For the first time, a validated, internationally agreed framework now exists for identifying individuals at high risk of developing rheumatoid arthritis before clinical arthritis is apparent. This landmark EULAR/ACR initiative could transform how RA is detected, researched and — eventually — prevented.
- RA develops through a pre-clinical phase lasting months or years — new EULAR/ACR criteria can now identify people in this at-risk window
- Six practical clinical predictors — including morning stiffness, ACPA positivity and elevated CRP — form the core of the risk score (AUC 0.80)
- Adding MRI findings dramatically improves predictive accuracy to AUC 0.93, with MRI tenosynovitis identified as a key early marker
- These criteria are currently intended for research use and prevention trials, not routine clinical decision-making — but they represent a major step towards RA prevention
Why This Development Matters
For decades, rheumatologists have diagnosed rheumatoid arthritis only after inflammatory arthritis becomes clinically apparent — visible swelling, tenderness, reduced range of movement. By that stage, immune-mediated joint inflammation may already have caused irreversible structural damage to cartilage and bone.
Research has shown that autoantibodies, immune abnormalities and characteristic prodromal symptoms can be detected months or even years before clinical arthritis develops. Increasingly, rheumatologists have been focusing on this “pre-RA” phase, where earlier intervention might modify disease progression — or potentially prevent the onset of established arthritis altogether [1].
Recent clinical trials — including APIPPRA, ARIAA and TREAT EARLIER — have demonstrated that treatment during this at-risk phase can indeed influence disease trajectories. However, a critical obstacle has persisted: the absence of a validated, internationally agreed method for identifying who is genuinely at high risk of progression. Without such a framework, prevention trials have been difficult to design, patient selection has been inconsistent, and regulatory approval of preventive strategies has remained out of reach.
This new 2025 EULAR/ACR initiative directly addresses that gap.
The Study: Design and Population
Investigators pooled data from 10 international cohorts involving 2,293 individuals with arthralgia considered to be at risk of RA. Participants either had clinically suspect arthralgia (CSA) — joint pain with features suggesting possible future RA — or autoantibody-positive arthralgia, where serological markers of autoimmunity were already present without clinical arthritis.
Researchers systematically analysed which baseline clinical, serological and imaging factors best predicted progression to inflammatory arthritis within one year, then developed and validated a simplified scoring system based on the strongest independent predictors.
The Six Key Clinical Predictors
The strongest predictors identified were remarkably practical — readily available in any routine rheumatology consultation without specialist equipment:
- Morning stiffness
- Patient-reported joint swelling
- Difficulty making a fist
- Elevated C-reactive protein (CRP)
- Rheumatoid factor (RF) positivity
- Anti-citrullinated peptide antibodies (ACPA) positivity
Together, these six variables achieved excellent predictive performance with an area under the curve (AUC) of 0.80. Of all variables assessed, ACPA positivity was the single strongest predictor of future RA — particularly when present at high titre — confirming its established role as an early pathological marker of the RA disease process [2].
The Role of Imaging: Ultrasound and MRI
The investigators went beyond clinical and serological factors to evaluate whether imaging for subclinical inflammation could further improve risk prediction.
Ultrasound
Ultrasound detected several abnormalities predictive of future RA, including power Doppler synovitis, tenosynovitis and metatarsophalangeal (MTP) joint inflammation. However, adding ultrasound findings did not significantly improve the overall predictive performance of the clinical and serological model — a finding that challenges the assumption that ultrasound should be routine in at-risk assessment and has important implications for clinical workflow.
MRI
MRI told a substantially different story. MRI-detected tenosynovitis and inflammatory changes markedly improved prediction accuracy:
- AUC increased from 0.80 to 0.87 with clinical MRI findings added
- Sensitivity and specificity both approached 80%
- When used for RA-specific prediction, the AUC reached 0.93
The most informative MRI findings were flexor wrist tenosynovitis, extensor wrist tenosynovitis, extensor MCP tenosynovitis and extensor MTP tenosynovitis. This reinforces a growing body of evidence that tendon inflammation — not just synovitis — may be one of the earliest detectable manifestations of impending RA, and that MRI has a meaningful role in risk stratification where clinical uncertainty remains.
The New EULAR/ACR Risk Score
The final simplified scoring system draws on the six clinical and serological factors, with MRI findings added for greater precision where available.
Clinical and Serological Scoring
| Variable | Points |
|---|---|
| Morning stiffness | 0–4 |
| Patient-reported swelling | 0–4 |
| Difficulty making a fist | 0–5 |
| Elevated CRP | 0–1 |
| RF positivity | 0–4 |
| ACPA positivity | 0–8 |
Maximum score without imaging: 26. MRI findings can then be added to improve precision in cases where the clinical picture is unclear. The final score assigns individuals to one of three risk categories: low, intermediate or high. Importantly, only approximately 18% of patients fell into the intermediate-risk group, meaning the majority of individuals could be assigned to a clear category — which is essential for practical use in prevention trial design.
