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We sought to determine whether the increased risk of atrial fibrillation and stroke in rheumatoid arthritis (RA) can be accounted for by an increased prevalence of electrocardiographic markers of atrial myopathy.We retrospectively evaluated clinical and electrocardiographic data of 218 RA patients prospectively enrolled in the Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis study (EDRA study ClinicalTrials.gov: NCT02341066) and 109 controls matched by age and gender. The prevalence of interatrial blocks (IAB, partial - pIAB or advanced - aIAB), abnormal P-wave terminal force in lead V1 (aPtfV1) and atrial myopathy (electrocardiographically defined as the presence of 1) aIAB, or 2) pIAB plus abnormal aPtfV1) was assessed in each group. RA patients were followed-up for 5 years for incident atrial fibrillation and cardiovascular events.Barring the prevalence of hyperlipidaemia and obesity, the demographic characteristics and cardiovascular risk profile of RA patients and controls were comparable. All subjects enrolled in the study were free from previous cardiovascular disease and atrial fibrillation. Compared to controls, RA patients had longer P-wave duration (118±12 vs. 112±10 ms, p0.001) and higher prevalence of pIAB (43% vs. 21%, p0.001) and abnormal PtfV1 (27% vs. 10%, p0.001). Accordingly, atrial myopathy was significantly more prevalent (15% vs 4%, p=0.003) in RA patients. In multiple regression, male gender (OR [95% CI] = 3.09 [1.48-6.47], p=0.003) and RA (OR [95% CI] = 4.83 [1.58-14.73], p=0.006) were independently associated with atrial myopathy. Atrial myopathy was not significantly associated with incident atrial fibrillation or cardiovascular events in RA patients after 5 years of follow-up.Electrocardiographic markers of atrial myopathy are independently associated with RA. Further studies with larger sample size and longer follow-up are needed to determine whether the increased prevalence of atrial myopathy contributes to the increased risk of atrial fibrillation and stroke in this group.

OBJECTIVE To compare the effect of achievement and maintenance of Lupus Low Disease Activity State (LLDAS) and clinical remission (CR) in preventing early damage accrual in patients with systemic lupus erythematosus (SLE). METHODS In a monocentric cohort of 116 newly diagnosed SLE patients, LLDAS and CR achievement at 6 months (T1) after treatment initiation and their maintenance over the next 12 months were assessed. Early damage was recorded after 18 months of follow-up (T2) using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Univariate and multivariate analyses were performed to evaluate the association of LLDAS and CR with early damage. RESULTS LLDAS was significantly more attained than CR both at T1 (42.2% versus 21.6% of patients; P < 0.001) and T2 (46.6% versus 31.9%; P = 0.022). The overlap rate between persistent LLDAS and persistent CR was 41.7% (n = 15). On multivariate analysis, achievement of CR (odds ratio [OR] 0.07 [95% confidence interval (95% CI) 0.01-0.59], P = 0.015) and LLDAS (OR 0.25 [95% CI 0.06-0.99], P = 0.049) at T1 were independently associated with lower accrual of early damage. Patients who achieved LLDAS (including CR) at T1 and steadily persisted in this condition until T2 developed significantly less damage compared to those who failed to maintain it during the T1-T2 interval (P = 0.003), those who achieved it later than T1 (P < 0.001), or those who had never been in this condition (P < 0.001). CONCLUSION Although CR is recommended as the primary treatment target in SLE, LLDAS represents a valid alternative in the early stage of SLE management. LLDAS and CR maintenance should be targeted to prevent damage.

ObjectiveA subanalysis of the multicentre Early Lupus inception cohort was performed to investigate the real-world Glucocorticoids (GCs) Use in newly diagnosed systemic lupus erythematosus (SLE) Patients (GULP).MethodsPatients starting prednisone (PDN) ≥5 mg/day and concomitant hydroxychloroquine or immunosuppressant within 12 months of SLE classification were enrolled. Core set variables were recorded at baseline and every 6 months, including changes in PDN dose, European Consensus Lupus Activity Measurement (ECLAM) and Systemic Lupus International Collaborating Clinics damage index. Regression models analysed predictors of tapering PDNResultsThe GULP study included 127 patients with SLE; 73 (57.5%) tapered and maintained PDN ConclusionTapering PDN

Several cardiovascular (CV) risk algorithms are available to predict CV events in the general population. However, their performance in patients with rheumatoid arthritis (RA) might differ from the general population. This cross-sectional multicentre study aimed to estimate the 10-year CV risk using two different algorithms in a large RA cohort and in patients with osteoarthritis (OA).In a consecutive series of RA patients and matched OA controls without prior CV events, clinical and serologic data and traditional CV risk factors were recorded. The 10-year CV risk was assessed with the Systematic COronary Risk Evaluation (SCORE) and the "Progetto Cuore" algorithms.1,467 RA patients and 342 OA subjects were included. RA patients were more frequently diabetic (9.9% vs 6.4%; p=0.04) and smokers (20.4% vs 12.5%; p=0.002) but had lower prevalence of obesity (15% vs 21%; p=0.003). Dyslipidaemia was more prevalent in OA (32.5% vs 21.7%; p0.0001). The 10-year estimated CV risk was 1.6% (95%CI 1.3-1.9) in RA and 1.4% (95%CI 1.3-1.6) in OA (p=0.002) according to SCORE and 6.5% (95%CI 6.1-6.9) in RA and 4.4% (95%CI 3.9-5.1) in OA (p0.001) according to "Progetto Cuore". Regardless of the score used, RA patients had a 3- to-4-fold increased 10-year risk of CV events compared to OA subjects.RA patients have a significantly higher 10-year risk of CV events than OA subjects. In addition to effective disease control and joint damage prevention, specific protective measures targeting modifiable traditional CV risk factors should be implemented in RA.

