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Background It is known that MRI-detected subclinical inflammation in patients with Clinically Suspect Arthralgia (CSA) precedes the development of clinically evident Inflammatory Arthritis (IA). However, there are no longitudinal studies in CSA patients that did not progress to IA. The course of joint symptoms in these patients is unknown. Furthermore, it is unknown if subclinical inflammation resolves spontaneously in parallel with disappearance of joint symptoms. Objectives To determine the course of joint symptoms and of MRI-detected subclinical joint inflammation, and mutual time relationships, in patients that presented with CSA but did not progress to IA during 2 year follow-up. Methods Between April 2012-April 2014, 149 patients were included in the CSA cohort. These patients had no clinically evident arthritis but recent-onset ( Results After 2 year follow-up, 20 patients (33%) had complete resolution of symptoms whereas 40 patients (66%) did not. The remaining symptoms in the latter group were diagnosed as: persistent inflammatory arthralgia (n=26), osteoarthritis (n=6) and tendinomyalgia (n=8). In the total group, the mean total MRI-inflammation score decreased from 3.2 at baseline to 2.5 at 2 years (p=0.046). When the patients with persistent symptoms were studied, there were no significant changes in MRI-inflammation scores. Analysing the patients with resolution of symptoms separately, the total MRI-inflammation score decreased significantly (3.3 to 2.3; p=0.019). Also the total synovitis and tenosynovitis scores decreased significantly (1.3 to 0.82 and 0.83 to 0.30, respectively; p=0.043 and p=0.029), whereas BME scores remained unchanged (1.2 and 1.2; p=0.87). After 2 year follow-up the absolute MR-scores of these patients were compared to data from age-matched symptom-free controls; no differences were found for synovitis, suggesting normalisation. Physical functioning, measured with HAQ, remained similar in patients with persistent symptoms (0.56 to 0.51; p=0.61), whereas HAQ normalised in patients with resolution of symptoms (mean score of 0.15 at 2 years, p=0.053 compared to baseline). Conclusions Approximately one-third of the patients that presented with CSA and that did not convert to IA had resolution of symptoms, this was paralleled by normalisation of MRI-detected inflammation as well as physical functioning. This is the first study showing that subclinical inflammation in individuals at risk for developing RA can resolve spontaneously. The data suggest that subclinical inflammation was causally related to joint pain. Disclosure of Interest None declared

Background: Early treatment of inflammatory arthritis (IA) associates with improved outcomes. Therefore, the first recommendation in the 2016 update of the EULAR guidelines for management of early IA states that patients presenting with IA should be seen by a rheumatologist ≤6 weeks. Data on how to implement this recommendation are lacking. A screening clinic situated in between primary and secondary care, the Early Arthritis Recognition Clinic (EARC), has previously shown to increase early identification of rheumatoid arthritis patients. However, it is unknown if this effect is sustained when applied for several years and if this approach is of added value to identify patients within the 6-week limit set by EULAR. Objectives: To study if an EARC approach can lead to sustained early identification of patients with IA (as compared to regular referral to our Early Arthritis Clinic (EAC)) and to determine the efficacy to identify patients ≤6 weeks after symptom onset. Methods: To promote early recognition of IA, the EARC was initiated in September 2010 in the Netherlands. General practitioners (GPs) were instructed to refer to this screening clinic without a scheduled appointment if they were unsure about the presence of IA (instead of a ‘wait-and-see’ approach or performing additional tests). At the EARC, patients were seen for a 5-minute visit by an experienced rheumatologist who performed a full 66-joint examination for clinical synovitis. GPs can also refer directly to the EAC, where patients are seen Results: Of the 1,151 patients visiting the EARC, 475 (41%) were diagnosed with IA. Firstly, proportions of patients with IA at the EARC were studied per year. These remained stable over time: 45% in 2010, 39% in 2011, 45% in 2012, 42% in 2013 and 36% in 2014. Clinical characteristics of these patients were similar over time. In the same period 675 referred patients were diagnosed with IA at the EAC; these were compared to the 475 IA patients that were identified via the EARC. Demographic characteristics were similar. However, median symptom duration of the IA patients in the EARC-group versus the EAC-group at identification of IA were 10.7 vs 17.0 weeks in 2010 (p Conclusions: A screening clinic in between primary and secondary care has sustainable benefit with regards to early identification of inflammatory arthritis and allows >40% of patients to be identified within the timelines as recommended by EULAR. Disclosure of Interest: None declared