What This Means for Patients Today
It is important to be clear: these criteria are not currently intended for routine clinical decision-making in individual patients. They have been developed primarily to standardise future prevention trials, create homogeneous research populations, facilitate regulatory pathways for preventive strategies, and deepen understanding of how RA progresses from the at-risk phase to established disease.
However, for patients who are already aware they carry RA risk factors — a family history of RA, incidental detection of positive ACPA or RF, or unexplained joint symptoms — these criteria provide a valuable framework for discussing risk with a specialist rheumatologist. The relationship between inflammatory arthritis and broader musculoskeletal health, including bone density, is also a dimension we assess as part of a comprehensive review.
What This Means for Rheumatologists
Several practical lessons emerge from this work for clinicians managing patients with arthralgia and RA risk factors.
Clinical assessment still matters
Simple, accessible symptoms — morning stiffness and difficulty making a fist — remain among the most informative predictors of future RA. Careful clinical history-taking is not superseded by technology.
Serology remains central
RF and particularly ACPA continue to be among the strongest individual predictors of disease progression. High-titre ACPA positivity in the context of arthralgia warrants close monitoring and specialist involvement.
MRI has a role in selected patients
Where clinical and serological assessment leaves genuine uncertainty, MRI — specifically looking for tenosynovitis at the wrist, MCP and MTP joints — can substantially improve risk stratification. It is not required in every case, but should be considered where the decision to enter a patient into a prevention programme depends on more precise risk estimation. For patients interested in understanding dietary and lifestyle factors alongside their serological risk, we address these in parallel.
Prevention is becoming realistic
The field is moving beyond early diagnosis towards genuine disease prevention. The challenge now is identifying those individuals most likely to benefit from preventive intervention while avoiding overtreatment in lower-risk groups — a challenge that these new criteria are directly designed to meet.
This is one of the most clinically significant papers in rheumatology in recent years. The concept of intervening before RA becomes established is not new — we have discussed it in the research setting for over a decade — but having a validated, internationally agreed risk score changes the conversation entirely. We can now point to something concrete. When a patient comes to us with arthralgia, positive ACPA and morning stiffness, we are no longer relying on clinical intuition alone to guide the urgency of that review. What is particularly interesting from a clinical standpoint is the MRI data — the finding that tenosynovitis, rather than synovitis, may be the earliest imaging signal of impending RA. We already see this pattern in practice. Equally, at the London Osteoporosis Clinic we always think about bone health alongside joint health. Patients in the pre-RA phase, especially those already taking glucocorticoids for symptom management, need bone density monitoring from the outset — this is a step that is too often delayed. The 2025 EULAR treatment recommendations and this new risk stratification work together represent a complete picture of where RA management is heading.
Looking Ahead: The Prevention Decade
This work represents a genuine milestone in the evolution of RA care. Just as cardiovascular medicine moved from treating acute events to preventing them through risk factor modification, rheumatology is beginning a comparable transition — from managing established arthritis to identifying and treating disease before it becomes clinically apparent.
The next decade may see the concept of “preventing rheumatoid arthritis” move from research aspiration to validated clinical practice. These new EULAR/ACR criteria provide the rigorous, internationally validated foundation upon which future prevention programmes, clinical trials and personalised risk management strategies can now be built [3].
Frequently Asked Questions
What is the pre-RA or “at-risk” phase of rheumatoid arthritis?
The pre-RA phase refers to a period — which can span months or even years — during which biological changes associated with rheumatoid arthritis are already occurring, but clinical arthritis has not yet developed. During this phase, autoantibodies such as ACPA and rheumatoid factor may already be present in the blood, and subtle immune changes are underway. Research has shown this window represents an opportunity for early intervention that may modify or delay the onset of established RA.
Should I ask for ACPA testing if I have joint pain but no swelling?
If you have persistent joint pain — particularly with morning stiffness, difficulty making a fist, or a family history of rheumatoid arthritis — it is worth discussing with your GP whether serological testing is appropriate. ACPA and rheumatoid factor testing is widely available and, if positive, would warrant referral to a rheumatologist for further assessment. A positive result does not mean you will develop RA, but it is an important risk factor that warrants specialist monitoring.
Can rheumatoid arthritis actually be prevented?
Prevention of RA is not yet standard clinical practice, but it is now an active and credible area of research. Clinical trials such as APIPPRA and TREAT EARLIER have shown that treatment during the at-risk phase can modify disease progression. The new EULAR/ACR risk stratification criteria are specifically designed to support future prevention trials by ensuring that the right patients are enrolled. In the next decade, it is plausible that validated prevention strategies — targeted at high-risk individuals — will enter clinical practice.
Reference: van der Helm-van Mil AHM et al. EULAR/ACR risk stratification criteria for development of rheumatoid arthritis in the risk stage of arthralgia. Annals of the Rheumatic Diseases. Published online May 2025.
Medically reviewed by Dr. Taher Mahmud, Consultant Rheumatologist and Co-Founder, London Osteoporosis Clinic. Dr. Mahmud has over 25 years of clinical experience in bone health and osteoporosis management.
This article is for informational purposes only and does not constitute medical advice. Please consult a qualified healthcare professional regarding any health concerns or before making changes to your treatment plan.