ObjectiveThe Physician Global Assessment (PGA) is a visual analogue score that reflects the clinician’s judgement of overall SLE disease activity. The aim of this systematic literature review is to describe and analyse the psychometric properties of the PGA.MethodsThis systematic literature review was conducted by two independent reviewers in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All articles published through 1 July 2019 in PubMed were screened, with no limitation on year of publication, language or patients’ age. Psychometric properties data were analysed according to the OMERACT Filter methodology version 2.1.ResultsThe literature search identified 91 studies. Face validity was reported in all the articles retrieved in which the PGA was used alone or as part of composite indices (Systemic Responder Index, Safety of Estrogen in Lupus Erythematosus National Assessment Flare Index, Lupus Low Disease Activity State, Definitions of Remission in Systemic Lupus Erythematosus criteria). Content validity was reported in 89 studies. Construct validity was demonstrated by a good correlation (r ≥ 0.50) between the PGA with the SLEDAI (12 studies), SLAM (4 studies), LAI, BILAG and ECLAM (2 studies each). Criterion validity was assessed exploring the PGA correlation with quality of life measurements, biomarker levels and treatment changes in 28 studies, while no study has evaluated correlation with damage. A good responsiveness for PGA was shown in eight studies. A high variability in scales was found, causing a wide range of reliability (intraclass correlation coefficient 0.67–0.98).ConclusionPGA is a valid, responsive and feasible instrument, though its reliability was impacted by the scale adopted, suggesting the major need for standardization of its scoring.

Purpose To explore the potential role of circulating endothelial cells (CECs) and their progenitors (EPCs) as biomarkers of disease activity and damage accrual in patients with Behcet's syndrome (BS), by using a standardised and reliable flow cytometry protocol. Patients and methods CECs and EPCs were assessed in 32 BS patients and 11 gender/age/smoking habits matched healthy controls (HC). They were identified by flow cytometry as alive/nucleated/CD45-negative/CD34-bright/CD146-positive and alive/nucleated/CD45-negative/CD34-bright/CD309-positive events, respectively. In BS patients, demographic and clinical features, including disease activity (assessed by Behcet's disease current disease activity form, BDCAF) and irreversible damage accrual (by the vasculitis damage index, VDI) were recorded. Uni- and multivariate analysis were performed to compare the CECs and EPCs concentrations in BS vs HC and to identify potential associations with demographic or clinical features. Results The CECs concentration was significantly higher in the BS patients than HCs [median (IQR) 15.0 (7.5-23.0) vs 6.0 (2.0-13.0) CECs/mL, p=0.024]. In BS patients, no significant associations were found between CECs and demographic features, present and past clinical manifestations, BDCAF score and ongoing treatment. A significant association was observed between CECs and organ damage, as assessed by the VDI (rho 0.356, p=0.045). Higher levels of CECs were especially associated with vascular damage [median (IQR) 23.0 (14.0-47.0) vs 13.0 (6.0-19.0) CECs/mL, p=0.011], including arterial aneurysm and stenosis, complicated venous thrombosis, cerebrovascular accident. The concentration of EPCs did not significantly differ between the BS and HC [median 26.5 (13.0-46.0) vs 19.0 (4.0-42.0) EPCs/mL, p=0.316] and no significant associations were observed between their levels and any clinical characteristic. Conclusion Our study suggests that the CECs concentration is significantly higher in BS than healthy subjects, and it mainly correlates with vascular damage. A longitudinal extension of the present study on a wider cohort would be useful to validate the potential role of CECs as a marker or, hopefully, predictor of vascular damage in BS.

Specific and high-quality evidence on the efficacy of the current targeted therapies for axial disease in psoriatic arthritis (axPsA) is still scarce. Indeed, almost all the cohorts investigated in clinical trials on PsA consisted of patients with peripheral arthritis, where a small number of them also had axial involvement. Only one randomized controlled trial was so far specifically designed to assess the efficacy of a biological disease-modifying antirheumatic drug (DMARD) in axPsA. For other biological and synthetic targeted DMARDs, the most specific evidence for treatment in axPsA is extrapolated frompost-hocanalyses based on PsA patients with concomitant peripheral and axial manifestations. Furthermore, the current trials andpost-hocanalysis on axPsA are affected by major limitations, including the lack of a widely accepted definition of axPsA and the lack of specific and validated outcome measures. Finally, poor data are available on the genetics of axPsA, although alleles differentially expressed in different patterns of axPsA might offer advantages in the prospective of personalized medicine in axPsA patients. Overall, this review suggests that there is an urgent need for more reliable evidence derived from studies specifically designed for axPsA and based on a validated definition of axPsA and on specific outcome measures.

Maria Maddalena Angioni,1 Alberto Floris,1 Ignazio Cangemi,1 Mattia Congia,1 Elisabetta Chessa,1 Sandro Orrù,2 Matteo Piga,1 Alberto Cauli1 1Rheumatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, University Clinic AOU, Cagliari, 09042, Italy; 2Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, 09042, ItalyCorrespondence: Maria Maddalena AngioniRheumatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, University Clinic AOU Cagliari, S.S. 554, Bivio per Sestu, Monserrato, Cagliari, 09042, ItalyTel +39 07051093340Email m.maddalena.angioni@gmail.comIntroduction: Psoriatic Arthritis (PsA) is a multifactorial disease, where the relative burden of genetic, epigenetic and environmental factors in clinical course and damage accrual is not yet definitively clarified. In clinical practice, there is a real need for useful candidate biomarkers in PsA diagnosis and disease progression, by exploring its underlying transcriptomic and epigenomic mechanisms. This work aims to profile the transcriptome in monozygotic (MZ) twins with psoriatic arthritis (PsA) highly concordant for clinical presentation, but discordant for the radiographic outcomes’ severity.Methods: We describe i) the clinical case of two MZ twins; ii) their comparative gene expression profiling (HTA 2.0 Affymetrix) and iii) signal pathways and pathophysiological processes in which differentially expressed genes are involved (in silico analysis by the IPA software, QIAGEN).Results: One hundred sixty-three transcripts and 36 coding genes (28 up and 8 down) were differentially expressed between twins, and in the brother with the most erosive form, the transcriptomic profiling highlights the overexpression of genes known to be involved in immunomodulatory processes and on a broad spectrum of PsA manifestations.Discussion: Twins’ clinical cases are still a gold mine in medical research: twin brothers are ideal experimental models in estimating the relative importance of genetic versus nongenetic components as determinants of complex phenotypes, non-Mendelian and multifactorial diseases as PsA.Keywords: psoriatic arthritis, gene expression profiling, diseases in twin, genetic, environment–gene interaction, joint erosions

