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Background/Aims When the COVID-19 pandemic began, steps were taken to minimise risk to those vulnerable to severe outcomes. For immunosuppressed patients with rheumatoid arthritis (RA), consideration was given to reducing risk whilst mindful of compromising control of their underlying condition. At Leeds Teaching Hospitals NHS Trust, patients receiving rituximab (RTX) were considered for a reduced dose regimen. A retrospective study, using real-world data, was undertaken to assess the impact of lower doses of RTX on response to treatment. Methods The clinical records of all patients with RA who had received RTX between March 2020 and March 2021 were reviewed. Demographics and previous RTX exposure were recorded. The dose of RTX given during the specified period was noted. Response to treatment was recorded pragmatically by physicians as good, partial or none, based on patient reported VAS for disease activity and swollen and tender joint counts, given the limitations placed on face-to-face patient review due to the pandemic. The time to subsequent RTX treatment and the need for steroid treatment for flares was also studied. Results The number of patients treated with RTX was 282, of whom 89 patients received full dose (1g x 2 infusions), 192 patients received half dose (500mg x 2 infusions). The mean age was 61 years. 77% were female. 9% were RTX-naive, 80% had previously had full dose. Follow-up data were available for 185/192 of the group receiving 1g and 88/89 of the group receiving 2g. Clinical outcomes were as follows for the two groups (1g RTX vs 2g RTX): no response 10.3% vs 9.1%; partial response:34.9% vs 20% %; good response: 54.8% vs 70.9%. The mean length of response was 7.5 months in the patients receiving 1g of RTX compared to 8.6 months in the group receiving 2g of RTX. Similar number of patients required steroid for a flare after receiving Ig of RTX (23.9%) compare to those receiving 2g of RTX (25.8%). Conclusion A majority of patients receiving RTX for RA at either standard or reduced dose reported clinical response. Those receiving lower dose RTX were more likely to report a partial response whilst those receiving full dose were more likely to report a good response. Duration of response and need for steroid therapy for flare of RA between treatments did not significantly differ between groups. Further analysis of factors that may influence clinical response to lower dose RTX is ongoing, which could guide tailored therapy regimens should the need arise again. Disclosure J. McLorinan: None. M. Slade: None. C. Leong: None. J. Baker: None. L. Bailey: None. J. Nam: None. L. Bissell: None. P. Emery: None. S. Dass: None. B. Saleem: None.

ObjectivesTo assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs).MethodsThis prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4 weeks post-vaccination. Positive antibody response was defined as sera IgG binding to ≥1 antigen. Those that remained seronegative after first vaccination were retested 4 weeks after second vaccination; and if still seronegative after vaccination three. A T cell response was defined an ELISpot count of ≥7 interferon (IFN)γ-positive cells when exposed to spike antigens. Type I IFN activity was determined using the luminex multiplex assay IFN score.ResultsAfter vaccine one, in patients without prior SARS-CoV-2 exposure, 37/83 (45%) developed vaccine-specific antibody responses, 44/83 (53%) vaccine-specific T cell responses and 64/83 (77%) developed either antibody or T cell responses. Reduced seroconversion was seen with abatacept, rituximab (RTX) and those on concomitant methotrexate (MTX) compared to 100% for healthy controls (pConclusionPatients with RA on DMARDs have reduced vaccine responses, particularly on certain DMARDs, with improvement on subsequent vaccinations but with approximately 10% still seronegative after three doses.

The accelerated risk of cardiovascular disease (CVD) in Rheumatoid Arthritis (RA) requires further study of the underlying pathophysiology and determination of the at-risk RA phenotype. Our objectives were to describe the cardiac structure and function and arterial stiffness, and association with disease phenotype in patients with established) RA, in comparison to healthy controls, as measured by cardiovascular magnetic resonance imaging (CMR). 76 patients with established RA and no history of CVD/diabetes mellitus were assessed for RA and cardiovascular profile and underwent a non-contrast 3T-CMR, and compared to 26 healthy controls. A univariable analysis and multivariable linear regression model determined associations between baseline variables and CMR-measures. Ten-year cardiovascular risk scores were increased in RA compared with controls. Adjusting for age, sex and traditional cardiovascular risk factors, patients with RA had reduced left ventricular ejection fraction (mean difference − 2.86% (− 5.17, − 0.55) p = 0.016), reduced absolute values of mid systolic strain rate (p 2 (− 8.92, − 0.20), p = 0.041). CMR-measures predominantly associated with traditional cardiovascular risk factors; male sex and systolic blood pressure independently with increasing LVMI. Patients with established RA and no history of CVD have evidence of reduced LV systolic function and LVMI after adjustment for traditional cardiovascular risk factors; the latter suggesting cardiac pathology other than atherosclerosis in RA. Traditional cardiovascular risk factors, rather than RA disease phenotype, appear to be key determinants of subclinical CVD in RA potentially warranting more effective cardiovascular risk reduction programs.

ObjectivesTo explore the prognostic value of subclinical cardiovascular (CV) imaging measures and serum cardiac biomarkers in systemic sclerosis (SSc) for the development of CV outcomes of primary heart involvement (pHI).MethodsPatients with SSc with no clinical SSc-pHI and no history of heart disease underwent cardiovascular magnetic resonance (CMR) imaging, and measurement of serum high-sensitivity-troponin I (hs-TnI) and N-terminal-pro-brain natriuretic peptide (NT-proBNP). Follow-up clinical and CV outcome data were recorded. CV outcomes were defined as myocarditis, arrhythmia and/or echocardiographic functional impairment including systolic dysfunction and/or diastolic dysfunction.ResultsSeventy-four patients with a median (IQR) age of 57 (49, 63) years, 32% diffuse cutaneous SSc, 39% interstitial lung disease, 30% Scl70+ were followed up for median (IQR) 22 (15, 54) months. Ten patients developed CV outcomes, comprising one patient with myocarditis and systolic dysfunction and nine arrhythmias: three non-sustained ventricular tachycardia and six supraventricular arrhythmias. The probability of CV outcomes was considerably higher in those with NT-proBNP >125 pg/mL versus normal NT-proBNP (X2=4.47, p=0.035). Trend for poorer time-to-event was noted in those with higher extracellular volume (ECV; indicating diffuse fibrosis) and hs-TnI levels versus those with normal values (X2=2.659, p=0.103; X2=2.530, p=0.112, respectively). In a predictive model, NT-proBNP >125 pg/mL associated with CV outcomes (OR=5.335, p=0.040), with a trend observed for ECV >29% (OR=4.347, p=0.073).ConclusionThese data indicate standard serum cardiac biomarkers (notably NT-proBNP) and CMR indices of myocardial fibrosis associate with adverse CV outcomes in SSc. This forms the basis to develop a prognostic model in larger, longitudinal studies.

Objectives SSc primary heart involvement (SSc-pHI) is a significant cause of mortality. We aimed to characterize and identify predictors of subclinical SSc-pHI using cardiovascular MRI. Methods A total of 83 SSc patients with no history of cardiovascular disease or pulmonary arterial hypertension and 44 healthy controls (HCs) underwent 3 Tesla contrast-enhanced cardiovascular MRI, including T1 mapping and quantitative stress perfusion. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide were also measured. Results Cardiovascular MRI revealed a lower myocardial perfusion reserve in the SSc patients compared with HCs {median (interquartile range (IQR)] 1.9 (1.6–2.4) vs 3 (2–3.6), P < 0.001}. Late gadolinium enhancement, indicating focal fibrosis, was observed in 17/83 patients but in none of the HCs, with significantly higher extracellular volume (ECV), suggestive of diffuse fibrosis, in SSc vs HC [mean (s.d.) 31 (4) vs 25 (2), P Conclusion Subclinical SSc-pHI is characterized by myocardial microvasculopathy, diffuse and focal myocardial fibrosis but preserved myocardial contractile function. This subclinical phenotype of SSc-pHI was associated with high-sensitivity troponin I, N-terminal pro-brain natriuretic peptide, SSc disease severity and complicated peripheral vasculopathy. These data provide information regarding the underlying pathophysiological processes and provide a basis for identifying individuals at risk of SSc-pHI.

