Journal Article

POS0664 PREDICTORS OF RHEUMATOID ARTHRITIS DEVELOPMENT IN AT-RISK INDIVIDUALS; A FIVE-YEAR FOLLOW-UP STUDY IN A LARGE PRACTICE-BASED COHORT

Van Schaardenburg, D., Tas, S. W., Van Vollenhoven, R. F., Landewé, R., Wagenaar, C., Frazzei, G., Van de Stadt, L. A.

2024

Overview

Background:Many rheumatoid arthritis (RA) patients experience an asymptomatic phase preceding clinical onset of disease, in which antibodies against citrullinated proteins (aCCP or ACPA) develop. These antibodies can be detected years before onset of arthritis, and along with rheumatoid factor (RF) are a risk factor for the development of RA. Moreover, in this preclinical phase of RA nonspecific signs and symptoms, such as join pain (arthralgia) and morning stiffness, may occur. However, not all RA-risk individuals will develop arthritis. Therefore, the identification of those individuals who would benefit the most from preventive treatment remains a key challenge. We analyzed data available from the expanded Reade cohort of seropositive arthralgia individuals. Part of this dataset was previously used to derive a prediction rule for the stratification of individuals at risk of developing RA (1); two hundred and thirty-four additional subjects have been included in the Reade cohort and the extended dataset was used in the analysis.Objectives:We aimed to identify predictors of RA development in a cohort of at risk-individuals with arthralgia and systemic autoimmunity associated with RA (ACPA and/or RF positive) followed for up to five years.Methods:Six hundred and seventeen ACPA- and/or RF-positive individuals with arthralgia were included in the study cohort between 2004 and 2019 and were followed up for up to five years, or until arthritis development. We performed univariable logistic regression on clinically and biologically relevant parameters, such as age, gender, smoking habit and alcohol consumption, RA family history, morning stiffness, joint tenderness and stiffness, visual analogue scale (VAS) pain, length and type of symptoms experienced, presence of shared epitope (SE), high levels of C reactive protein, and auto-antibody status. Moreover, we assessed the ability of previously mentioned baseline characteristics to predict RA development via Cox proportional hazard analysis. Alcohol consumption, morning stiffness, and SE positivity were excluded from survival analysis due to the number of missing data.Results:Univariate logistic regression showed that individuals with first degree relatives (FDR) with RA, who had intermittent symptoms < 12 months at inclusion, morning stiffness > 1 h, or were positive for shared epitope were more likely to develop RA. Moreover, antibody status was also associated with RA development: individuals with high ACPA titers or being double positive for both ACPA and RF had increased risk for developing RA compared to those with only RF or low ACPA titers. Consistent with this, survival analysis via Cox hazard analysis found that having FDR with RA, intermittent symptoms, VAS pain score ≥ 50 and antibody status were significantly associated with the risk of developing RA (Table 1). Out of the 24 subjects who had a FDR with RA, intermittent symptoms AND either high ACPA titers or were double positive for ACPA and RF, 20 individuals (83%) developed RA.Conclusion:We found that, in arthralgia individuals with systemic autoimmunity associated with RA, having a FDR with RA, intermittent symptoms, a VAS pain score ≥ 50, and high ACPA or testing positive for both RF and ACPA are predictors of future RA development. These results will aid in the identification of individuals at highest risk of developing RA, and who could benefit the most from preventive treatment.REFERENCES:[1] van de Stadt LA, Witte BI, Bos WH, van Schaardenburg D. A prediction rule for the development of arthritis in seropositive arthralgia patients. Ann Rheum Dis. 2013;72(12):1920-6Acknowledgements:NIL.Disclosure of Interests:Giulia Frazzei: None declared, Robert Landewé: None declared, Carlijn Wagenaar: None declared, Lotte A. van de Stadt: None declared, D. van Schaardenburg: None declared, Sander W. Tas: None declared, Ronald F. van Vollenhoven Consultancy and/or speaker: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, Pfizer, RemeGen, UCB, Support for Research or Educational programs (institutional grants): AstraZeneca, BMS, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi, UCB.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Alcohol use / Antibodies / Arthralgia / Autoantibodies / Autoimmunity / C-reactive protein / Citrulline / Epidemiology / Epitopes / Observational studies/ registry / Patients / Regression analysis / Rheumatoid arthritis / Rheumatoid factor / Risk factors / Scientific Abstracts / Survival / Survival analysis