Background Early initiation of treatment of rheumatoid arthritis is strongly associated with an improved outcome, but requires the early identification of arthritis. Physical examination of joints is crucial to this end, but is difficult for general practitioners (GPs) who have little experience. Another difficulty is that GPs see many persons with musculoskeletal symptoms per year but only few patients with clinical arthritis. To promote early recognition of arthritis, the Early Arthritis Recognition Clinic (EARC) was initiated in Leiden, the Netherlands in 2010. GPs were instructed to refer to this clinic in case of doubt on the presence of arthritis (and not to wait and see, or to perform additional laboratory tests). At this clinic, patients filled out a form with questions on their symptoms and were seen by a rheumatologist in a short visit that comprised a full joint examination. As reported previously, this clinic importantly improved the early identification of arthritis and RA (1), but this approach may not be easily implemented in other centres or regions. Objectives To assess if a combination of symptoms and signs that are easy to assess can differentiate patients with and without clinical arthritis at joint examination. Methods 1,288 patients in whom GPs doubted on the presence of arthritis visited the EARC between 2010 and 2015. Reported symptoms and signs were studied with the presence of synovitis (joint examination by experienced rheumatologist) as outcome. Multivariable logistic regression was used. A model was derived in 644 patients, and validated in the second set of 644 patients. Results 41% of the patients who visited the EARC had arthritis at examination. Age (per year OR 1.02; 95% CI 1.01–1.03), male sex (OR 1.8; 95% CI 1.3–2.7), symptom duration (4–12 weeks OR 3.83; 95% CI 2.22–6.60), morning stiffness >60 min (OR 1.7; 95% CI 0.9–2.9), difficulty with making a fist (OR 1.6; 95% CI 0.97–2.5), number of tender joints (1–3 tender joints OR 9.7; 95% CI 1.1–81.8) and self-reported swollen joints (OR 3.5; 95% CI 1.8–7.0) were associated with the presence of arthritis in multivariable analysis. The AUC was 0.75 (SE 0.02) in the derivation set and 0.71 (SE 0.02) in the validation set. To facilitate application in practice, a simplified model was made. This consisted of 7 variables and the total score ranged between 0–7. The AUC was 0.73 (SE 0.02). Depending on the cut-off, the PPV of the simplified model ranged between 41 and 74% and the NPV between 100 and 62%. With a cut-off of 4, the NPV was 86%, PPV 49%, specificity 35%, and sensitivity 91%. Conclusions A set of clinical characteristics that can be easily assessed by GPs had a reasonable discriminative ability for clinical arthritis, and can be applied by GPs in case of doubt on the presence of arthritis. This model requires further validation in general practices, but may lead to a tool that could assist GPs in their decision making regarding referral or ordering additional tests for patients with suspected early arthritis. References van Nies JA, et al. Ann Rheum Dis. 2013;72(8):1295–301. Disclosure of Interest None declared

Background Autoantibody testing is helpful to predict progression to arthritis in subjects at risk. Previous longitudinal studies mainly focussed on autoantibody-positive arthralgia patients. Consequently predictive values of autoantibodies were evaluated relative to each other. This study assessed risks of having anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and/or anti-carbamylated protein antibodies (anti-CarP) for arthritis development in arthralgia patients considered at risk for RA by rheumatologists based on clinical characteristics (Clinically Suspect Arthralgia, CSA). Objectives To assess risks of having anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and/or anti-carbamylated protein antibodies (anti-CarP) for arthritis development in arthralgia patients considered at risk for RA by rheumatologists based on clinical characteristics (CSA). Methods Baseline ACPA, RF and anti-CarP antibodies of 241 patients, consecutively included in the CSA-cohort, were studied in relation to development of clinical arthritis during a median follow-up of 103 (IQR 81–114) weeks. Results ACPA, RF and anti-CarP antibodies were all univariably associated with arthritis development, hazard ratios (95% CI) were 8.5 (4.7–15.5), 5.1 (2.8–9.3) and 3.9 (1.9–7.7). Only ACPA, and not RF or anti-CarP, was independently associated (HR 5.1, 2.0–13.2). Relative to autoantibody-negative CSA-patients, ACPA-negative/RF-positive patients had HRs of 2.6 (1.04–6.6), ACPA-positive/RF-negative patients 8.0 (2.4–27.4), and ACPA-positive/RF-positive patients 10.5 (5.4–20.6, Figure). PPVs for development of clinical arthritis within two years were: 38% for ACPA-negative/RF-positive, 50% for ACPA-positive/RF-negative, and 67% for ACPA-positive/RF-positive patients. Higher ACPA-levels were not significantly associated with increased progression to clinical arthritis, in contrast to higher RF-levels. Autoantibody levels were stable during follow-up. Conclusions ACPA conferred the highest risk for arthritis development and had an additive value to RF. However, >30% of ACPA-positive/RF-positive CSA-patients did not develop arthritis during two-year follow-up. Thus CSA and information on autoantibodies is insufficient to accurately identify imminent autoantibody-positive RA. Disclosure of Interest None declared