Patients with rheumatoid arthritis (RA) are at greater risk of major cardiovascular (CV) events, predominantly due to accelerated atherosclerosis, underpinned by inflammation and RA disease factors and also heart failure.1 Overall, modest event rate has necessitated the use of surrogate CV abnormalities of increased CV risk including arterial stiffness. Increased arterial stiffness is well recognised in established RA,2 with early, similar reports using comprehensive and reliable cardiac MRI (CMRI) in our treatment-naive, early onset RA cohort.3 Autopsy, histopathological and clinical studies in general population and RA cohorts with and without CV disease (CVD) suggest citrullinated proteins as a mechanism for atherosclerosis, including presence of citrullination within the atherosclerotic plaque of subjects without RA.4 5 We hypothesised that individuals with circulating anti-cyclic citrullinated peptide (CCP) but no systemic inflammation (of RA typically associated with increased CV risk) also demonstrate …

Background: Primary cardiac disease in systemic sclerosis (SSc-PCD) is associated with a poor prognosis when clinically evident. Subclinical SSc-PCD is described in up to 2/3 of SSc patients when sensitive methods are employed. The prognostic implication of these findings is not clear. Objectives: To describe the prevalence of cardiovascular magnetic resonance (CMR) abnormalities, their association with clinical phenotype and cardiac biomarkers, and whether cardiac biomarkers and CMR predict the development of cardiovascular (CV) events. Methods: Patients fulfilling the aCR/EULAR criteria for SSc, with no CV disease (CVD), diabetes and no more than 1 CV risk factor had 3Tesla CMR, including late gadolinium enhancement (LGE), myocardial perfusion, T1 mapping for T1 native and extracellular volume (ECV) quantification, and cardiac biomarkers measured. CV events were defined as episode of myocarditis, heart failure, rhythm disturbances and/or any echocardiographic abnormalities including systolic dysfunction, diastolic dysfunction > grade 1 or regional wall motion abnormalities. 47 healthy volunteers (HV) with comparable age and gender served as controls. Results: 83 SSc patients were recruited, median (IQR) age of 54 (49, 54), 84% females and 33% dcSSc, 40% had ILD, 24% a history of digital ulceration (HxDU) and 29% were Scl70+. CMR showed higher ECV% and T1 native, markers of diffuse fibrosis in SSc compared to HV [mean (SD) 30 (4) vs 25 (3), p= 0.000; 1241 (76) vs 1206 (55), p=0.003]. Lower myocardial perfusion reserve (MPR) was also noted in SSc patients [mean (SD) 2 (0.8) vs 3 (1), p=0.000]. None of the HV had LGE-fibrosis, whilst 16 (20%) of the patients had a non-ischemic LGE pattern. Left ventricular (LV) volume and function were similar between HV and SSc patients. Presence of LGE associated with hsTnI and lower forced vital capacity (rho=0.283, p=0.032; rho=-0.217, p=0.5). Multivariate analysis revealed an association of T1 native with mRSS and CRP (B=0.5, p=0.02; B=0.218, p=0.049). ECV% associated with NTproBNP and HxDU (B=0.032, p=0.034; B=0.310, p=0.005). 73/83 had ≥1 year available clinical and echocardiography follow up data with a mean (SD) duration of 24(20) months. 12/73 had a CV event judged to be SSc-PCD. LV mass associated with CV events(p=0.043) (Table 1), whilst univariate regression analysis showed that both hsTnI (OR=1.014, p=0.014) and NTproBNP (OR=1.005, p=0.026) but none of the CMR variables associated with the development of CV events. Conclusion: Asymptomatic SSc patients with no overt CVD demonstrate both focal and diffuse fibrosis, which are associated with cardiac biomarkers and markers of SSc disease activity. Whilst hsTnI and NTproBNP associated with the development of CV events, none of the measures of fibrosis did although a higher LV mass was noted in this group. The prognostic implications of subclinical CMR findings remain unclear and would benefit from longer follow-up. Disclosure of interests: Raluca-Bianca Dumitru: None declared, Lesley anne Bissell: None declared, Bara Erhayiem: None declared, Graham Fent : None declared, ananth Kidambi : None declared, Peter Swoboda: None declared, Helena Donica: None declared, agata Burska : None declared, John Biglands : None declared, John Greenwood: None declared, Francesco Del Galdo: None declared, Sven Plein : None declared, Maya Buch Grant/research support from: Pfizer LTD, UCB, Consultant for: abbVie, Eli Lilly, EMD Serono, Pfizer Ltd., Sanofi

Objectives: To validate enhanced liver fibrosis (ELF) test and its components-amino-terminal propeptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and HA-as biomarkers of fibrosis in SSc in an independent, international, multicentre cohort.Methods: Two hundred and fifty-four SSc patients from six Rheumatology Centres were included. Sera were collected and stored according to EUSTAR biobanking recommendations and analysed through automated high throughput diagnostics. Statistical analysis was performed with SPSS software.Results: Two hundred and forty-seven SSc patients (mean age 55.7 ± 13.9 years, 202 F) were analysed. ELF score, TIMP-1 and PIIINP levels were higher in males (P = 0.0197, P = 0.0107, P = 0.0108 respectively) and in dcSSc (P = 0.001, P = 0.0008, P < 0.0001 respectively). ELF score and the single markers significantly correlated with modified Rodnan skin score (r = 0.37, P < 0.0001), disease activity and severity (P < 0.0001 for all markers, except for HA P = 0.0001) and inversely with forced vital capacity, (FVC) % (TIMP-1, r = -0.21, P = 0.0012; PIIINP, r = -0.26, P = 0.0001), TLC% (ELF score, r = -0.20, P = 0.0036; TIMP-1, r = -0.32, P < 0.0001; PIIINP, r = -0.28, P < 0.0001), diffusion capacity of the lung for carbon monoxide (DLCO) % (P < 0.0001 for all markers, except for HA P = 0.0115). Multivariate analysis indicated that age (P < 0.001), modified Rodnan skin score (P < 0.001) and DLCO% (P = 0.005) were independently associated with ELF score.Conclusion: Between the first and this validation studies, the value of the ELF score as independent marker of skin and lung involvement in SSc is confirmed in 457 patients. A longitudinal study is on-going to identify an SSc specific algorithm with predictive value for skin and lung progression.

Background:Primary systemic sclerosis heart involvement (pSSc-HI) is described in the majority of SSc patients when sensitive methods such as cardiovascular magnetic resonance (CMR) are used1. The natural history of these subclinical findings are unknown.Objectives:To evaluate for interval change in subclinical pSSc-HI, the association between change in CMR abnormalities and disease phenotype and whether disease modifying antirheumatic (DMARD) and/or vasodilator treatment influence the CMR course.Methods:SSc patients, fulfilling the 2013 ACR/EULAR criteria, with no cardiovascular (CV) disease, diabetes and no more than 2 CV risk factors had two CMRs performed (V1 & V2; minimum 1 year apart). A 3T CMR with late gadolinium enhancement (LGE), T1 mapping for extracellular volume (ECV of diffuse fibrosis) quantification and stress perfusion was undertaken.Results:31 SSc patients were evaluated, with median (IQR) follow up (between the 2 CMR scans) of 33 (17, 37) months. Median (IQR) age was 52 (47,60), 32% had diffuse cutaneous SSc, 52% interstitial lung disease (ILD), 29% Scl70+.4/31 patients had a non-ischaemic LGE pattern suggesting focal fibrosis at V1, with no change in the pattern, distribution, or median (IQR) LGE scar mass between V1 and V2 [1.88 (1.01, 6.34) vs 1.70 (1.21, 4.18)]. At V2, 2 additional patients showed focal fibrosis, of which one had an episode of clinically diagnosed myocarditis. No significant change in ECV, T1 native, myocardial perfusion reserve (MPR) or left ventricle (LV) volumes and function were noted at V2 compared with V1 (p>0.01).SSc patients with either increase in pre-existing LGE scar mass (n=1) or new fibrosis were all dcSSc, with ILD, 2 Scl70+. A reduction in forced vital capacity and total lung capacity associated with a reduction in LV ejection fraction (LVEF) (rho=0.413, p=0.021; rho-0.335, p=0.07) and MPR (rho=0.543, p=0.007; rho=0.627, p=0.002).Patients receiving DMARD treatment had higher baseline LV end-diastolic volume compared to those with no DMARD treatment [mean (SD) 78 (19) vs 69 (10), p=0.167]. A decrease in LV stroke volume and an increase in T1 native at V1 vs V2 was noted for those on DMARD [mean (SD) 49 (8) vs 46 (8), p =0.023; 1208 (65) vs 1265 (56), p=0.008 respectively] (Figure 1). No significant change in CMR measures in those receiving vasodilator or angiotensin-converting-enzyme inhibitor treatment was noted (p>0.01).Figure 1.Mean (SD) of T1 native, LVSV/BSA, LVEF, and LVEDV/BSA at V1 compared to V2 in those with and without DMARD treatment. BSA, body surface area; DMARD, disease modifying antirheumatic drugs; EDV, end-diastolic volume; SV, stroke volume; LV left ventricular; EF, ejection fraction.Conclusion:This first, pilot longitudinal study of CMR-defined subclinical pSSc-HI suggests largely stable appearances with follow-up. Progression of new focal fibrosis and decline in LV function and MPR, where observed, associated with poor prognostic factors of SSc and ILD progression. Consistent with this, individuals on DMARD appeared to show interval decline. Larger longitudinal studies are warranted to confirm these findings and inform on utility of CMR monitoring of subclinical pSSc-HI in poor prognosis SSc.References:[1]Ntusi NA et al, J Cardiovasc Magn Reson. 2014Disclosure of Interests:Raluca-Bianca Dumitru: None declared, Lesley Anne Bissell: None declared, Bara Erhayiem: None declared, Graham Fent: None declared, Ananth Kidambi: None declared, Giuseppina Abignano: None declared, John Greenwood: None declared, John Biglands: None declared, Francesco Del Galdo: None declared, Sven Plein: None declared, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi

