Pos1365 Which Biomarkers Indicate Imminent Progression to Inflammatory Arthritis in High Risk CCP Positive Persons?

Background: A recently published risk stratification model proposed a simple score using 4 biomarkers to identify those at high risk of developing inflammatory arthritis (IA) for referral to secondary care 1. Meanwhile the pre-clinical phase of IA is a continuum where biomarkers evolve. Identifying those indicating imminent (6 months) progression would be of value. Objectives: In pre-clinical IA, 1. to describe sequential changes in biomarkers prior IA development according to risk stratification, and 2. to identify predictive value of biomarkers for imminent IA. Methods: In a single centre prospective observational cohort, 543 anti-cyclic citrullinated peptide antibody (anti CCP) positive persons at risk of IA with a new non-specific musculoskeletal symptom and no IA were recruited. The outcome was IA development. Risk score was calculated at first visit using anti CCP value, rheumatoid factor (RF) positivity, early morning stiffness duration (EMS) ≥ 30 minutes, and erythrocyte sedimentation rate (ESR) positivity (1), defining 4 groups; those at high or low risk who subsequently developed IA or not. Data were collected and grouped into 4 time periods prior IA: >2 years (>2Y), 2 to 1 year (2-1Y), 12 to 6 months (12-6M), and Descriptive analyses: independent and paired analysis were performed between and within groups. 2. Predictive analyses: multivariable predictive analysis for imminent IA development were conducted using panel data analysis on dichotomised biomarkers with a random intercept to account for within-person clustering and robust error estimation. Results: Of the 242/543 (45%) persons identified at high risk at first visit, 57% (139/242) developed IA in 12 (3-33) months (median IQR). Whilst only 12% (37/301) of the low risk did in 21 (9-55) months (median IQR). 1. Descriptive analyses: In the low-risk group, analysis within the small number of those developing IA (Dev IA) showed a significant increase in early morning stiffness duration (EMS) Predictive analyses: In the high-risk group, the best predictors for progression to IA within 6 months were RF positive (OR 6 CI 1-33), EMS ≥30min (OR 11 CI 2-62), US PD presence (OR 5 CI 1-21), and smJTC ≥1 (OR 5 CI 1-23). In the low-risk group, it is anti CCP >3xULN (OR7 CI 2-25), RF pos (OR 8 CI 2-32) that were the most predictive for imminent IA. Conclusion: In those at high risk of IA (for referral to secondary care); many biomarkers increased REFERENCES: 1 Duquenne L et al. Predicting Inflammatory Arthritis in At-Risk Persons: Development of Scores for Risk Stratification. Ann Intern Med. 2023. Acknowledgements: NIL. Disclosure of Interests: Laurence Duquenne: None declared, Didem Sahin Eroglu: None declared, Jianhua Wu: None declared, Andrea Di Matteo Janssen, Kate Harnden: None declared, Jacqueline Nam: None declared, Lucy Thornton: None declared, Rahaymin Chowdhury: None declared, Leticia Garcia-Montoya: None declared, Kulveer Mankia Abbvie, Galapagos, UCB, Serac Healthcare, Deepcure, Zura Bio, AZ, Gilead, Lilly, Serac, Paul Emery Abbvie, Astra-Zeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Janssen, MSD, Lilly, Novartis, Pfizer, Roche, Samsung, Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, Samsung