Background: There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD). Methods: We conducted a network meta-analysis (NMA) in order to compare the effects of different treatments with the placebo on change in forced vital capacity (FVC), change in diffusion lung capacity for CO (DLCO), serious adverse events (SAEs), discontinuation for adverse events and mortality in SSc-ILD. Standardized mean difference (SMD) and log odds ratio were estimated using NMA with fixed effects. Results: Nine randomized clinical trials (926 participants) comparing eight interventions and the placebo for an average follow-up of one year were included. Compared to the placebo, only rituximab significantly reduced FVC decline (SMD (95% CI) = 1.00 (0.39 to 1.61)). Suitable data on FVC outcome for nintedanib were not available for the analysis. No treatments influenced DLCO. Safety and mortality were also not different across treatments and the placebo, although there were few reported events. Cyclophosphamide and pomalidomide were less tolerated than the placebo, mycophenolate, and nintedanib. Conclusion: Only rituximab significantly reduced lung function decline compared to the placebo. However, direct head-to-head comparison studies are required to confirm these findings and to better determine the safety profile of various treatments.

Identifying predictors of inadequate response to methotrexate (MTX) in rheumatoid arthritis (RA) is key to move from a “trial and error” to a “personalized medicine” treatment approach where patients less likely to adequately respond to MTX monotherapy could start combination therapy at an earlier stage. This study aimed to identify potential predictors of inadequate response to MTX in RA patients naïve to disease modifying anti-rheumatic drugs. Data from a real-life cohort of newly diagnosed RA patients starting MTX (baseline, T0) as first-line therapy were analyzed. Outcomes, assessed after 6 months (T1), were defined as failure to achieve a disease activity score 28 (DAS28) low disease activity (LDA) or a good/moderate response to MTX, according to the European League Against Rheumatism (EULAR) response criteria. Logistic regression was used to assess the associations between baseline variables and the study outcomes. Overall, 294 patients (60.5% females, median age 54.5 years) with a median disease duration of 7.9 months were recruited. At T1, 47.3% of subjects failed to achieve LDA, and 29.3% did not have any EULAR-response. In multivariate analysis, significant associations were observed between no LDA and current smoking (adjusted odds ratio [adjOR] 1.79, P = .037), female gender (adjOR 1.68, P = .048), and higher DAS28 (adjOR 1.31, P = .013); and between no EULAR-response and current smoking (adjOR: 2.04, P = .019), age (adjOR: 0.72 per 10-years increases, P = .001), and higher erythrocyte sedimentation rate (adjOR: 0.49; P = .020). By contrast, there were no associations between past smoker status and study outcomes. In summary, in our real-life cohort of disease modifying anti-rheumatic drug naïve RA patients, current smoking habit independently predicts inadequate response to MTX. This, together with other independent predictors of response to treatment identified in our study, might assist with personalized monitoring in RA patients. Further studies are required to investigate whether smoking quitting strategies enhance the therapeutic response to MTX.

Objective Metalloproteinase (MMP)-3 and MMP-12 are proteolytic enzymes especially implicated in joint inflammation. This study aims to evaluate their association with arthritis features and hand MRI abnormalities in patients with SLE. Methods Fifty SLE patients, with a mean (s.d.) age of 48.1 (14.6) years were tested for MMP-3 and MMP-12 serum levels, then further classified according to the presence of X-ray erosions and joint deformities. Eighteen RA patients aged 47.9 (11.8) and 14 healthy people aged 46.0 (11.0) were enrolled as control groups. A subgroup of 28 SLE patients underwent a dominant-hand MRI; the detected changes were classified and semi-quantitatively scored as capsular swelling, synovitis, edematous or proliferative tenosynovitis, bone oedema, bone erosions. Statistical analysis was performed using multiple regression models. Results MMP-3 were significantly higher in patients with Jaccoud’s arthropathy (JA) (22.1 ng/ml, P < 0.05) and independently associated with hsCRP serum levels (B-coeff 0.50; r = 0.30; P < 0.05). MMP-12 serum levels were significantly lower in patients with JA (0.18 ng/ml, P < 0.05) and inversely associated with the prednisone daily dose (B-coeff –0.03; r = −0.44; P < 0.01). Capsular swelling and edematous tenosynovitis, the most prevalent hand MRI changes in patients with JA, associated with higher MMP-3 (B-coeff 0.12; r = 0.66; P < 0.01 and B-coeff 0.08; r = 0.59; P < 0.01, respectively) and lower MMP-12 serum levels (B-coeff –7.4; r = −0.50; P < 0.05 and B-coeff –5.2; r = −0.44; P = 0.05, respectively). Conclusion Imbalanced MMP-3 and MMP-12 serum levels are influenced by inflammation and glucocorticoids in SLE patients and associated with JA and distinctive hand MRI changes.

