Ab0203 Body Weight Is a Primary Determinant of Synovitis Severity of the Knee Across the Spectrum of Chronic Inflammatory Arthritis

Background: Obesity is a risk factor for the development of rheumatoid arthritis (RA) and serves as a negative prognostic factor for treatment response, low disease activity, and remission achievement. It affects up to 30% of RA patients, with overweight affecting up to 60%. Few studies have explored the influence of BMI on synovial histology in patients with inflammatory arthritis. Objectives: To assess the histological features of synovium associated with body mass excess among people presenting with chronic inflammatory arthritis (CIA). Methods: Thirty-four patients referred for inflammatory arthritis of the knee underwent an ultrasound (US)-guided knee biopsy between January and November 2023. The Krenn Synovitis Score (KSS) and the inflammatory infiltrate using CD68, CD138, CD3, CD20, CD34, calreticulin, and Act-ML immunohistochemical analysis were assessed. The primary outcome was body mass index (BMI). We assessed these variables of interest: inflammatory markers (ESR, CRP); medications; patient-reported outcome measures (PROMs), including disability (HAQ) and fatigue (FACIT-F) scales; tender and swollen joint counts. All patients underwent musculoskeletal ultrasound (MSUS) of the knee, and a synovitis score (SS) was calculated according to the EULAR-OMERACT guidelines. Correlations between KSS and variables of interest were assessed by the Pearson correlation coefficient. Results: We enrolled 34 CIA patients (n=13 with rheumatoid arthritis, n=12 with psoriatic arthritis, n=9 with undifferentiated arthritis). There were sixteen overweight and three obese patients, fifteen had normal BMI. Clinical characteristics, PROMs, joint counts and medications were similar between the two groups; a linear relationship existed between BMI and KSS (r=0.401, p=0.01; Figure 1A). The relationship was also consistent between BMI and each term of KSS (synovial hyperplasia, stromal cell density, inflammatory infiltrate), which was consistent across subgroups and sexes. The synovium of obese patients showed elevated expression of calreticulin, Act-ML, CD138, CD34, CD68, CD20, and CD3, and was more frequently associated with a diffuse myeloid pathotype (Figure 1B). This association was more pronounced in RA patients (p = 0.3185) than in undifferentiated arthritis (UA) and psoriatic arthritis (PsA) (Figure 1C). Additionally, a higher KSS was observed in obese patients with moderate to high disease activity (MDA/HDA) compared to the normal weight group, a pattern also noted in the low disease activity (LDA) group (Figure 1D). Furthermore, obese patients who failed biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or methotrexate (MTX) exhibited a higher KSS than those who were of normal weight (Figure 1E). Conclusion: Body mass was identified as a primary determinant of knee synovitis severity in individuals presenting with CIA, as determined by MSUS and histologically confirmed. This association was particularly pronounced in RA patients compared to PsA or UA. The correlation between BMI and synovitis appears to be partially independent of disease activity. In conclusion, BMI should be regarded as an independent factor contributing to synovial inflammation. This consideration is crucial when making treatment decisions based on MSUS and synovial pathology. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.