AN INCREASE IN ULTRASOUND JOINT INFLAMMATION OCCURS WHEN ANTI-CCP POSITIVE AT-RISK INDIVIDUALS WITH SUBCLINICAL SYNOVITIS PROGRESS TO INFLAMMATORY ARTHRITIS

K. Harnden, A. Di Matteo, D. Esperança Almeida, E. De Lorenzis, L. Duquenne, L. Garcia-Montoya, J. Nam, P. Emery, K. MankiaUniversity of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom Leeds Teaching Hospitals Trust, Rheumatology, Leeds, United Kingdom Hospital de Braga, Serviço de Reumatologia, Braga, Portugal The Rotheram NHS Foundation Trust, Rheumatology, Rotherham, United Kingdom  Background Anti-CCP+ at-risk individuals with musculoskeletal (MSK) symptoms and subclinical synovitis on ultrasound (US) are at high risk of developing inflammatory arthritis (IA). The accepted standard practice is to initiate treatment at progression rather than in the pre-rheumatoid arthritis (RA) phase when they do not have clinical synovitis [1]. Objectives We aimed to determine whether imaging characteristics change when individuals with pre-RA progress to IA in order to inform the optimal window of opportunity for therapeutic interventions. Methods Anti-CCP+ at-risk individuals with MSK symptoms but no clinical synovitis from the Leeds CCP cohort were selected for having US subclinical synovitis [Grey scale (GS) ≥1 and Power Doppler (PD) ≥1] prior to IA development and a further US scan performed at clinical synovitis onset (i.e. progression). The US protocol included the metacarpophalangeal joints (MCPJs), proximal interphalangeal joints, wrists, elbows, knees, ankles, second-fifth metatarsophalangeal joints, extensor carpi ulnaris and finger flexor tendons. US PD and GS synovitis were scored semi-quantitatively (0-3) according to EULAR/OMERACT. At patient level, total GS and PD scores were compared between scans. Change on US in the joints that became clinically swollen was also assessed. Early morning stiffness (EMS) and 44 tender joint count (TJC) were compared between scans. Wilcoxon signed-rank tests were conducted for comparisons. Results Forty-six CCP+ at-risk individuals were identified. The mean age was 57.4 (± 13.3), 91.3% had high titre CCP levels (≥ 3x upper limit of normal) and 60.9% were Rheumatoid Factor positive. The median US scan interval was 3.5 months (IQR 1.25-8.75). EMS increased between scans (median of 20 [IQR 0-60] to 75 [IQR 30-173] minutes [p = 0.048]) as did TJC (median 2 [IQR 1-7] to 6 [IQR 2-13] [p=0.001]. On US (Table 1), at patient level the overall burden of PD in the joints increased at IA progression, trending towards significance. The overall burden of GS did not increase. PD in the MCPJs and MCP and wrist joints combined increased significantly. GS at the elbows also significantly increased. There was no significant increase in tendon GS or PD. At joint level PD increased in joints that were swollen at progression and GS increased with a trend towards significance. Non-swollen joints did not change. Conclusion A marked increase in US joint inflammation occurs when CCP+ at-risk individuals with subclinical synovitis on US progress from pre-RA to clinical arthritis. This is particularly evident in MCPJs, wrist joints and joints that become clinically swollen. This marked increased in ultrasound joint inflammation at progression is accompanied by a significant increase in EMS and tender joints. Intervening when at-risk individuals have subclinical synovitis may represent a window of opportunity to prevent the rapid increase in ultrasound joint inflammation that occurs with the onset of joint swelling. Table 1. Changes on Ultrasound from first visit with subclinical synovitis to second visit at progression to RA. Visit 1: US subclinical synovitis Visit 2:Progression to IA P-value Total PD score* 3 (1.25-5) 4 (2-7.25) p=0.063 Total GS score* 23 (12-28) 21 (13-33.5) P=0.170 PD score MCPJs* 0 (0-2) 1.5 (0-3) p=0.008 GS score MCPJs* 5 (3-10) 5 (2.7.75) p=0.139 PD score Wrists* 1 (0-2) 1 (0-2) p=0.153 GS score Wrists* 3 (2-4) 3 (2.25-4) p=0.181 PD score MCPJs + Wrists* 1 (0.25-3) 2 (1.25-4.75) p=0.002 GS score MCPJs + Wrists* 10.5 (6-16.8) 12 (7.25-15.8) p=0.337 PD score Elbows* 0 (0-0) 0 (0-0) - GS score Elbows* 0 (0-0) 0 (0-1) p=0.009 GS score in Joints that became swollen at IA progression* 3 (1-5) 3 (2-6,5) p=0.061 PD score in Joints that became swollen at IA progression* 1 (0-2) 2 (0-3) p=0.036 *Median (IQR) References Rogier et al. Subclinical synovitis in arthralgia: how often does it result in clinical arthritis? Reflecting on starting points for disease-modifying anti-rheumatic drug treatment. Rheumatology (Oxford). 2021 Aug 2;60(8):3872-3878 Acknowledgements: NIL. Disclosure of Interests Kate Harnden: None declared, Andrea Di Matteo: None declared, Diogo Esperança Almeida: None declared, Enrico De Lorenzis: None declared, Laurence Duquenne: None declared, Leticia Garcia-Montoya: None declared, Jacqueline Nam: None declared, Paul Emery Consultant of: BMS, AbbVie, MSD, Pfizer, Novartis, and Roche, Grant/research support from: AbbVie, BMS, Lilly, Samsung, Kulveer Mankia Speakers bureau: Abbvie, Lilly, UCB, Grant/research support from: Gilead, Lilly. Keywords: Ultrasound, Rheumatoid arthritis, Imaging DOI: 10.1136/annrheumdis-2023-eular.761Citation: , volume 82, supplement 1, year 2023, page 488Session: Rheumatoid arthritis - prognosis, predictors and outcome (Poster View)