Advances in the field of emerging rheumatoid arthritis (RA) paved the way for studies aiming to prevent RA development. Individuals at risk for RA can be identified with a combination of symptoms while clinical arthritis is still absent (Clinically Suspect Arthralgia, CSA). Recent proof-of-concept prevention trials showed delay or disease modification, but no prevention of RA development. Apparently, key mechanisms for chronicity are not specifically affected by anti-CD20 and methotrexate. With the ultimate aim to achieve targeted prevention, I propose to start research into subclinical inflamed tissue to gain insight on key mechanisms underlying progression from CSA to RA.
Project LeadDr. Hanna van Steenbergen
The aim is to decipher the immune cell composition and their spatiotemporal organization in subclinical inflamed synovium and/or tenosynovium that is specific for progression from CSA (with subclinical inflammation) to RA (with clinical and chronic inflammation). This knowledge may contribute to ultimately reach targeted prevention in the pre-arthritis phase.
Milestone at 1 year (after first stage of fellowship): the ultrasound-guided biopsy technique is learnt and I am experienced to perform it in in my home center. If necessary, rehearsal periods will be possible at the host center to strengthen my skills along all the study phases. Embedding in my home center is ensured by an interventional radiologist who was involved in the pre-work In addition, the host center has full equipment to perform DSP analyses and I have learned this technique.
Milestones at 3 year (after second stage of fellowship): 40 patients with CSA and subclinical inflammation underwent biopsy (and additionally 10 RA patients and 10 post mortem persons without rheumatic disease). The CSA patients will be longitudinally followed for at least 2 years until arthritis/RA development. IMC and DSP baseline findings have been compared. Results will be presented at scientific meetings, in scientific publications and meetings for patient partners and laymen.
Forty patients with CSA and subclinical MRI-detected inflammation of the synovium and/or tenosynovium of the hand/wrist consecutively included in the CSA cohort of the home center will be selected. The home center has longstanding expertise in basic, translational and clinical research on the early phases of RA and since 2012 an ongoing observational cohort of CSA patients (currently >800 patients included).