Background:The benefits of exercise for people with rheumatoid arthritis (RA) are now widely recognised [1]. However, exercise participation among people with RA remains low. A key reason for that could be the commonly held belief that exercise, may exacerbate disease activity while acutely increasing levels of joint pain. The association of acute exercise with pain has not been established in RA and especially in people with a recent diagnosis.Objectives:This study investigated the impact of acute aerobic-and resistance-type exercise on perceptions of pain in people with early RA.Methods:Following local NHS ethical approval, ten people with RA volunteered for the study (Age=46±13years; BMI=29.4±8.6kg/m2, RA diagnosis= 13±9months, mean±SD). Inclusion criteria were RA diagnosis (2010 EULAR criteria) within the last two years and not engaging in regular physical activity (i.e. no participation in structured exercise >2 times per week). They were assessed for maximal aerobic capacity and maximal strength at chest press, leg press and wide-grip lateral pulldown to determine intensities for exercise conditions. Thereafter they completed one no-exercise control trial (CON) and four exercise trials: 30 minutes of sub-maximal cycling at a workload equivalent to 65% VO2max (CYCLE); high intensity interval exercise consisting of 10x1 minutes cycling intervals at a workload equivalent to 95% VO2max (HIIE); resistance exercise consisting of three sets of 12-15 repetitions at 70%1RM (RES-70); resistance exercise consisting of three sets of repetitions to failure at 30%1RM (RES-30). All trials were randomised and separated by a washout period of 3-7 days. Participants completed a a visual analogue scale (VAS) for pain at baseline then 2-and 24-hours post exercise; they also completed a questionnaire related to exercise enjoyment 2-and 24-hours post exercise.Results:Currently four RA participants have completed the study and all participants completed the prescribed exercises in full. Perceived pain was low at 2 hours (0.7±0.4) and 24 hours post-exercise (1.2±0.8) for all exercise conditions (see table 1). Importantly, a difference in heart rate between the aerobic conditions (heart rate during HIIE was 16% higher than during CYCLE), and a difference in workload between the resistance conditions (RES-30 was 117% higher than RES-70) did not result in a difference in pain perception. One participant reported increased pain at 24 hours (7cm vs 1cm at 2 hours) post RES-30, but claimed that this was purely muscular and not joint pain. Interestingly, all participants enjoyed the exercises with comparable high results across the exercise conditions (see table 1).Table 1Pain and Enjoyment DescriptivesTrialBaseline VAS pain (cm)2-hour VAS pain (cm)24-hour VAS pain (cm)2-hour exercise enjoyment (1-119)24-hour exercise enjoyment (1-119)CON0.1±0.30.1±0.30.3±0.363.8±13.063.8±13.0CYCLE0.1±0.30.5±0.40.9±1.286.8±11.088.0±8.8HIIE0.1±0.31.3±1.91.1±1.785.0±27.888.3±19.1RES-700.1±0.30.4±0.40.5±0.491.3±13.088.3±6.6RES-300.1±0.30.4±0.52.4±3.188.5±17.185.0±13.1(mean±SD)Conclusion:This study identified minimal exercise effect on perceived pain at 2 hours-and 24 hours-post exercise among participants with early RA. This suggests that exercise did not exacerbate pain and importantly, high intensities and high loads did not cause additional pain. Nevertheless, further larger studies are required to examine the role of acute exercise on disease activity, e.g. inflammation, and the association with perceived pain in people with early RA.References:[1]Combe B, et al. 2016 update of the EULAR recommendations for the management of early arthritis. Annals of the Rheumatic Diseases 2016; 76: 948-959.Disclosure of Interests:None declared

OBJECTIVES: To screen for significant arrhythmias with an implantable loop recorder (ILR) in patients with SSc and no known cardiovascular disease, and identify associated disease phenotype, blood and cardiovascular magnetic resonance (CMR) biomarkers.METHODS: Twenty patients with SSc with no history of primary SSc heart disease, traditional cardiovascular disease, diabetes or maximum one traditional cardiovascular risk factor underwent clinical assessment, contrast-enhanced CMR and ILR insertion.RESULTS: ILR data were available for 19 patients: 63% female, mean (s.d.) age of 53 (12) years, 32% diffuse SSc. Eight patients had significant arrhythmias over 3 years: one complete heart block, two non-sustained ventricular tachycardia [all three dcSSc, two anti-topoisomerase antibodies (Scl70) positive, three interstitial lung disease and two previous digital ulceration] and five atrial arrhythmias of which four were with limited SSc. These required interventions with one permanent pacemaker implantation, four anti-arrhythmic pharmacotherapy, one anticoagulation.Patients with significant arrhythmia had higher baseline high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide [mean difference (95% CI) 117 (-11, 245) and 92 (-30, 215) ng/l, respectively], and CMR-extracellular volume [mean (s.d.) 32 (2) vs 29 (4)%]. Late gadolinium enhancement was observed in five patients, only one with significant arrhythmia.CONCLUSION: This first ILR study identified potentially life-threatening arrhythmias in asymptomatic SSc patients attributable to a primary SSc heart disease. Disease phenotype, CMR-extracellular volume (indicating diffuse fibrosis) and cardiac biomarkers may identify at-risk patients that would benefit from ILR screening. Future studies can inform a risk model and provide insights into SSc-associated arrhythmia pathogenesis.

Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular disease (CVD), with both traditional CV risk factors and inflammation contributing to this risk.This review highlights the burden of CVD in RA and associated traditional CV risk factors, including the complexity of dyslipidemia in RA and the so-called 'lipid paradox.' Furthermore, the recognized RA-disease-specific factors associated with higher risk of CVD and the role of systemic inflammation in the pathogenesis of CVD in RA will be addressed. With the advent of biologic and targeted synthetic therapies in the treatment of RA, the effect of conventional and newer generation disease modifying anti-rheumatic therapies (DMARDs) on CV risk and associated risk factors will also be discussed.Identifying the RA phenotype at greatest risk of CVD, understanding the interplay of increased traditional risk factors, common inflammatory processes and RA-specific factors, and personalized use of DMARDs according to disease phenotype and comorbidity to reduce this risk are key areas for future research.

Background Subclinical SSc-cardiomyopathy is described in up to 2/3 of the patients when sensitive methods such as cardiac MRI(CMR) are used. The prognostic implications and the natural history of these findings is unknown. Objectives To evaluate in SSc patients, free of cardiovascular (CV) risk factors and CV disease (CVD) the prevalence, clinical association and natural history of CMR abnormalities over 3 years. Methods 35 SSc patients, fulfilling the ACR/EULAR criteria, with no CVD, diabetes and ≤1 CV risk factor had 2 CMRs, 3 years apart. A 3T CMR with late gadolinium enhancement (LGE), T1 mapping for extracellular volume (ECV) quantification and stress perfusion(data available later)was undertaken. Initial CMR was compared with CMR results of 30 healthy controls(HC). Results 35 pts had an initial CMR:26(74%) female, mean(SD) age 55(, 13 15 (43%) dcSSc, 11 (31%) ACA+, 12 (34%) Scl70+,15 with(43%) interstitial lung disease(ILD) and 13 (37%) with history of digital ulcers(DU). 21 (60%) received any DMARD over the 3 year period and 10 (29%) prior treatment with cyclophosphamide. The first CMR(CMR1) of SSc pts vs HC showed higher ECV% values and comparable left ventricle(LV) volumes(table 1). LGE was present in 9/22 pts vs 1/30 HC. 22/35 pts had a second CMR (CMR2) at year 3(Y3). A further 5 pts had evidence of LGE, total of 14 (40%): 7/14 had dcSSc, 6/14 males, 2 ACA positive, 6 Scl70 positive. LGE distributed in the basal and mid segments, mainly in a linear or patchy pattern. Of those with LGE at CMR1 (5/9 pts with LGE on CMR1 had CMR2) no change in the LGE pattern at CMR2 was observed. None of the initial CMR measures associated with LGE development at Y3 (p>0.05). Whilst ECV had an overall decrease, ECV incresed in patients with ILD [mean diff.(CI) 3 (-1,6),p=0.14]and in those with higher mRSS at baseline(r=0.455,p=0.04). A significant decrease over the 3 years was observed in LV end-diastolic volume (LVEDV/BSA), LV end-systolic volume(LVESV/BSA) and left ventricular stroke volume (LVSV/BSA) (table 1). A decrease in LVEDV/BSA was noticed for those with a history of DU[mean diff.(CI) −5(−12,2), p=0.1], ILD[mean diff.(CI) −6(−12,0.5),p=0.07)]and shorter disease duration(r=-0.504, p=0.02). Conclusions This longitudinal CMR study in SSc demonstrates that CMR is sensitive to change over time. More individuals developed LGE (of focal fibrosis) despite immunosuppressive treatment, and ECV% (diffuse fibrosis) appeared to worsen in a poor prognostic group. Functional changes were also observed. These data justify larger studies to inform stratification strategy for CMR in SSc, and also provide new insights for further investigation. Disclosure of Interest None declared