Background The aim of this study was to evaluate the prevalence and clinical significance of Anti-neuronal antibodies (AnAb) in a cohort of neuropsychiatric (NP) Systemic Lupus Erythematosus (SLE) patients. Methods Overall, 28 SLE patients (age 45.6 ± 14.4 years) with inflammatory neuropsychiatric syndromes, classified according to existing criteria (1, 2) were enrolled and serum samples were collected before starting treatment for the specific NP event; 41 consecutive SLE patients (44.2 ± 14.2 years) without NP involvement, 22 Multiple Sclerosis patients (37.9 ± 11.0 years) and 82 healthy subjects (44.8 ± 15.0 years) served as controls. Search for AnAb was performed by tissue-based immunohistochemistry assays (IHC) on male Sprague Dawley rat’s brain sections and confirmed by cell-based immunocytochemistry assays on SH-SY5Y (human neuroblastoma) cell cultures. The association between serum positivity for AnAb by IHC and a large panel of data (demographic, serologic, SLEDAI, conventional brain MRI, treatment) was investigated by univariate analysis. Multivariate models were fitted with covariates with p Results AnAb were detected in 23 (82.1%) NPSLE patients and in 16 (39.0%) SLE patients without NP involvement resulting in 82% specificity (95%CI 71%-90%) and 61% sensitivity (95%CI 48%-72%) in differentiating NPSLE from SLE without NP involvement. None of the sera from MS patients (0%) and healthy subjects (0%) showed AnAb. Serum AnAb by IHC were independently associated with NPSLE (p Conclusion AnAb are significantly more frequent in patients with NPSLE than SLE. Further studies are needed to identify the unknown neuronal antigens targeted by AnAb in SLE patients.

Background/Purpose To compare the independent effect of achievement and maintenance of lupus low disease activity state (LLDAS) and clinical remission (CR) in preventing early damage accrual in the early stage of systemic lupus erythematosus (SLE) management. Methods In a monocentric inception cohort of 116 newly diagnosed SLE patients, LLDAS and CR achievement at 6 months (T1) after treatment initiation and their maintenance over the next 12 (T2) months were assessed. Early damage was assessed (T2) using the SLICC/damage index. Uni- and multivariate analysis were performed to evaluate the association of LLDAS and CR with early damage. Results LLDAS achievement was significantly more frequent than CR both at T1 (42.2% vs. 21.6%, p The overlap between persistent LLDAS and persistent CR between T1 and T2 was observed in 41.7% of cases. On multivariate analysis, the achievement of CR (OR 0.1, 95%CI 0.01–0.59, p=0.015) and LLDAS without CR (OR 0.2; 95%CI 0.06–0.99, p=0.049) at T1, as well as younger age at onset (OR 0.95, 95%CI 0.91–0.98, p=0.004), were negatively associated with early damage. Patients who achieved LLDAS at T1 and steadily persisted in this condition until T2 developed significantly less damage compared to those who failed to maintain it during the T1-T2 interval (p=0.003), those who achieved it later than T1 (p Conclusions Although CR is recommended as the primary treatment target in SLE, LLDAS may represent a valid alternative in the early stage of SLE management. LLDAS and CR maintenance should be targeted to prevent damage.

Objective To investigate risk factors for damage development in a prospective inception cohort of early diagnosed SLE patients. Methods The Early Lupus Project recruited an inception cohort of patients within 12 months of SLE classification (1997 ACR criteria). At enrolment and every 6 months thereafter, the SLICC/ACR Damage Index was recorded. The contribution of baseline and time-varying covariates to the development of damage, defined as any SLICC/ACR Damage Index increase from 0 to ≥1, was assessed using univariate analysis. Forward-backward Cox regression models were fitted with covariates with P Results Overall, 230 patients with a mean (s.d.) age of 36.5 (14.4) years were eligible for this study; the mean number of visits per patient was 5.3 (2.7). There were 51 (22.2%) patients with SLICC/ACR Damage Index ≥1 after 12 months, 59 (25.6%) after 24 months and 67 (29.1%) after 36 months. Dyslipidaemia [P = 0.001; hazard ratio (HR) 2.9; 95% CI 1.5, 5.6], older age (P = 0.001; HR 3.0; 95% CI 1.6, 5.5), number of organs/systems involved (P = 0.002; HR 1.4; 95% CI 1.1, 1.8) and cardiorespiratory involvement (P = 0.041; HR 1.9; 95% CI 1.0, 3.7) were independently associated with an increased risk of developing damage. Risk profiles for damage development differed for glucocorticoid-related and -unrelated damage. HCQ use (P = 0.005; HR 0.4; 95% CI 0.2, 0.8) reduced the risk of glucocorticoid-unrelated damage. Conclusion We identified risk factors of damage development, but little effect of glucocorticoids, in this early SLE cohort. Addressing modifiable risk factors from the time of SLE diagnosis might improve patient outcomes.

ObjectiveTo develop and validate the evidence-based and consensus-based Behçet’s Syndrome Overall Damage Index (BODI).MethodsStarting from 120 literature-retrieved preliminary items, the BODI underwent multiple Delphi rounds with an international multidisciplinary panel consisting of rheumatologists, internists, ophthalmologists, neurologists, and patient delegates until consensus was reached on the final content. The BODI was validated in a cross-sectional multicentre cohort of 228 patients with Behçet’s syndrome (BS) through the study of (a) correlation between BODI and Vasculitis Damage Index (VDI) and (b) correlation between BODI and disease activity measures (ie, Behçet’s Disease Current Activity Form (BDCAF), Physician Global Assessment (PGA), Patient Global Assessment (PtGA)), c) content and face validity and (d) feasibility.ResultsThe final BODI consists of 4 overarching principles and 46 unweighted-items grouped into 9 organ domains. It showed good to excellent reliability, with a mean Cohen’s k of 0.84 (95% CI 0.78 to 0.90) and a mean intra-class correlation coefficient of 0.88 (95% CI 0.80 to 0.95). Overall, 128 (56.1%) patients had a BODI score ≥1, with a median score of 1.0 (range 0–14). The BODI significantly correlated with the VDI (r=0.693, pConclusionsPending further validation, the BODI may be used to assess organ damage in patients with BS in the context of observational and controlled trials.

