC), and building on an existing international network of clinician scientists in the field (RT-Cure and NORMALISE Consortia), our aim is to bring about a step-change in progress towards RA prevention by launching a platform trial whose sequential readouts accelerate new knowledge and directly inform precision medicine guidelines for the clinic.

During a 12-month Accelerator Project we will first convene an international At Risk RA Precision Platform Trial Management Group (TMG) with representation from expert UK/EU units, individuals with experience of living at risk of RA and the Risk RA Registry to plan coordinated participant identification, enrolment and follow-up that builds on existing infrastructure.

Having refined and achieved consensus on optimal clinical and immunological biomarkers (including cut-offs and implementation strategies) for participant stratification in a precision medicine platform, we will next design and establish a Master Protocol compatible with the range of healthcare infrastructures of countries in which it is to be deployed.

Recognising challenges to delivery, this will be informed by systematic literature review and expert sponsorship, information governance and contracting teams at Newcastle Hospitals NHS Foundation Trust (NuTH).

In parallel we will engage existing industry/academic partners to finalise initiator interventional arms and feasibility, supported by robust power calculations based on real-life data.

Further supported by local and international PPI/E groups, our collaboration with NuTH and Newcastle Clinical Trials Unit (NCTU) paves the way for a UK-led funding application to launch our international precision medicine platform study in April 2024.

Successful delivery will herald a coordinated strategy to prevent RA and, by extension, other immune-mediated inflammatory diseases (IMIDs).