Performance of the EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis - a longitudinal study

Background The clinical phase of Rheumatoid arthritis (RA) is preceded by a phase with subclinical inflammation. MRI can detect subclinical inflammation and, at patient level, this is predictive for the development of clinical arthritis. However, at joint level it is unknown how arthritis develops. It is unknown how frequently joints with subclinical inflammation progress to clinical arthritis, and vice versa, how often joints that developed clinical arthritis had local subclinical inflammation during the preceding phase of arthralgia. A longitudinal MRI study in patients that developed arthritis can unravel if arthritis development is restricted to some locations in which the severity of inflammation increases over time or, alternatively, if the process is more generalized with a weak association between the locations of subclinical inflammation and subsequent clinical arthritis. Objectives This longitudinal study at joint level during progression from pre-RA to RA determined the relation between the location of subclinical inflammation and clinical arthritis over time. Methods 290 small joints (4 MCPs, 1 wrist, 5 MTPs per person) of 29 patients that presented with arthralgia and developed clinical arthritis were studied with 1.5T MRI at both time-points. MRIs were evaluated for BME, synovitis and tenosynovitis by three readers (ICCs 0.98, 0.96 and 0.97) that were blind to clinical data and the order in time. Subclinical inflammations was defined as presence of BME, synovitis and/or tenosynovitis. Results The median time between presentation with arthralgia and clinical arthritis development was 17 weeks. At presentation with arthralgia 68 joints had subclinical inflammation and no significant association was found between joint tenderness and the presence of local MRI-detected subclinical inflammation (OR 0.98; 95% CI 0.48–1.9). Over time, 21% of 68 joints had resolution of subclinical inflammation, 60% had persistent subclinical inflammation and 19% developed clinical arthritis. At arthritis development 37 joints were swollen. Of these, 24 (65%) had no prior subclinical inflammation at the time of presentation with arthralgia (Figure). Conclusions This first longitudinal MRI-study on joint level in pre-RA suggested that the majority of joints that developed clinical arthritis had no (long-lasting) preceding phase with subclinical inflammation. Disclosure of Interest None declared

Background Subclinical joint inflammation in the phase of arthralgia preceding RA can comprise synovitis, bone marrow edema (BME) and/or tenosynovitis. It is unknown in what time order the different tissues in a joint become inflamed or progress with inflammation. It has been postulated that synovitis is an initial process that is succeeded by bone involvement (“outside-in hypothesis” presuming that synovitis precedes BME and erosions). Alternatively, it is suggested that inflammatory cells in the bone marrow migrate via bone pores to the synovium, promoting synovitis (“inside-out”, then BME precedes synovitis). Thirdly, these processes can occur or progress simultaneously. Serial MRI studies can reveal time-relationships. This longitudinal MRI study on patient-level determined the course of joint inflammation during progression from arthralgia to clinical arthritis. Objectives To increase the comprehension on the course of MRI-detected subclinical joint inflammation during progression from arthralgia to clinical arthritis, both in ACPA-positive and ACPA-negative arthritis patients. Methods We longitudinally followed 29 patients that all progressed from Clinically Suspect Arthralgia to clinical arthritis. 1.5T MRI on hand and foot joints was performed at presentation with arthralgia and subsequently at the development of clinical arthritis. MRIs were evaluated for BME, synovitis and tenosynovitis (summed in the total inflammation score) and erosions by three readers (ICCs 0.98, 0.96 and 0.97) that were blind to clinical data and the order in time. Analyses were repeated in arthritis patients that fulfilled the 2010 criteria for rheumatoid arthritis, and in ACPA-positive and ACPA-negative patients separately. Results At presentation with arthralgia the mean age was 43 years, 72% was female, and 28% was ACPA-positive. Median duration to clinical arthritis was 17 weeks. At the time of arthritis development 65% fulfilled the 2010-criteria. During progression from arthralgia to clinical arthritis the median total inflammation score increased from 4.5 (IQR 2.8–7.8) to 6.0 (IQR 2.0–13.5), p=0.01. The BME score increased over time (p=0.04), as did the synovitis score (p=0.002). The tenosynovitis and erosion scores increased as well, though not statistically significant (p=0.10 and p=0.07 respectively). Analyses within the patients that developed 2010-RA revealed that BME (p=0.047), synovitis (p=0.005) and tenosynovitis (p=0.004) all increased significantly, in contrast to the erosion score. At presentation with arthralgia, BME and synovitis scores were higher in ACPA-positive than in ACPA-negative patients; during progression to clinical arthritis the different types of inflammation increased similarly in ACPA-positive and ACPA-negative patients. Conclusions During progression from arthralgia to clinically evident rheumatoid arthritis, BME, synovitis as well as tenosynovitis progress simultaneously. Disclosure of Interest None declared