SPECIFIC ACPA REACTIVITIES AND INFLAMMATORY BIOMARKERS ALONG WITH ULTRASOUND TENOSYNOVITIS ARE ASSOCIATED WITH ARTHRITIS ONSET IN A POPULATION AT RISK FOR RHEUMATOID ARTHRITIS

• Anti-citrullinated protein antibodies (ACPA) are characteristic markers for rheumatoid arthritis (RA), developing years before disease onset. Early clinical and biological biomarkers could provide useful information on the onset of RA in predisposed individuals.Objectives:The aim of the study was to investigate whether ACPA along with inflammatory markers and musculoskeletal ultrasound changes could predict arthritis development in individuals at risk for RA.Methods:ACPA-positive individuals with musculoskeletal complaints were referred from primary care to a rheumatology clinic, recruited in the Risk-RA research program and followed-up for up to 3 years, between April 2014 and October 2019. All individuals lacked arthritis both at clinical examination by a trained rheumatologist and ultrasound assessment of hands and feet and any other symptomatic joints (according to EULAR-OMERACT definition). Blood samples were collected at inclusion and were analyzed for 15 ACPA fine specificities (by custom made peptide array), 92 inflammation-associated protein biomarkers (by multiplex immunoassay with Olink extension technology) and HLA-SE (DR low resolution kit). Statistical analysis used univariate and multivariate models with backwards selection and cox regression.Results:268 individuals with a median age of 48 (36-58) were recruited, out of which 212 (79%) were females. 75 (28%) developed arthritis within 11 months of follow-up while the median follow-up for those not developing arthritis was 21 months (14-28). Increased ACPA levels, shorter symptom duration and RF positivity were the main differences between individuals developing arthritis and those who did not. In univariate models, the presence of HLA-SE, specific ACPA reactivities, certain inflammatory markers and ultrasound-detected tenosynovitis were associated with arthritis development. In multivariate analysis the presence of anti-cit-fillagrin (HR 2.1 (95% CI 1.2-3.7, p 0.01), IL6 levels (HR 1.4 (95% CI 1.2-1.7, p 0.0001) and tenosynovitis (HR 2.9 (95% CI 1.7-5.0, p 0.0001) remained significant predictors for arthritis onset.Conclusion:Certain ACPA reactivities together with inflammatory markers and ultrasound-detected tenosynovitis predict arthritis development in predisposed individuals for developing RA.Disclosure of Interests:None declared

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