Demyelinating syndrome (DS) is a rare manifestation of systemic lupus erythematosus (SLE) (1%) with high clinical heterogeneity and potentially severe prognosis. It can represent a diagnostic and therapeutic challenge for clinicians. A recent study described 5 different patterns of demyelinating disease presentation, characterised by specific clinical, laboratory and brain and spine magnetic resonance imaging abnormalities: 1) neuromyelitis optica; 2) neuromyelitis optica spectrum disorders; 3) DS prevalently involving the brain; 4) DS prevalently involving the brainstem; 5) clinically isolated syndrome. In this review we briefly discuss typical characteristics of each DS presentation in SLE and we describe 5 illustrative clinical cases, one for each subset of DS, considering both diagnostic and therapeutic options.

Background:The most important goal of therapy in psoriatic arthritis (PsA) is to reach the remission state of disease. Nowadays, data on molecular players of clinical remission and effective disease inactivation are scarce: gene expression analysis could highlight markers characteristic of PsA remission state.Objectives:Our aim was to analyze the gene expression profile of patients with clinically inactive (drug-induced remission) PsA versus healthy controls and PsA active state.Methods:From a cohort of 300 patients affected by PsA according to CASPAR criteria, we selected 40 patients (peripheral arthritis subset) with >1-year remission by TNFα antagonism assessed by DAPSA ≤ 4 (R) and 40 PsA with active disease state by DAPSA > 14 score (no bDMARDs ongoing) (A), and 40 healthy controls (HC) matching for mean age and gender ratio. Both PsA groups were not on corticosteroid treatment. Each condition has been profiled first using pooled RNAs from peripheral blood (biological duplicates) by Affymetrix Human GeneChip HTA 2.0. To identify a transcript as differentially expressed in both duplicates, a fold change (FC) 1.5 and p-value 0.05 has been set. Then, from the comparative list of differential expressed genes (DEGs) in R vs HC state, coding mRNAs were selected and interactions analyzed by STRING software, biological functions and annotations by Gene Onthology (GO). From these analysis, 12 genes were validated in the whole PsA cohort (R+A) and HCs, by quantitative real-time PCR (RT-qPCR) in triplicate (TaqMan chemistry, GAPDH housekeeping, 2–ΔΔCt for relative quantification, FC cutoff ±1.5 for differential analysis).Results:The transcriptomic analysis generated 3 comparative lists of mRNAs (R vs HC= 125; R vs A= 1184; A vs HC= 378 transcripts). Then, we focused on remission state analyzing the mRNAs list R vs HC. Filtering data for coding DEGs, was made a list of 24 genes further analyzed for functions and interactions: STRING analysis created one interactions network and GO highlighted in which biological processes these DEGs are involved (Fig panels 1A, 1B). Validation analysis by rt-qPCR in the PsA cohort (R+A) and HCs confirmed the downregulation of c-FOS and the upregulation of CCDC50 (alias YMER) genes in the R vs HC conditions (pvalue= 0.004). The dysregulation of further genes in other comparisons was measured, as shown in Tab and Fig panel 1C.Conclusion:Observing the amount of DEGs, is evident that the drug-induced remission state is more similar to healthy condition, however this trend of “similarity” does not mean “identical”. The bioinformatic analysis showed that DEGs in the R vs HC conditions are primarily involved in biological processes related to immune system as well as correlates in an interactions network. Our molecular characterization of clinical remission revealed that effective disease inactivation appears to be molecularly-driven by two key genes, c-FOS and CCD50 (YMER), both involved in the NF-κB signalling pathway modulation.Coding DEGs mis-regulated in the remission state. Differentially expressed genes (DEGs) in the Remission (R) state vs Healthy Controls (HC) analyzed for multiple-proteins interaction by STRING software V10.5 (panel A) and biological functions by Gene Set Enrichment Analysis (panel B). DEGs validations by RT-qPCR, confirmed the CCD50 and c-FOS dysregulation in the R state (panel C, RQ= Relative Quantification, t test RvsHC pvalue=0,004).GENE SYMBOLGene chip Array R vs HCRemission vs HCActive vs HCRemission vs ActiveALPL-1.7-1.11.3-1.25ANPEP-1.681.01.1-1.1BPI-1.57-1.11.27-1.5CCDC501.51.5-1.251.8CEACAM8-2.3-1.21.2-1.5CHI3L1-1.59-1.1-1.0-1.0DEFA1B-2.3-1.41.9-2.7FCAR-1.56-1.11.1-1.3FOS-1.51-2.0-1.5-1.4KLRB11.52-1-1.61.6PADI2-1.54-1.11.0-1.1TNFSF14-1.511.11.2-1.1DEGs by RT-qPCR. Validated differentially expressed genes (DEGs) in the remission (R) state vs healthy controls (HC) selected from the microarray analysis comparative list (FC cutoff ±1.5). Differential analysis (40 R vs 40 HC vs 40 Active) was made by FoldChange (FC) cutoff ±1.5 (overexpressed ≥ 1.5; - 1.5 ≥ downregulated).Disclosure of Interests:None declared

