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 <6 months (<6M), and similarly grouped for those who did not develop IA. Biomarkers analysed were serology, inflammation markers, ultrasound (US) features, and patient reported outcomes (PROs). 1. 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) <6M prior IA and a decrease in anti CCP value in those not developing IA (Table 1). Compared to those who would not develop IA (No dev IA), in <6M prior IA, they showed higher US features, EMS, small joints tenderness count (SmJTC), and PROs (P<0.05). Anti CCP and RF value were higher throughout follow-up. In the high-risk group, analysis within Dev IA group showed significant increase in RF value, EMS, smJTC, US power Doppler (PD), fatigue and pain <6M prior IA (Table 1). Compared No dev IA, they showed similar anti CCP value but higher RF value throughout follow-up, then sequential differences with higher number of joints with US PD presence (2-1Y), ESR, US erosions and tenosynovitis (12-6M), and finally higher smJTC and EMS <6M prior IA. 2. 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 <6M prior developing clinical IA but morning stiffness duration, tenderness of the small joints, and US PD presence were the best predictors of imminent progression, therefore should be followed closely. In the low-risk group (to remain in primary care), although EMS showed significant increase, it is those with high anti CCP value and RF positive that showed the best predictive value for imminent progression. 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