Background Rheumatoid Arthritis (RA) patients have a prominent increase in cardiovascular disease (CVD) not fully explained by traditional risk factors 1 . Interferons type 1 (IFN-I) have been associated with premature CVD in SLE 2 and are implicated in several aspects of atherosclerosis and acute coronary syndromes 3 . A subpopulation of RA patients also display a peripheral blood IFN-I signature from 25% to 65% 4 , associated with clinical response to biologics 5 . The IFN-I signature association with CVD in RA remains unclear. Objectives To analyse expression of interferon type 1 response genes (ISGs) along a cardiac MRI (CMR) phenotyped CVD continuum in patients with RA. Methods PBMC samples from 94 RA patients and 21 healthy controls (HC) were obtained. RA patients were stratified based on CMR into: RA CMRneg (no CVD-RA, n=13), RA CMRpos (subclinical CVD-RA, n=54), and RA with clinical CVD (defined as history of cerebrovascular disease or ischaemic heart disease) (RA-CVD n=25). qPCR of ISGs was performed using TaqMan Gene Expression Assays on Biomark (Fluidigm) with compatible reagents. Factor analysis of Ct values from 51 genes was used to create scores by calculating median dCt for genes loaded by each factor. Results RA cohort median(IQR) age 63 (13.3)yrs, 69% female, disease duration 148.7 (215.3)mths; HC age 43 (16.5)y, 62% female. Three IFN-I factors (IFN Score 1, 2,3) were present in the dataset and were composed of 19, 21 and 7 genes respectively. The Jonckheere Tepstra test showed significant increases in expression of Score 2 across the 4 groups(p=0.002), consistent with a continuum, and multiplicity-corrected post-hoc analysis identified differences between HC and subclinical CVD (p=0.034), HC and RA-CVD (p=0.004); as well as between no CVD-RA and subclinical CVD-RA (p=0.034); and subclinical CVD-RA with RA-CVD (p=0.029). Scores 1 and 3 did not show consistent directional trends across all studied groups. In no CVD-RA expression of Score 1 and 2 positively correlated with CRP (rho=0.744, p=0.002 and rho=659, p=0.010 recspectively). Score 1 with Low-Density Lipoproteins (rho=0.527, p=0.044), Framingham 10y risk (rho=0.595, p=0.019) and Score 3 with Pulse Wave Velocity (rho=0.584, p=0.022). In subclinical CVD-RA score 3 expression negatively correlated with Left Ventricular mass (rho=−0.381, p=0.005), in RA-CVD score 3 expression positively correlated with Glucose (rho=0.724, p=0.042, Triglycerydes (rho=0.821, p=0.023) and Total Cholesterol/High-Density Lipoprotein ratio (rho=0.505, p=0.039). Conclusions An IFN-I score (Score 2) emerged as a possible factor characterising progression along a CVD continuum in RA patients, from no CVD to subclinical and clinical CVD; also distinguishing between HC and RA with subclinical and clinical CVD. IFN –I is involved in metabolic disturbancies associated with CVD development in RA. These results warrant further evaluation to confirm the findings in a larger cohort. References [1] Kaplan MJ. Curr. Opin. Rheumatol2006;18(3):289–297. [2] Somers EC, et al. PloS one2012;7(5):e37000. [3] de Winther MPJ. Arterioscler. Thromb. Vasc. Biol2016;36(2):217–218. [4] Rodriguez-Carrio J, et al. Front Immunol2018;8. [5] Thurlings RM, et al. Arthritis Rheum2010;62:3607–3614. Disclosure of Interest None declared

Background Cardiac involvement and in particular conduction abnormalities represent a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). No studies assessed the value of implantable loop recorder (ILR) for early detection of arrhythmias in asymptomatic patients with SSc; or whether cardiac magnetic resonance (CMR) features associate with arrhythmias. Objectives To assess the prevalence of conduction abnormalities over a 3 year period using an ILR (REVEAL) and evaluate relationship with disease phenotype, cardiac biomarkers and CMR in SSc patients. Methods 20 patients(pts) with ACR/EULAR criteria for SSc, with no history of cardiovascular (CV) disease and ≤1 CV risk factor had 3T CMR with late gadolinium enhancement (LGE) and T1 mapping for ECV quantification. An ILR was then inserted, for 3 years follow-up. ILR data were downloaded every 3 months. Serum cardiac biomarkers were also measured at the initial visit. Results 19 pts had available ILR data; 12 (63%) females, median (SD) age 53(,12 6 (32%) diffuse SSc(dcSSc), 6 (32%) ACA+, 4 (21%) Scl70+, 8 (42%)history of interstitial lung disease (ILD) and 7 (36%) history of digital ulcers (DU). 14/19 had any ILR abnormalities, 8/14 significant arrhythmias: 1 complete heart block; 2 non-sustained ventricular tachycardia (NSVT), and 5 atrial arrhythmias (1 atrial flutter, 1 AF, 1 SVT, 1 AF and SVT and 1 AF followed by atrial flutter and SVT). Of these 8 pts, 4 had dcSSc, 2 Scl70+, 4 ACA+, 3 with ILD and 3 DU history. All 3 patients with severe arrhythmias (NSVT/CHB) were dcSSc, 2 Scl70+, 2 males. Management comprised 1 permanent pacemaker implantation, 3 antiarrhythmic treatment, 1 anticoagulation.15 pts had CMR. The 8 pts with significant arrhythmia appeared to have higher ECV, LV mass, and LVEF%(table 1). LGE was observed in 1(NSVT), of a total of 5/15 with LGE. HsTnI was considerably higher in those with significant arrhythmias[(mean diff.(95% CI)117 (-10, 245)].NTproBNP [(mean diff.(95% CI) 92 (-30, 214)] also appeared greater in those with significant arrhythmias. There was no difference in CK levels between the two groups. Conclusions This pilot study demonstrates the ability of ILR to detect life-threatening arrhythmia in asymptomatic SSc pt. The data suggest CMR ECV(but not LGE) and cardiac biomarkers, in particular hsTnI (indicating subclinical myocardial injury) may be able to identify at risk pts that would benefit from ILR screening. Future studies can inform a risk model, and provide insight into the pathogenesis of SSc associated arrhythmias. Disclosure of Interest None declared

Table S1 Regression analysis of variables associated with mean carotid wall thickness in patients with RA. Table S2 Regression analysis of variables associated with maximum carotid wall thickness in patients with RA. Table S3 Regression analysis of variables associated with carotid luminal volume in patients with RA. Table S4 Regression analysis of variables associated with carotid wall volume index in patients with RA. (DOCX 28 kb)

OBJECTIVES: To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies.METHODS: Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values.RESULTS: Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007).CONCLUSION: When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX.TRIAL REGISTRATION: EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.

BACKGROUND: To report the predictive value of nail-fold capillaroscopy (NFC) patterns of vasculopathy for systemic sclerosis (Scleroderma; SSc) in an unselected cohort of patients with Raynaud's phenomenon (RP).METHODS: Patients referred to a tertiary SSc clinic with RP were evaluated by light/video-NFC. Clinical diagnosis, details and serology were recorded. Primary RP was defined as RP with no features of connective tissue disease (CTD)/antibody. NFC patterns were determined: normal, non-specific, 'early', 'active' or 'late' SSc patterns. Fulfilment of the VEDOSS or 2013 ACR/EULAR criteria for SSc was determined following NFC assessment.RESULTS: Three hundred forty-seven patients were referred: mean (SD) age 47 (15.2) years. On clinical review, 54 (16 %) did not have RP, 69 (20 %) had primary RP, 52 (15 %) had SSc and 172 (50 %) had secondary RP. NFC SSc pattern was detected in 80 (23 %) patients; 37/52 with SSc, 30/172 with secondary RP, 9/69 with primary RP and 4/54 with no RP. For identifying patients who met either the VEDOSS or 2013 ACR/EULAR criteria for SSc, detection of a SSc NFC pattern had a sensitivity of 71 %, specificity 95 %, positive predictive value 84 % and negative predictive value 90 %.CONCLUSIONS: The absence of SSc NFC pattern in patients with RP or suspected CTD is very valuable in the exclusion of SSc.

Objective: Cardiac disease in SSc can manifest in various ways and is associated with a poor prognosis. There is little evidence on how best to detect and manage cardiac disease in SSc. Our objective was to produce an expert consensus best practice pathway for the management of cardiac disease in SSc.Methods: The UK Systemic Sclerosis Study Group set up several working groups to develop a number of consensus best practice pathways for the management of SSc-specific complications, including cardiac disease. A multidisciplinary task force was convened. The guidelines were partly informed by a comprehensive literature review.Results: A best practice pathway for cardiac disease (with a focus on primary cardiac disease) in SSc is presented, including approaches for early detection and standard pharmacological and device therapies. Due to the benefits, shared care and a multidisciplinary approach are recommended. A future research agenda has been formulated in response to the relative lack of understanding of the natural history of primary cardiac disease that was highlighted by the initiative.Conclusion: The physician should be alert to the possibility of cardiac disease in SSc; it is best managed within a multidisciplinary team including both rheumatologists and cardiologists. This pathway provides a reference for all physicians managing patients with SSc.