Background:The Physician Global Assessment (PGA) is an outcome instrument based on physician judgement of disease activity in patients with Systemic Lupus Erythematosus (SLE). Due to the subjectivity of the score and lack of standardization, the PGA could represent a source of heterogeneity, because the same manifestations could be rated differently by physicians with different backgrounds (1).Objectives:The purpose of this study was to evaluate the inter-rater reliability of PGA between a rheumatology trainee and rheumatologists expert in SLE from 2 european countries.Methods:SLE patients classified according to SLICC 2012 criteria were enrolled between May 2019 and December 2019 during a SLEuro traineeship program. Demographic, clinical (SLEDAI-2k, PGA), serological and ongoing medication data were collected. PGA was evaluated before (pre-lab) and after (post-lab) knowledge of laboratory exams, using a Visual Analogue Scale (VAS) ranging from 0 to 3, anchored at point 1 (mild), 2 (moderate) and 3 (severe activity). A trainee in Rheumatology (EC) and three rheumatologists experts in SLE (LA, MP, FS) independently scored the PGA for each patient.The trainee preliminarily received a standardization training with her tutor (MP), consisting of a shared discussion about 10 consecutive SLE outpatients to increase reliability in PGA scoring.Inter-rater reliability was analysed using the intraclass correlation coefficient (ICC) with a two-way single-rating model (2,1); 95% confidence interval (CI) was calculated.Results:Fifty-seven patients (86% female) affected from SLE (29 belonging to a French cohort and 28 to an Italian cohort) with a mean (SD) age 43.2 (15.9) years and a median [IQR] disease duration 6.4 [2.0-15.4] years were enrolled. Clinical features are presented in table 1. Pre-lab PGA scores were obtained from all patients and ranged from 0 to 2.3; post-lab PGA scores were obtained from 51 patients and ranged from 0 to 2.9. Inter-rater reliability of the PGA among the trainee was good to excellent for each lupus expert comparison: a) pre-lab PGA ICC 0.94, 95% CI 0.87-0.97; post-lab PGA ICC 0.94, 95% CI 0.87-0.97 (MP); b) pre-lab PGA ICC 0.84, 95% CI 0.63-0.93; post-lab PGA ICC 0.96 CI 0.88-0.99 (LA); c) pre-lab PGA ICC 0.91, 95% CI 0.65-0.98; post-lab PGA ICC 0.91, 95% CI 0.65-0.98 (FS).Conclusion:After an adequate standardization, PGA scoring reaches good to excellent reliability between trainee and experts.References:[1]Chessa E, Piga M, Floris A, Devilliers H, Cauli A, Arnaud L. Use of Physician Global Assessment in systemic lupus erythematosus: a systematic review of its psychometric properties. Rheumatology (Oxford). 2020 Dec 1;59(12):3622-3632.Clinical DataCaucasian44 (77.2%)anti-dsDNA titre (median,IQR)14 (0-75)Hypocomplementemia (n,%)30 (54%)SLEDAI≥6 (n,%)18 (31.6%)SLEDAI (median,IQR)4 (2-6)Flares (n,%)18 (31.6%)Ongoing prednisone treatment (n,%)41 (71.9%)Prednisone dose mg (mean±sd)5 (0 - 8.9)Hydroxychloroquine (n,%)44 (77.2%)Immunosuppressant (n,%)35 (61.4%)Acknowledgements:Elisabetta Chessa gratefully acknowledges the SLEuro European Lupus Society for its financial support in her traineeship in Strasbourg.Disclosure of Interests:None declared

Demyelinating syndrome secondary to systemic lupus erythematosus (DS-SLE) is a rare encephalomyelitis burden with a high risk of disability and death. We report on a 49-year-old Caucasian woman with systemic lupus erythematosus (SLE) complicated by severe cognitive dysfunction, brainstem disease, cranial nerve palsies, weakness and numbness in limbs and multiple discrete magnetic resonance imaging (MRI) areas of damage within the white matter of semioval centers, temporal lobe, external capsule, claustrum, subinsular regions and midbrain. She also had multiple mononeuritis diagnosed through sensory and motor nerve conduction study. She was diagnosed with severe DS-SLE prominently involving the brain and was treated with 500 mg methylprednisolone (PRE) pulses for 3 consecutive days, followed by one single pulse of 500 mg cyclophosphamide, and 1 g rituximab, which was then repeated 14 days later. PRE 25 mg/day, rapidly tapered to 7.5 mg/day in 6 months, and mycophenolate mofetil 1 g/day were prescribed as maintenance therapy. She had progressive and sustained improvement in neurological symptoms with almost complete resolution of brain MRI lesions after 1 year. B-cell depleting therapy could be considered as a possible alternative to standard of care in the management of severe inflammatory neuropsychiatric SLE but it should be associated with a conventional immunosuppressant as maintenance treatment to reduce the risk of flare and reduce corticosteroids dose.

Objective To describe features of demyelinating syndrome (DS) in systemic lupus erythematosus (SLE). Methods A systematic review using a combination of Mesh terms in PubMed and a retrospective analysis of 343 adult patients with SLE were carried out to identify patients with DS. Retrieved cases were classified as affected with DS according to 1999 ACR nomenclature and attributed to SLE by applying the 2015 algorithm. DS defined according to the clinical but not temporal 1999 ACR criteria was classified as clinically isolated syndrome (CIS). Results Estimated prevalence of DS (including CIS) in the SLE cohort was 1.3% and incidence rate was 1.5 cases per 1000 patient-years. Overall, 100 cases from literature review and 4 from SLE cohort were identified and are presented as a whole: 49 (47.1%) were classified as neuromyelitis optica spectrum disorders (NMOSD), 29 (27.9%) as CIS, 14 (13.5%) as NMO, 7 (6.7%) as DS prominently involving the brainstem and 5 (4.8%) as DS prominently involving the brain. DS was the SLE onset manifestation in 41 (39.4%) patients. Longitudinally extensive transverse myelitis was the most frequent manifestations being present in 73 (70.2%) patients (37 NMOSD, 21 CIS, 14 NMO, 1 DSB). Methylprednisolone (79.8%) and cyclophosphamide (55.8%) pulses, but also plasma-exchange (16.3%) and rituximab (7.6%) in relapsing-refractory cases, were mostly prescribed. Complete recovery rate ranged between 62% in CIS to 7% in NMO. Conclusion DS in SLE is rare (1%) and encompasses different subtypes including CIS. Timely diagnosis and early treatment are recommended to minimize complications.

