Thu0072 ultrasound Predicts Imminent Progression to Arthritis in Anti-CCP Positive at-Risk Individuals

Abstract

BackgroundUltrasound (US) Power Doppler (PD) signal is predictive for the development of inflammatory arthritis (IA) in anti-cyclic citrullinated protein antibodies positive (CCP+) individuals with musculoskeletal (MSK) symptoms but no clinical synovitis (CS) [1]. Our previous data showed a late increase in the overall US inflammation before arthritis development, suggesting that a sub-clinical phase of synovitis could be detected [2]. This abstract describes the prediction of PD abnormalities in the months following US scan.Objectives1. Presence of PD in one joint is predictive of imminent progression to IA in the next 3months.2. A rise in the number of joints with presence of PD increases the odds of progression to IA.MethodsIn a single-centre prospective observational cohort between June 2008 and December 2018, 307 CCP+ patients with a new MSK symptom but no synovitis were followed until CS occurred. Clinical and US findings were analysed. Following our previous study, we compared progression in the 3, 12 or >12 months after a US scan. 38 joints were included in the analysis (MTPs, hands, wrists, elbows, ankles and knees). Patients with palindromic rheumatism were excluded.ResultsData from 96 CCP+ at-risk patients who developed CS (progressors) are compared to 211 CCP+ patients who did not (non-progressors). Age and gender are similar, the mean follow-up of the non-progressors is higher, with significantly more smokers and high titre CCP in the progressors group (Table1).Overall, progressors have more joints with PD than non-progressors (Figure1). Patients with PD in one joint are more likely to develop CS in the following 3 months compared to those without PD (OR 7.52) and this remain significant when only the hands and wrists are included (Table2). The highest OR is shown when PD≥2 is found in at least one wrist. Similarly, there is a significant but smaller prediction of progression between 3 to 12 months after US (Table2).When a new joint develops PD, the likelihood of progression to IA within the next 3 months increases (Table2). This is especially predictive with wrists involvement (OR 3.10). Prediction of progression between 3 to 12 months before CS is significantly different between groups, with a higher OR for the wrists.ConclusionThe presence of PD in one joint and every new joint with PD are both predictive of progression to IA within the next 3months. These results should lead to a logical programme for therapy and follow -up.Abstract THU0072– Figure 1References[1] Nam J. et al., US findings predict progression to inflammatory arthritis in anti-CCP positive patients without CS. Ann Rheum Dis, 2016. 75(12).[2] Pentony P, et al., Sequential US shows a late increase in inflammatory burden in anti-ccp positive patients with non-specific MSK symptoms just before progression to IA. Ann Rheum Dis, volume 77, year 2018Table 1 demographicsProgressorsNon-progressorsp-valueN96211Age*53.4 (13)49.8 (13.2)0.494CCP titre: High/Low(%)92.7/7.350.2/48.80.000Gender F/M(%)74/2674.9/25.10.863Weeks follow-up*76.44 (93.5)...

EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

“… 77 92 In those with symptoms, the development of US synovitis appears to be a relatively late event, reflecting imminent clinical arthritis, 93 especially as more joints become involved. 94 …”

“…77 92 In those with symptoms, the development of US synovitis appears to be a relatively late event, reflecting imminent clinical arthritis, 93 especially as more joints become involved. 94 MRI studies in ACPA+ individuals with MSK symptoms and patients with CSA have identified tenosynovitis as both the most prevalent abnormality and the strongest MRI risk factor for arthritis development. 35 50 95 Tenosynovitis was the only MRI abnormality associated with arthritis progression at patient level in a study of 98 ACPA+ individuals with MSK symptoms (HR 4.02 (1.91-8.44), p=0.002).…”

What Is the Value of Ultrasound in Individuals ‘At-Risk’ of Rheumatoid Arthritis Who Do Not Have Clinical Synovitis?

“…Moreover, some might argue that US ‘sub-clinical’ inflammation might represent a late stage in the RA ‘continuum’, and when present may represent an irreversible progression to IA. Indeed, recent data suggest that the presence of PD in more the three joints, in anti-CCP ‘at-risk’ individuals, is virtually synonymous with imminent progression to RA [ 35 ]. In the context of clinical trials for disease prevention, this poses the question whether ‘at-risk’ individuals should be approached for these trials before the development of ‘sub-clinical’ synovitis.…”

A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

“…34 In a subsequent analysis of 307 subjects, the frequency of US PD at patient level (ie, number of joints affected) increased in the 12 months prior to arthritis development. 35 In a Dutch seropositive arthralgia cohort, US changes (ie, PD signal, GS synovitis, erosions) were associated with arthritis development at joint level but not patient level, although the US protocol contained fewer joints compared with the UK cohort studies. 36 In a subsequent study, GS synovitis (grade ≥2) was associated with the development of arthritis and its timing at patient level (metatarsophalangeal (MTP) joints excluded); HR 3.4.…”