Analysis of synovitis patterns in early RA supports the importance of joint-specific factors.

Background: Rheumatoid arthritis (RA) is classically considered a systemic disorder, but the role of local factors in driving synovial inflammation is increasingly being recognized. These joint-specific factors may consequently modulate disease phenotype.

Objectives: Our goal was to study the spatial distribution of swelling, tenderness and erosions in a large cohort of early RA (ERA) patients, to assess for patterns of simultaneously-involved joint clusters. We also aimed to investigate the link between arthritis localization and phenotypic features such as bone erosions and response to methotrexate therapy.

Methods: DMARD-naive patients from the ERA UCLouvain Brussels cohort were included. Forty-four joints were clinically assessed for swelling and tenderness before treatment, and 6 months later for methotrexate-treated patients. Clusters of joints were identified using Principal component analysis and Cramer's correlation coefficients. Frequency of bone erosions and joint-specific response to methotrexate were compared across different clusters.

Results: 452 ERA patients were included. Analysis of the spatial distribution of swelling and tenderness allowed for the identification of 3 joint clusters that showed significant simultaneous involvement: (i) MTP1-5 joints, (ii) hand joints (MCPs and PIPs), and (iii) larger joints. These clusters were associated with different susceptibility to bone erosions and distinct clinical features, but similar local response (joint swelling resolution) to methotrexate.

Conclusion: This is the first study investigating the spatial distribution of arthritis in a large cohort of early RA using an unbiased approach. We identify clusters of simultaneously involved joints, supporting the importance of local factors in driving synovitis in RA.