Renal disease is a well-recognized cause of ill health and death in rheumatoid arthritis. Three broad categories of renal disease occur. The first—and by far the most common—arises from the nephrotoxicity of the drugs used in the treatment of arthritis, particularly with non-steroidal anti-inflammatory drugs. Disease-modifying antirheumatic drugs such as gold and D-penicillamine may lead to proteinuria and a glomerulonephritis in 10–30% of patients. Ciclosporin is associated with significant nephrotoxicity and hypertension. A second major but diminishing cause of renal disease in rheumatoid arthritis is amyloidosis. Thirdly, rheumatoid arthritis may be associated with the development of glomerulonephritis. The main types described are a mesangial proliferative glomerulonephritis with or without immunoglobulin A deposits, a membranous nephropathy, and a focal segmental necrotizing glomerulonephritis of the vasculitic type.Renal disease in mixed connective tissue disease and polymyositis is infrequent, but the former can be associated with a membranous and mesangial proliferative glomerulonephritis.Sjögren syndrome is rarely associated with clinically significant renal disease, but patients can present with proteinuria, acidosis, or hyperchloraemia. Interstitial nephritis and immune complex glomerulonephritis reflect the exocrinopathy and circulating immune complex disease pathognomonic of Sjögren syndrome. Evidence for effective treatment of the renal complications is lacking. Corticosteroids and cyclophosphamide are most commonly used, with newer biological drugs, such as rituximab, showing promise.

Cardiac disease is prevalent in SSc and associated with a poor prognosis. Differentiating primary myocardial disease (SSc-cardiomyopathy) from ischaemic heart disease is difficult and the disease phenotype most at risk is unclear. A comprehensive literature review was performed to inform the UK Systemic Sclerosis Study Group for cardiac disease tasked with producing a best practice pathway for the management of cardiac disease in SSc. This review describes the prevalence of SSc-cardiomyopathy, its associated greater mortality and various manifestations (e.g. heart failure, arrhythmias and diastolic dysfunction). The limited evidence suggests SSc-cardiomyopathy is associated with other poor prognostic indicators, including diffuse cutaneous disease, positive SSc-specific serology, black ethnicity, older age at disease onset, tendon friction rubs, abnormal nail-fold capillaroscopy and worse quality-of-life scores. Differentiating SSc-cardiomyopathy from ischaemic heart disease requires well-planned studies. Non-invasive investigative techniques are improving the understanding of its pathophysiological basis.

Background Rheumatoid arthritis (RA) is associated with increased incidence of cardiovascular disease (CVD) and heart failure (HF) compared to the general population. CMR studies in the general population demonstrate that increases in left ventricular (LV) mass and early LV structural changes are predictors of HF in asymptomatic patients. Previous studies have reported conflicting data on LV geometry in heterogeneously sampled RA populations. Objectives To investigate the influence of disease duration on LV geometry using CMR by assessing and comparing two distinct RA populations; a well-defined population of newly diagnosed, treatment-naive RA and an established disease group. Method Seventy-five patients underwent CMR at 3.0T (Philips Achieva TX). None had known CVD or diabetes. 30 were RA patients fulfilling 2010 ACR/EULAR classification criteria, with symptoms for less than 1 year, no therapy with disease modifying anti-rheumatic drugs, disease activity score (DAS28) ≥3.2 and at least one poor RA prognostic factor. They were age-matched with 30 RA patients with disease duration >5 yrs. 15 healthy controls were age-matched. Standard balanced steady state free precession cine images were acquired and LV dimensions calculated offline. Tissue-tagging for strain analysis was acquired using a spatial modulation of magnetization pulse sequence. Results Participant characteristics can be seen in Table 1. Age, sex, blood pressure and body size were not different between the 3 groups. The established RA group had excellent disease control with median (IQR) CRP 0.0 mg/L (5.3) and DAS28 2.0 (1.7). CMR measurements are in Table 2. LV systolic performance, using LVEF and Ecc, was normal and similar in all groups. LV geometry was similar between early RA patients and healthy controls (p-values for LVEDV, LV Mass and LV Mass/LVEDV being 0.19, 0.51 and 0.11 respectively). Indexed LV mass and LV mass/LVEDV were lower in the established RA group compared to the early RA group (Mean±SD, 33 g ± 8/m 2 vs. 43 ± 9 g/m 2 , p Conclusion We compare two distinct RA populations and demonstrate that ventricular systolic performance (LVEF and Ecc) in the RA population is similar to controls of similar age. Abnormal LV geometry (LV mass and LVmass/EDV) is prevalent in asymptomatic patients with established RA. LV remodelling appears to occur despite excellent disease control, with the caveat that this is cross-sectional disease activity. These insights suggest that ventricular remodelling occurs later in RA and that CMR is a sensitive tool to detect such changes. Additional longitudinal evaluation can inform on the impact of inflammation/disease activity over time.

Background Evidence suggests cardiovascular disease (CVD) risk in patients (pt, pts) with Inflammatory arthritis (IA), Rheumatoid arthritis (RA) is equivalent to that of type II diabetes mellitus 1 . The accepted guidance is lifestyle factor modifications should be addressed in IA 2 , but little is known of the impact of CVD risk reduction pt education programmes delivered to pts with IA within a Rheumatology service setting. Objectives To describe the utility of a comprehensive CVD risk reduction pt education programme in pts with newly diagnosed IA following a treat to target standard therapeutic regime. Methods 387 pts with IA (RA and Undifferentiated Inflammatory Arthritis: UIA) were assessed at baseline (BL) for CV risk factors (RFs) (see Table 1) Pts were; RA; pts (1987 or 2010 ACR criteria) (n=237) and UIA; pts not meeting ACR RA criteria (n=150). A standardized co-morbidity pt education programme, which included CVD risk reduction, was delivered throughout the first 12 months (M). The impact on modifiable CVD RFs was assessed at 12M. Results 108 RA, 34 UIA pts had complete datasets (see Table 1). Of those smoked at BL, 15% reported being ex-smokers at 12M and the number smoked had decreased in 44%. 10% who reported being ex-smokers at BL altered their status to never having smoked by 12M and their reported number previously smoked reduced by 43% at 12M. Alcohol use reduced in 39% and increased in 24% (overall decrease, p=0.033). At BL, 56% of pts reported doing no moderate exercise at all; at 12M around a third of the pts had either increased or decreased the amount of exercise (no overall change). Disease activity generally decreased (p Conclusions A significant reduction in alcohol units and improvement in smoking habits were seen. However, despite significant improvements in IA disease activity and mobility, there was no improvement in exercise from the low level reported at BL. The need to address modifiable CVD RFs in IA is widely accepted by Rheumatologists but effecting lifestyle change is challenging. Behavioural change in exercise is complex, particularly in chronic disease. Further studies are required to optimise the approach in IA. References Ann Rheum Dis 2009; 68:1395–1400 ARD 2010; 69:325–331 Disclosure of Interest None declared

Background SSc-CM carries a poor prognosis once clinically evident. No clear management algorithm to guide screening & investigation for SSc-CM exists. Objectives To describe cardiac MR (CMR) abnormalities in SSc pts free of CM/CVD & their association with disease (dis.) phenotype to identify the “at risk” pt. Methods We compared 35 pts with ACR/EULAR criteria SSc & no diabetes/clinical CVD who received SSc/cardiovascular (CV) profile & pulse wave velocity (PWV) assessment & 3T delayed enhancement-CMR reported by CMR-cardiologists to 30 healthy controls (HC). Univariate analysis variables (var.): CV traditional risk factors (TRF), waist/hip ratio (WHR), dis. duration, prev. digital ulceration (DU), known ILD, palpitations hx, dis. subtype, ACA, Scl70, MRSS, NFC, prev. use of cyclophosphamide, SHAQ, FVC, PASP & PWV. Results Mean (SD) age (yrs) SSc pts 55 (13), 74% female; HC 50 (15), 63% female. Median (IQR) yrs from 1st non-RP symptom 9.5 (2.3, 19.6); 43% dcSSc, 31% ACA+ve, 34% Scl70+ve, 43% known ILD, 37% DU, 0% pulmonary hypertension, 29% prev. use of cyclophosphamide. CMR markers of fibrosis were increased in SSc: ECV (31% SSc vs 25% HC, p Conclusions This study reports CMR detected sub-clinical SSc-CM with detailed SSc phenotype, associating with poor prognostic factors. These data indicate an at risk group for further evaluation that would justify more intensive monitoring for SSc-CM & its complications. The association of ECV with lower lipids/WHR, & LGE with lower BMI/sysBP is new & we postulate may reflect cachexia/medication use in severe disease. Disclosure of Interest None declared

Background The ELF test and its components (PIIINP, TIMP-1 and HA) have been shown to correlate with skin, lung and overall fibrosis and not with any vascular manifestation of Systemic Sclerosis (SSc) 1 . On the contrary, NT-proBNP has been suggested to be useful for stratification of SSc patients, especially to identify those at risk of pulmonary hypertension 2 . Objectives Aims of this study were: a) to validate ELF score and its single analytes on an independent cohort of scleroderma patients; b) to evaluate whether NT-proBNP could provide additional value to the development of an SSc-specific algorithm. Methods 250 sera from SSc patients from a single UK centre were analysed employing a high-throughput in vitro diagnostic of a routine NHS pathology lab to measure ELF score, its analytes and NT-proBNP levels. All patients fulfilled 2013 ACR/EULAR classification criteria for SSc. Clinical, laboratory and instrumental data were collected at time of sampling. Statistical analysis was performed using SPSS. P Results Multivariate analysis of ELF score (including the variables found statistically significant in univariate analysis) identified age, mRSS and DLCO% as independently associated with ELF score (p Conclusions Our findings validate the value of ELF score in a second independent cohort of 250 SSc sera and suggest that NT-proBNP has a complementary value correlating with other aspects of the disease such as PAH and heart severity. Longitudinal multicentres studies are warranted to determine the sensitivity to change and the predictive value of these biomarkers in SSc patients and to build up a new combined scleroderma specific algorithm including markers of fibrosis and vasculopathy. References Abignano G et al. Ann Rheum Dis 2014 Avouac J et al. Arthritis Care Res 2015 Disclosure of Interest None declared

