Early recognition and prevention of RA

Aim

Despite advancing treatment strategies, rheumatoid arthritis remains a chronic disease that has lifelong symptoms and impairments and requires lifelong management. As a result, prevention of rheumatoid arthritis has become a definitive target. Precision prevention requires to address the right process with the right drug in the right patient at the right time.

To achieve this goal, our group performs both observational and interventional studies. Traditionally, we worked on the stage of classified arthritis, but over the past decade we have shifted to the pre-disease stage of clinically suspected arthralgia.

In short, the aim of our group is to  1) unravel the pathogenesis of RA development and disease progression, 2) develop adequate methodology for identification and risk stratification for patients with suspected RA, and 3) to prevent RA or diminish the disease burden.

To this aim we apply an integrated approach to basic research and patient care with cross-disciplinary collaboration (biologists, immunologists, radiologists, engineers) in the Medical Delta (in collaboration with Erasmus MC and TU Delft).

Cohorts and future

The integration between clinic and basic/translational research is exemplified by our Early Arthritis Clinic (EAC). Starting in 1993, over 4500 patients are followed longitudinally for diagnosis, disease activity, function, and destruction as measured by imaging techniques, serologic, genetic and cellular parameters. Some patients have been followed for >25 years.

The aim is to increase the knowledge and understanding of risk factors for development of the disease, to develop diagnostic and prognostic algorithms and to improve the effectiveness of therapeutic strategies.

Our Clinically Suspect Arthralgia (CSA) cohort includes patients in the symptomatic risk stage of arthralgia that precedes clinically apparent arthritis and RA. The first patient was included in 2012. This cohort aims to increase the comprehension of the development of RA, using imaging of joints (detection of subclinical joint inflammation and differentiating this from normal variants, and developing short MRI sequences to facilitate implementation of MRI in clinical practice), functional tests of e.g. hand function, and serologically expressed inflammatory markers (transcriptomics, proteomics). Thorough studies on parameters during the transition from CSA to RA or to spontaneous resolution can reveal the mechanisms that are decisive for disease chronicity. In addition to the Leiden CSA cohort, a completely similar multicenter CSA cohort started in the Rotterdam area in 2017; this is led within a Medical Delta partnership, facilitated by the position of prof A van der Helm in the LUMC and Erasmus MC.

An intervention trial in patients with CSA and subclinical joint inflammation is the TREAT EARLIER trial. TREAT EARLIER is short for: Treat Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis. This is a region-wide proof-of-concept trial in the Medical Delta that studies whether progression to persistent clinical arthritis/RA or the disease burden can be reduced by a temporary treatment with methotrexate. This trial started in 2015. The five year follow-up is completed in 2025 and the long-term preventive effects are being assessed.

Allowing early access to rheumatologic care is crucial. Since 2010 our department has a “quick-walk in“ screening (outpatient) clinic, named the Early Arthritis Recognition Clinic (EARC), where patients can be referred to by their General Practitioner and which is easily accessible (1.5 lines setting, in between primary and secondary care). This benefits both clinical practice and research. Eligible patients visiting the EARC are asked if they are willing to participate in our cohorts and studies.

The studies in our cohorts are performed by clinicians, immunologists, biologists, epidemiologists and are supported by research nurses and  data managers.

In sum the research is aimed at early access to medical care, timely diagnosis and very early personalized intervention, aiming at precision prevention.