Background Remission is an important goal of therapy in psoriatic arthritis (PsA), but data on molecular players of clinical remission and effective disease inactivation are scarce. Gene expression profiling analysis could be useful to elucidate the pathogenic mechanisms of diseases, and differential gene expression analysis between diverse disease conditions produces gene signatures characteristic of the state or disease being studied. Objectives Our aim was to compare the transcriptional profiles of patients with clinically active versus inactive (remission state) PsA (peripheral joint subset), and healthy controls (HCs). Methods From a cohort of around 300 patients affected by PsA according to CASPAR criteria, we first selected 20 patients (peripheral arthritis subset) with active disease state (without biologic treatment ongoing) (A) and 20 patients with >1-year remission induced by TNFα antagonism (R), as assessed by DAPSA > 14, and DAPSA ≤ 4 scores respectively, and from 20 HCs matching for age and gender ratio. Both PsA groups were not on corticosteroid treatment. RNA from peripheral blood was extracted and, following quality analysis by Agilent Bioanalyzer, each condition has been profiled using RNAs pools in biological duplicates by distinct Affymetrix Human GeneChip HTA 2.0, for a total of 6 arrays. Data analysis was performed using the commercial software Partek Genomics Suite, V 6.6. To identify a transcript as differentially expressed, a value of fold change 1.5 and p-value 0.05 has been set. Results The Venn diagram shows all comparative groups (A vs R, A vs HC, R vs HC) with their relative amount of transcripts differentially expressed, generated using abovementioned parameters, and the relationship between sets (fig1, panel A). Using the list of transcripts differentially expressed in at least one of the aforementioned comparison, a hierarchical clustering was carried out to highlight the intra-condition expression profile. We have identified (arbitrarily) 4 clusters of transcripts with analogous transcriptional profile and to each of them a color code has been assigned (Heatmap in Fig1, panel B). For these clusters and for all lists of transcripts differentially expressed founded by our comparative study, we carried out the Gene Set Enrichment Analysis by Gene Ontology (GO), in order to identify how molecular functions, cellular components or biological processes occurs more frequently than expected in a reference list of transcripts. Conclusion Observing the amount of differentially expressed transcripts, is evident that while active disease state (A) has a clear-cut different profile, the drug-induced remission (R) is more similar with HCs condition. However, in the hierarchical clustering this trend of similarity does not appear in all clusters of transcripts, as shown particularly in the red, orange and green clusters. Again, the Gene Set Enrichment Analysis Score showed us that mRNA transcripts dysregulated in the R condition vs HCs, are involved in several biological processes related to immune system, development, response to stimulus, localization and others. Our next step will be to validate, by Real Time PCR in a large cohort of patients, the most interesting dysregulated genes covering biological functions eventually sustaining subclinical activity in PsA. Disclosure of Interests None declared

Background Disease activity evaluation is mandatory according to the OMERACT Core Set of Domains for Behcet’s Syndrome (BS). Poor data are available on Patient (PtGA) and physician (PGA) global assessment of disease activity in BS. Objectives To assess PtGA performance in patients with BS and how different disease manifestations influence the patient and physician’s perception of disease activity. Methods A multicenter cross-sectional cohort of consecutive BS patients was enrolled. Disease activity was evaluated by PtGA, PGA and the Behcet’s disease current activity form (BDCAF). PtGA and PGA were assessed trough a single question (“How active was BS during the last week?”) in a 10-cm visual analogic scale. Health related quality of life (HRQoL) perception was evaluated by the Physical Component Summary (PCS) and the Mental Component summary (MCS) of the SF36v2 questionnaire. Correlation between PtGA, PGA, BDCAF and between them and SF36v2 component summaries was assessed trough the Spearman’s correlation coefficient (rho). Two separated multiple regression models were built to measure the independent effect (β regression) of each active clinical manifestation on PtGA and PGA. Results Overall, 226 BS patients from 5 Mediterranean Countries were enrolled. Out of them, 111 (49.1%) were males and the median (IQR) age and disease duration were 46.9 (35.6-55.2) and 11.7 (5.9-20.8) years, respectively. The median (IQR) value of PtGA, PGA and BDCAF were 2.0 (0.3-5.0), 1.0 (0.0-3.0) and 3.0 (0.0-5.0), respectively. PtGA significantly correlated (Figure) with both PGA (rho 0.759. p 0.001) and MCS (rho -451. p > 0.001). Conclusion PtGA seems to be a valid outcome measure in BS and should be considered as a separate outcome measure or better be included in composite index for overall disease activity evaluation. Disclosure of Interests Alberto Floris: None declared, Matteo Piga: None declared, Gerard Espinosa: None declared, Nikolaos Kougkas: None declared, Andrea Lo Monaco: None declared, Giuseppe Lopalco Speakers bureau: SOBI, BMS, Ida Orlando: None declared, Vittorio Pirani: None declared, Ernestina Santos: None declared, Luisa Serpa Pinto: None declared, George Bertsias: None declared, Luca Cantarini: None declared, Alberto Cauli: None declared, Ricard Cervera: None declared, Joao Correia: None declared, Marcello Govoni: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Ana Martins da Silva: None declared, Piergiorgio Neri: None declared, Carlos Vasconcelos: None declared, Alessandro Mathieu: None declared