Background SSc-cardiomyopathy associated conduction abnormalities carry a poor prognosis, but their pathogenesis is unclear. Early detection to prevent complications is essential. ILRs are well-established in cardiology practice. Objectives To determine the spectrum of cardiac conduction abnormalities (CCA) using the REVEAL® ILR & their association with CMR in patients (pts) with SSc with no known cardiac disease. Methods 20 pts with (ACR/EULAR criteria) SSc, with no diabetes &/or more than 1 cardiovascular (CV) risk factor, were assessed for SSc/CV profile & comprehensive CV assessment performed, inc. 3T delayed enhancement-CMR (reported by CMR-cardiologists) & ILR insertion. ILR data was downloaded 3 monthly +/− at pt request if indicated. One yr data is reported. CMR compared to 30 healthy controls. Results ILR data was available for 19 pts; 63% female, 84% Caucasian; mean (SD) age 53 (12)yrs, time from 1st non-RP symptom 9 (8)yrs; 32% dcSSc, 32% ACA+ve, 21% Scl70+ve, 54% palpitations hx, 42% known ILD, 11% DU hx, 0% pulmonary hypertension. Ten (52%) pts had ILR abnormalities; 4 with dcSSc, 3 ACA+ve, 3 Scl70+ve, 6 with palpitations hx, 4 known ILD, 3 DU hx. Subanalysis; 8 (42%) pts had supraventricular ectopics (SVE), 2 (11%) with ventricular ectopics (VE), 4 (21%) with arrhythmias of which 1 atrial flutter, 1 SVT, 1 VT & 1 complete heart block (CHB). Of the 4 pts with arrhythmias; 2 had dcSSc, 1 ACA+ve, 1 Scl70, 3 palpitations hx, 2 known ILD, 2 DU hx. Pt with CHB (dcSSc) had few SVE/VEs & 3 couplets on 24hr ECG 6 weeks previous. CMR data was available for 15 SSc pts (DE in 14; 1 pt claustrophobic, no IV access in 2, 1 CMR abandoned due to pacemaker insertion for CHB). Trend towards lower LVmass & distensibility (ie greater arterial stiffness) & higher extracellular volume (ECV, fibrosis marker) seen in pts with ILR abnormalities (p>0.05). Trend for higher ECV in those with SVE [unadj. mean difference (diff.) (95%CI) 1.1 (-2.5, 4.7)% p0.513], VE [0.7 (-4.9, 6.3)% p0.789] & arrhythmias [1.8 (-3.7, 7.3)% p0.486]. ECV was higher in SSc vs. controls; mean diff. 4.9 (3.2, 6.6)% p 2 0.568, adj. for age/sex; with trend for lower LV mass & distensibility. Conclusions This first ILR in SSc study demonstrates its utility in the incidental detection of CCA, including serious cardiac arrhythmias & suggests associated CMR abnormalities. These data support the need for identification of pts at risk that would benefit from ILR & provide insights into the pathogenesis of SSc-cardiomyopathy Disclosure of Interest None declared

Background An increased risk of heart failure in RA exists 1 . Aetiology is unclear with some evidence that cardiomyopathy may occur early in RA, from pathology distinct to atherosclerosis 3 . Large well characterised CMR-RA studies to investigate pathogenesis are few 2 . Objectives To evaluate sub-clinical CVD in an asymptomatic-CVD established RA cohort compared to healthy controls (HC), using reference standard CMR-measured outcomes & novel CMR-measures of carotid artery. Methods 76 ACR1987 RA patients (pts) with dis.>5yrs, no CVD/diabetes, assessed for CV traditional risk factor (TRFs)/RA profile, pulse wave velocity (PWV), non-contrast 3T CMR (heart & carotids) reported by CMR-cardiologists, compared to 26 HC. Carotid measures inc. mean (MWT) & maximum (MxWT) wall thickness, wall (WVol) & luminal (LVol) volume & WVol-index (WVol-I, WVol/(WVol+LVol)). UVA variables (var.)=TRFs, BMI, waist/hip ratio (WHR), HOMA-IR, NTproBNP, dis. duration (ddur), 3vDAS28, ACPA, HAQ-DI, joint surgery hx, biologic use & PWV. MVA var.=age/sex/known associated (ass.) var./UVA r>0.3. Results Mean (SD) age (yrs) of RA pts; 60 (9.2), 74% female; HC 52 (11.4), 54% female. Median (IQR) ddur 16.5 (10.7, 25.7)yrs, 81% ACPA+ve, DAS28CRP 2.59 (1.30, 3.33), 67% on biologic. There were no significant differences in lipids/glucose/HOMA-IR between RA/HC. Trend for higher NT-proBNP in RA seen. In MVA (inc. age/sex), increasing ddur ass. with NTproBNP (0.5% rise in NTproBNP per 1% increase in ddur, p0.034). RA pts (after adj. for age/sex/TRFs) had reduced LVmass/BSA, LVEF, native T1 values & increased strain (Mid-S9) vs HC; no difference seen for LVEDV, LVESV, SV, LVmass/EDV, torsion or arterial stiffness (PWV/distensibility). No significant differences in carotid measures between RA/HC seen. In RA pts, 10yr JBS2 CV risk score correlated with WVol (r0.377 p=0.004) & LVol (r0.441 p=0.001). TRFs ass. with cardiac & carotid measures in RA. Conclusions CMR evidence for reduced LV mass in RA, suggesting pathology other than atherosclerosis as the cause of heart failure; perhaps microvascular dysfunction. TRFs, not RA features, are important determinants of CMR measures of subclinical CVD in RA. References ArthRheum 2005;52:412–20 EULAR 2015 OP0163 A&R 2010:62v4 Disclosure of Interest None declared

Background Cardiac MRI (CMR) has merit in the assessment of cardiovascular disease (CVD) with increased left ventricular mass/end-diastolic volume (LVmass/EDV) associated (ass.) with greater CV risk.[1] CMR-RA studies are few; unclear if CMR assessments are applicable to RA. Objectives To describe and quantify CV risk and sub-clinical CVD in an asymptomatic (CVD perspective) established RA cohort, using gold standard CMR-measured outcomes and a clinically deliverable comprehensive CV assessment. Methods 78 RA patients (pts) (1980 ACR criteria) with disease >5yrs, no CVD/diabetes, assessed for traditional CV risk factors (RFs), RA profile, pulse wave velocity (PWV), and a subset of 58; non-contrast 3.0T CMR reported by CMR cardiologists. 10yr JBS CV risk scores calculated (x1.5 if required)[2,3]. Univariable analysis (UVA) variables marked* in Table 1. CMR values (exc. LVEF) adj. for body surface area (BSA); “abnormal” values adj. for age/sex[4]. Results 73% were female, mean (SD) age 60 (9.3)yrs, 91% white British (RA profile in Table 1). JBS risk: median (IQR) 13.3 (7.4, 20.8)%; 16 (22%) pts >20% (only 5/16 were on primary prevention therapy). Only age (B0.065, p=0.001) and syst. BP (B0.036, p 2 0.482). CMR abnormalities were common (Table 1). Greater LV mass/BSA was ass. with male gender, HTN, ever-smoking, waist/hip ratio (WHR); only gender (B13.519, p 2 0.643). Greater LVmass/EDV was ass. with male gender, age, HTN; only gender (B0.064, p 2 0.411). 59% had reduced LV mass/BSA, more common in females (69% vs. 38% males, p=0.038). LVmass/EDV was reduced referent to published controls [5]; lower in females (p Conclusions CMR-detected subclinical CVD abnormalities are common in asymptomatic RA pts and ass. with traditional CV RFs. Despite enhanced CV risk in RA, we demonstrate reduced LV mass/BSA and LVmass/EDV, similar to the only other comparably sized CMR-RA study.[5] This suggests usual LV geometry interpretations may not apply to RA and implies complex mechanisms, with perhaps different compensatory remodelling in RA; warranting further study. References JACC Card Img 2010; v3i6. Heart 2005:91:S5. ARD 2010; 69v2. www.cmr-guide.com. AR 62v4. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4079

