Background/Purpose: Despite animal models, little is known about synovial tissue (ST) composition of overweight/obese Rheumatoid Arthritis patients. The aim of the study was to investigate the impact of high Body Mass Index (BMI) on ST inflammation of RA patients from disease onset to stable remission achievement.

Methods: One-hundred twenty five RA patients [(57 DMARDs naïve, 43 Methotrexate inadequate responder (MTX-IR) and 25 in stable clinical (DAS<1.6) and ultrasound remission under MTX+TNF-i respectively] were enrolled and underwent ST biopsy. At study entry RA patients were divided based on BMI (kg/m²) in normal weight (BMI<25), overweight (BMI>25) and obese (BMI>30) respectively. Immunohistochemistry for CD68⁺, CD21⁺, CD20⁺ and CD3⁺ cells was performed. Each naive RA patient was treated according to the treat to target (T2T) strategy and followed for 12 months.

Results: Among the whole RA cohort, naïve RA were younger (53.5 ± 15.4 years) than MTX-IR RA (59.5 ± 13.8 years) and RA patients in stable remission (57.2 ± 15.0; p=0.02 using ANOVA test), whereas there were no significant differences in terms of other demographic, immunological and clinical characteristics comparing naive to treatment and MTX-IR RA patients. The overweight/obesity rate was comparable between the 3 subgroups [34(59.6%) naïve RA vs 25(58.2%) MTX-IR RA vs 14(56.0%) RA in stable remission were overweight/obese, p>0.05]. However, naive RA patients with BMI>30 kg/m² showed more likely follicular synovitis (78.6%) than normal weight naïve RA (39.1%; p=0.02). Particularly, naive RA with BMI>35kg/m² showed higher histological scores for CD68⁺ (p=0.03 and p=0.01 for lining and sublining), sublining CD20⁺ (p=0.005), CD21⁺ (p<0.001 and p=0.003 for lining and sublining) and sublining CD3⁺ cells (p=0.003) than normal weight naïve RA. Moreover, BMI directly correlated with synovial aggregate grade (R=0.311; p=0.02) and histological scores of CD21⁺ (R=0.344; p=0.01), CD20⁺ (R=0.295; p=0.03) and CD3⁺ cells (R=0.256; p=0.05) in naive RA. Conversely, MTX-IR RA patients showed similar synovial inflammation degree based on different BMI categories. Regardless of the synovial inflammatory pattern (follicular vs diffuse), naive overweight/obese RA patients showed a worse clinical response to T2T strategy compared to normal weight naive RA at 6 and 12 months follow-up respectively (p<0.05 for both). Finally, despite RA in stable remission showed lower disease activity index (DAS) and inflammatory markers (ESR and CRP) than naïve RA (p<0.001 for each comparison), overweight/obese RA in stable remission showed higher degree of residual synovial inflammation in terms of sublining CD68⁺ cells (p=0.001), lining CD20⁺ cells (p=0.04), and lining and sublining CD3⁺ cells (p=0.04 and p=0.05 respectively) compared to normal weight RA patients in stable remission.

Conclusion: Overweight and obesity are associated with higher degree of histologically proven synovitis in RA patients from the time of disease onset to the achievement of stable remission influencing the response rate to T2T regimen. These findings suggest that BMI control should be a key target during the whole disease course in RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/overweightobesity-affect-histological-features-of-synovial-membrane-of-rheumatoid-arthritis-patients-from-disease-onset-to-stable-remission-achievement/