Background Optical coherence tomography (OCT) has been recently shown to be a novel quantitative reliable tool to assess skin involvement in Systemic Sclerosis (SSc) (1). However the sensitivity to change over-time has not been evaluated. Objectives The present study aimed to compare skin assessment by OCT over-time in patients with SSc. Methods We performed 52 OCT scans of dorsal forearms on 26 sites of analysis from 17 SSc patients (9 with diffuse, 8 with limited subset according to Le Roy et al; F/M =15:2; mean disease duration at baseline ± SD =6±4.5 years) at 0 and 24 months. Clinical skin involvement was assessed using the modified Rodnan skin score (mRss). Minimum and Maximum Optical Density (Min and Max OD) of the mean-A scans were calculated employing Matlab software as previously described (1). Comparison of the mRss at the site of analysis and Min and Max OD at the 2 time-points was performed by two-tailed paired t-test employing GraphPrism software. Results Fourteen sites of analysis with local mRss=0 did not change over 24 months. Accordingly, both Min and Max OD showed only an average +2.98% and -0.05% change, respectively (p>0.05). By contrast, at 6 sites of analysis mRss improved by 2 points (three sites with local score “2” improved to “0”, three sites with local score of “3” improved to “1”). At these sites Min OD showed an average increase of 23.92% (p=0.0084) and Max OD of 25.13% (p=0.008). At 4 sites of analysis mRss improved by 1 point (two sites with local score “3” improved to “2”, one site with local score of “2” improved to “1”, one site with local score of “1” improved to “0”). At these sites Min OD and Max OD showed no significant improvement (Min OD of 1.93% and Max OD of 8.15%; p>0.05 for both). Furthermore, both Min and Max OD showed a trend towards a decrease (-3.54%, -5.41% respectively) at the 2 sites of analysis with worsening mRSS (one point increase). Conclusions Although a low number of observations, this preliminary study provides the first evidence suggesting that OCT of the skin is sensitive to change over time and is consistent with mRss. The lack of improvement of OCT findings at sites with a mRSS of 1 deserves further evaluation to determine whether this is associated with poor accuracy of mRSS or room for improvement in OCT analysis. Studies including a larger number of patients and sites of analysis with different grades of skin involvement and improvement/deterioration of clinical score are needed for more definitive validation. References Abignano G, Aydin SZ, Castillo-Gallego C et al. Virtual Skin biopsy by Optical Coherence Tomography: the first quantitative imaging biomarker for Scleroderma. Ann Rheum Dis 2013;72:1845-51. Disclosure of Interest G. Abignano: None declared, L.-A. Bissell: None declared, J. Britton: None declared, G. Lettieri: None declared, D. Woods Employee of: Michelson Diagnostics, M. Buch: None declared, D. McGonagle: None declared, P. Emery: None declared, F. Del Galdo: None declared DOI 10.1136/annrheumdis-2014-eular.4697

Background Nail-fold capillaroscopy (NFC) patterns of vasculopathy have been well described in systemic sclerosis (SSc) but few studies have reported their predictive value in an unselected cohort of patients with Raynaud9s Phenomenon (RP). Objectives To describe the association and predictive value of NFC patterns with a clinical diagnosis of SSc. Methods Patients (pts) referred to a tertiary Scleroderma clinic to aid in the diagnosis and management of RP were evaluated by light/video-NFC, performed by a fully trained physician. Data collected included clinical diagnosis, antibody (Ab) status, NFC findings and fulfilment of the VEDOSS or 2013 ACR/EULAR criteria for SSc. Primary RP (pRP) was defined as RP with no features of CTD/Ab. NFC patterns were determined: normal, non-specific, “early”, “active” or “late” SSc patterns as described. Results 347 pts were referred to the NFC service between Jan 2009 and Oct 2013; mean (SD) age was 47 (15.2) yrs, 83% were female, 26% smokers (Table 1). On clinical review, 54 (15%) did not have RP, 69 (20%) had primary RP, 52 had SSc (56% ACA+ve, 8% Scl70+ve; 67% lcSSc, 10% dcSSc, 11.5% undefined, 11.5% overlap; at referral, 29% met VEDOSS criteria, 60% met 2013 ACR/EULAR criteria), and 172 (39.5%) had secondary RP (sRP). NFC SSc pattern was detected in 80 (23%) pts: 43 with “early”, 31 with “active” and 6 with “late” pattern. 37 of the 52 patients with SSc had SSc pattern at NFC. Among the other patients with SSc pattern, 30 had sRP, 9 pRP and 4 no RP. Non-specific findings were detected in 8/52 patients with SSc, 62/172 patients with sRP, 33/69 patients with pRP and 21/54 patients with no RP. Of those without a clinical diagnosis of scleroderma (n=295), 41 (14%) met VEDOSS criteria following NFC and 4 (1.3%) the 2013 ACR/EULAR criteria for SSc. Of the 41 pts meeting VEDOSS, 28 (68%) were found to have a SSc NFC pattern. Considering the entire unselected cohort, the detection of SSc pattern on NFC had a sensitivity of 71%, specificity 95%, positive predictive value 84% and negative predictive value 90% for identifying pts who met the VEDOSS or 2013 ACR/EULAR criteria. Conclusions Our specialised NFC service improved the detection of SSc in an unselected cohort of pts with RP or suspected CTD. Pts meeting the new ACR/EULAR criteria are more likely to have a SSC NFC pattern than those meeting VEDOSS criteria. The absence of SSc NFC pattern in pts with RP or suspected CTD is very valuable in the exclusion of SSc. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1577

Background Patients with rheumatoid arthritis (RA) are at higher risk of cardiovascular (CV) disease. Emerging evidence suggests that this accelerated risk is present in the early stages of RA. Objectives Our objective was to describe the CV profile of those with a new diagnosis of inflammatory arthritis (IA). Methods 339 patients (pts) with IA enrolled into the Inflammatory Arthritis disease CONtinuum (IACON) registry in Leeds were assessed for known CV disease (CVD) and CV risk factors (RFs) including; hypertension, diabetes, smoking, family history of CVD, blood pressure, body mass index, waist/hip circumference and lipid profile. In a sub-group of those meeting ACR RA criteria (n=92); insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)) and NT-proBNP were measured. Pts were split into 3 groups; RA1; pts meeting 1987 ACR RA criteria (n=143, 42%), RA2; pts meeting 2010 ACR RA criteria (n=55, 16%) and UIA; those not meeting either ACR criteria for RA i.e. undifferentiated IA (n=141, 42%). Descriptive statistics and analysis for correlation, chi-squared and ANOVA tests were performed. Results Positivity for RF (p No differences in the prevalence of traditional CV RFs, overt CVD or metabolic syndrome (according to WHO and IDF criteria) were seen. Hypertension was prevalent across all groups (28, 27 and 25% respectively). There was a trend to significance in the prevalence of hypercholesterolaemia (26, 13 and 17% respectively, p=0.067). Similar proportions of pts within the groups were receiving anti-hypertensive, anti-platelet and lipid-lowering (LLT) therapies. Total cholesterol (TC) was lower in RA1 vs. RA2 (p=0.041) but this lost significance when results were adjusted for CRP. There was no significant difference in TC/HDL ratio. In RA1 and RA2, TC and LDL negatively correlated with CRP (p=0.003, rho=-0.402 and p=0.041, rho=-0.28 respectively), and TC/HDL ratio and HDL showed no association with CRP. Pts ACPA+ve were more likely to be smokers (27 vs. 19% ACPA–ve, p=0.016), have a past history of hypercholesterolaemia (25 vs. 15% ACPA-ve, p=0.029) and be receiving LLT (21 vs. 12% ACPA-ve, p=0.042). However, there was no significant difference in the lipid profile, even with adjustment for CRP and pts receiving LLT excluded. There was no significant difference in HOMA-IR, QUICKI and NT-proBNP between RA1 and RA2 or according to ACPA status. Conclusions Within this cohort of early IA CV RFs are prevalent, correlating with inflammation and not just a specific phenotype of RA. This supports the hypothesis that inflammation plays a key role in the known accelerated CV risk in RA, and effective treatment across the continuum is important. There may be an association between ACPA and lipid metabolism. Long-term follow-up is required to evaluate potential change in risk profile with effective disease modifying treatment. Disclosure of Interest L.-A. Bissell: None Declared, A. Burska: None Declared, S. Horton: None Declared, H. Donica: None Declared, J. Freeston: None Declared, M. Buch Consultant for: Abbot, Pfizer, Roche, Chugai, BMS, UCB, P. Emery Consultant for: Abbot, Pfizer, Roche, Chugai, BMS, UCB, MSD, J. Andrews: None Declared

Background Patients with rheumatoid arthritis (RA) have an elevated risk of cardiovascular disease (CVD), predominantly ischaemic heart disease (IHD). Systemic inflammation is thought to be a key contributor to this risk and it is hoped early therapeutic suppression of inflammation will reduce cardiovascular (CV) events in the long term. Insulin resistance, associated with metabolic syndrome, N-terminal pro-brain natriuretic peptide (NT-proBNP) and atherogenic lipid profiles have been proposed as potential surrogate measures of atherosclerosis in RA. Each has been shown to correlate with systemic inflammation, but their utility in RA above measurement of the acute phase response remains unknown. Objectives To determine whether suppression of inflammation in early RA influences surrogate measures of atherosclerosis, including the homeostasis model assessment of insulin resistance (HOMA-IR), NT-proBNP and dyslipidaemia. Methods CRP, fasting glucose and lipids, and in a sub-group, NT-proBNP and fasting insulin, were measured at baseline and week 26 in DMARD naive RA patients, with 3-12 months symptoms, recruited into the Infliximab as Induction therapy for Early rheumatoid Arthritis (IDEA) multicentre double-blind randomised controlled trial. Patients met the 1987 ACR criteria. Treatment was randomised to IFX +MTX or MTX with 250mg IV methylprednisolone as induction therapy. 120mg IM methylprednisolone was given if DAS>2.4 at 3 time points within the first 26 weeks. HOMA-IR was calculated at each time point. Descriptive statistics, Wilcoxon and paired t-test, and Spearman’s correlation were performed. Results Data from 112 patients (69% female, mean age 53 years, 55% RF and 70% anti-CCP positive) were analysed. At baseline, 9% were on a statin and 14% an anti-hypertensive agent. 4 patients had known IHD and were excluded from the subsequent analysis. The median (range) CRP was 13mg/l (0-30) with CRP normal ( 1 . In the subgroup of 79 patients with data on NT-proBNP and fasting insulin, 17% and 38% of patients had raised levels of NT-proBNP and HOMA-IR, respectively. Comparing week 26 to baseline, there was a significant fall in CRP (p Conclusions In this study, suppression of inflammation was associated with improvement in insulin resistance and increased HDL, but no significant change in NT-proBNP, TG or LDL following 26 weeks intensive RA treatment. Further analyses of biomarkers at week 78 and drug specific effects are underway. Long term follow up is being performed to determine if those patients with persistently abnormal CV biomarkers develop subclinical or overt CVD in the future despite intensive early treatment for RA. References JAMA. 2001;285(19):2486-97 Disclosure of Interest L.-A. Bissell: None Declared, S. Mackie: None Declared, L. Kozera: None Declared, J. Nam: None Declared, A. Burska: None Declared, E. Hensor: None Declared, H. Keen: None Declared, E. Villeneuve: None Declared, H. Donica: None Declared, P. Conaghan: None Declared, J. Andrews: None Declared, P. Emery: None Declared, A. Morgan Grant/Research support from: Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Limited. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Limited

Background Calcium deposits (calcinosis) in Systemic Sclerosis (SSc) are clinically heterogeneous both for site and severity of involvement. Despite often leading to complications such as digital ulcers and driving poor hand function, little attention has been paid to the pathogenesis of calcinosis and the therapeutic options remain limited. The presence of calcinosis in limited cutaneous SSc as well as in the diffuse form suggests that the condition may be associated with vasculopathy rather than fibrosis, however to date, no formal studies have addressed this hypothesis. Objectives We performed video-capillaroscopy of peri-calcinotic skin and unaffected skin in the same but contra-lateral Region of Interest (ROI), to determine whether we could detect any calcinosis – specific change in the capillaroscopic pattern. Methods Eighteen calcinotic deposits and contra-lateral ROIs were analysed with an Optilia Digital video-capillaroscopy system equipped with 200x magnification lens. For each calcinotic deposit we captured images in the 4 surrounding quadrants within 3 millimetres of the lesion. Images from each quadrant were captured, indentified and stored and in an electronic database. Analysis of the images was performed by two rheumatologists fully trained in video-capillaroscopy and blinded to the clinical details. Presence of; enlarged capillaries, Giant capillaries, Haemorrhages, Drop-out, disorganisation and capillary ramifications were assessed independently. McNemars tests were employed for statistical analysis. Results Twelve of the 18 calcinotic deposits were located at the distal phalanx, 3 at the proximal phalanx, 1 at both the middle and proximal phalanx and two at the palmer metacarpal. Drop out areas were observed in at least 1 quadrant of all 18 calcinotic deposits vs 7 contra-lateral control ROIs (p=0.05). Enlarged capillaries were observed at 17 deposits vs 11 ROIs (p =0.05), giant capillaries, disorganisation and capillary ramifications were observed at 7, 9 and 5 deposits, respectively, while none were observed in any ROIs (P < 0.05 for all). Haemorrhages were observed at 5 deposits and 2 ROIs, (P = 0.05). Conclusions This pilot study suggests that specific features of severe vasculopathy such as drop out areas, giant capillaries and disorganisation of the vascular array are observable in plain skin video-capillaroscopy and may be specifically associated with calcinotic deposits in SSc. Further studies are warranted both to unravel the role of vasculopathy in the pathogenesis of calcinosis and to determine potential benefit of therapeutic options targeting peripheral vasculopathy. Disclosure of Interest None Declared

Background Rheumatoid arthritis (RA) associated autoantibodies including anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) may be present years before clinical presentation. The pre-clinical phase of RA may also be associated with subtle CRP elevations. Objectives The study aimed to test whether CRP levels and positive ACPA autoantibodies in pre-clinical disease may be associated with small joint imaging demonstrable synovitis. Methods 21 patients identified from primary care and rheumatology clinics who were ACPA positive with musculoskeletal symptoms but without clinical synovitis, underwent 3T MRI scans of joints that were clinically uninvolved, but where early RA typically presents, namely the wrist, hand and forefeet. Pre- and post-contrast sequences images were scored blindly by 2 musculoskeletal radiologists for synovitis, bone oedema and erosions. Results 91% (19/21) patients were female, median age was 51 years and median duration of early morning stiffness (EMS) 12.5 min (range 0 to 240 min). All were ACPA+ and 57% (12/21) were RF+. Median ESR at study entry was 14.5 mm/h (range 1-40 mm/h) and median CRP using a high sensitivity CRP (hs-CRP) test was 2.7 mg/L (range All 21 cases had MRI determined synovitis. Synovitis was most frequently detected in the wrist (90.5% (19/21)). MCP synovitis was reported in 52.4% (11/21) and involvement of one or both forefeet in 66.7% (14/21). MRI determined bone oedema was evident in 52.4% (11/21) cases with 23.8% (5/21) documented in the wrists, 14.3% (3/21) in the MCPs and 33.3% (7/21) in the forefeet. MRI evident erosive change was noted in 13/21 (61.9%) of patients on MRI – 28.6% (6/21) in the wrists, 14.3% (3/21) in the MCPs and 42.9% (9/21) in the forefeet. Similar proportions of MRI changes were documented in patients who had (1) elevated CRP levels (>10mg/L) and (2) normal CRP levels ( Conclusions This MRI imaging study of small joints in ACPA positive patients who do not have clinical evidence of joint inflammation showed that patients already have MRI determined small joint synovitis, irrespective of CRP levels. In these patients, musculoskeletal symptoms may be an early indicator of the presence of clinical synovitis. The study is ongoing to determine the specificity of these findings. Disclosure of Interest None Declared

Background Rheumatoid Arthritis (RA) is associated with autoantibodies including ACPA which may be present years before clinical presentation. In the pre clinical phase, patients usually present with non specific musculoskeletal (MSK) symptoms. Objectives 1- To monitor the progression In ACPA positive patients with non specific MSK symptoms to clinical synovitis (CS). 2- To investigate if demographic, clinical, imaging, and serological measures can identify patients at high risk of developing RA at pre-clinical stage. Methods Patients were recruited from rheumatology clinics and primary care. Clinical assessment and investigations including magnetic resonance imaging (MRI) and ultrasound (US) were undertaken at baseline and 3-6 month intervals or at change of symptoms. The end point was the development of CS, defined as the presence of at least one tender and swollen joint. Healthy controls were recruited as a comparator group. Results A total of 122 patients without a diagnosis of inflammatory arthritis were studied. 22 patients were found to have CS at baseline and hence were excluded from analysis. 100 patients (73% females) with a mean age of 51 years (±11.8) had no CS at baseline and were followed up for a median duration of 38.5 weeks (range 1-234 weeks). 44 patients (44%) developed CS after a median duration of 26.5 weeks (1-170 weeks); 22 patients (22%) within 6 months and 33 (33%) within 12 months. Baseline early morning stiffness (EMS) was the only clinical parameter which demonstrated significant difference between the two groups; 59 minutes in those who progressed and 19 minutes in those who did not (P=0.001). The remaining baseline demographic, clinical, and serological parameters were not significantly different between the two groups. Baseline US of wrist and hands (controls =28, patients=98) showed a mean total power Doppler (PD) of 0.2 (SD 0.5) in the controls. In patients who did not progress, mean total PD score was 0.8 (SD 1.8) compared to 2.0 (SD 3.0) in those who progressed (p=0.003). A sub group of ACPA positive patients underwent MRI of a wrist and hand (n=33). Significant difference in flexor tenosynovitis mean score was demonstrated between groups (1.8 (SD 1.6) in patients who progressed vs. 0.7 (SD 1.1) in those with no progression, p=0.024). Conclusions A significant proportion of patients in this cohort progressed to clinical synovitis, the majority within 12 months of presentation. EMS was the only clinical parameter associated with progression. US and MRI may provide a useful tool in identifying patients who may progress to CS. Disclosure of Interest C. Rakieh: None Declared, J. Nam: None Declared, L. Hunt: None Declared, E. Villeneuve: None Declared, L.-A. Bissell: None Declared, S. Das: None Declared, P. Conaghan: None Declared, D. McGonagle: None Declared, R. Wakefield: None Declared, P. Emery Consultant for: Honoraria/Advisory Board: Abbot, Pfizer, Roche, Chugai, BMS, UCB, MSD