Background: Remission is an important goal of therapy in rheumatoid arthritis (RA), but data on molecular players of clinical remission and effective disease inactivation are scarce. Gene expression profiling analysis is useful to elucidate the pathogenic mechanisms of diseases, and differential gene expression analysis between diverse disease conditions produces gene signatures characteristic of the state or disease being studied. Objectives: Our aim was to compare the transcriptional profiles of patients with clinically active versus inactive (remission state) RA, and healthy controls (HCs). Methods: From a cohort of around 1000 patients affected by RA according to ACR-EULAR 2010 criteria, we first selected 20 patients with active disease state (without biologic treatment ongoing) (A) and 20 patients with >1-year remission induced by TNFα antagonism (Etanercept) (R), as assessed by DAS28(PCR) scores, and from 20 HCs matching for age and gender ratio. Both RA groups were not on corticosteroid treatment. RNA from peripheral blood was extracted and, following quality analysis by Agilent Bioanalyzer, each condition has been profiled using RNAs pools in biological duplicates by distinct Affymetrix Human GeneChip HTA 2.0, for a total of 6 arrays. Data analysis was performed using the commercial software Partek Genomics Suite, V 6.6. To identify a transcript as differentially expressed, a value of fold change 1.5 and p-value 0.05 has been set. Results: The Venn diagram shows all comparative groups (A vs R, A vs HC, R vs HC) with their relative amount of transcripts differentially expressed, generated using abovementioned parameters, and the relationship between sets (fig1, panel A). Using the list of transcripts differentially expressed in at least one of the aforementioned comparison, a hierarchical clustering was carried out to view the intra-condition expression profile. Here, we have identified (arbitrarily) 4 clusters of transcripts with analogous transcriptional profile and to each of them a color code has been assigned (Heatmap in Fig1, panel B). For these clusters and for all lists of transcripts differentially expressed founded by our comparative study, we carried out the Gene Set Enrichment Analysis by Gene Ontology (GO), in order to identify how molecular functions, cellular components or biological processes occurs more frequently than expected in a reference list of transcripts. Conclusion: Considering the amount of differentially expressed transcripts and the hierarchical clustering analysis, is evident that the drug-induced remission (R) is more similar with HCs condition, while active disease state (A) has a different profile; however “similar” profile does not mean “identical”. In fact, the Gene Set Enrichment Analysis Score showed us that mRNA transcripts dysregulated in the R condition vs HCs, are involved in several biological processes regarding the immune system, response to stimulus, biological regulation, locomotion and others. Our next step will be to validate, by Real Time PCR in a large cohort of patients, the most interesting dysregulated genes covering biological functions eventually sustaining disease activity. Disclosure of Interests: None declared

Background Irreversible organ damage is considered a core outcome by the OMERACT working group. However, no specific tools are currently available to detect and measure damage accrual in Behcet’s syndrome (BS). Objectives To develop and preliminarily validate the Behcet’s syndrome Overall Damage Index (BODI). NCT03803462. Methods A preliminary version of the instrument (p-BODI) was developed by reviewing pre-existing tools [e.g. Vasculitis damage index (VDI)] and through an extensive literature review. p-BODI was then reviewed and implemented by a multi-rounds Delphi process, involving an international and multidisciplinary (5 rheumatologists, 4 internist, 1 ophthalmologist, 1 neurologist) panel of experts in BS management and a patients’ delegate. A group of clinicians (CG), not involved in the BODI development, was asked to independently score a set of clinical vignettes, in order to test the instrument reliability, after a training process consisting of a user manual and a video-tutorial. Then, Cohen’s K and Intra-class correlation coefficient (ICC) between assessors and gold standard were calculated. Afterwards, BODI validation was conducted according to the OMERACT Filter 2.0 in a multicenter BS cohort. Results Starting from a list of 120 candidate items, the final version of BODI consisted of 4 overarching principles, 30 items and 12 sub-items (each of them scores one point) grouped in 8 domains (figure). In terms of reliability, the mean K coefficient was 0.84 (95%CI 0.78 to 0.90) and the ICC was 0.88 (95%CI 0.80-0.95). Validation cohort consisted of 228 BS patients (49.1% males), with a median (IQR) age and disease duration of 46.9 (35.5-55.0) and 11.7 (5.8-20.7) years, respectively. Overall, prevalence of any BODI damage (BODI ≥1) was 56.1% with a median score of 1.0 (0-2.0). In regard of construct validity, BODI score significantly correlated with VDI (Spearman’s rho 0.693, p Full agreement among the CG was reached in judging BODI as a credible, comprehensive, easy to use, timesaving and acceptable instrument. Conclusion BODI is the first tool specifically developed to assess damage in BS. Preliminary data encourage further validation of BODI in more extended and multi-ethnic BS cohorts before being applied in clinical practice and as a therapeutic outcome. Disclosure of Interests Matteo Piga: None declared, Alberto Floris: None declared, Gerard Espinosa: None declared, Nikolaos Kougkas: None declared, Andrea Lo Monaco: None declared, Giuseppe Lopalco Speakers bureau: SOBI, BMS, Ida Orlando: None declared, Vittorio Pirani: None declared, Ernestina Santos: None declared, Luisa Serpa Pinto: None declared, George Bertsias: None declared, Luca Cantarini: None declared, Alberto Cauli: None declared, Ricard Cervera: None declared, Joao Correia: None declared, Marcello Govoni: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Ana Martins da Silva: None declared, Piergiorgio Neri: None declared, Carlos Vasconcelos: None declared, Monica Muntoni: None declared, Alessandro Mathieu: None declared

Background Methotrexate (MTX) is the gold standard as first line treatment in rheumatoid arthritis (RA). Identifying predictors of response to MTX should be crucial in the view of a personalized therapy. Objectives To identify prevalence and potential clinical baseline predictors of inadequate response (IR) to MTX in RA patients naive to disease modifying anti-rheumatic drugs (DMARDs)*. Methods Data of 233 consecutive RA patients (according to ACR/EULAR 2010 criteria) naive to traditional and biologic DMARDs, attending the AOU University Clinic, Rheumatology Unit, Monserrato (Cagliari), Italy, were analyzed. Table 1 shows baseline demographic, clinical and serological characteristics of the cohort. Patients failing to reach low disease activity state (DAS 28 > 3.2) at 6 months (T1) since the beginning of MTX (T0) or patients undergoing therapeutic modification for persistently high disease activity (switch or addition of other traditional or biological DMARDs) before T1 were considered as IR. By univariate analysis, demographic, clinical and serological factors recorded at T0 were evaluated as potential predictors of IR at T1. Afterwards, factors with p Results At T1, 104 patients (44.6%) were classified as IR to MTX. In univariate analysis, factors significantly associated with IR were: female gender (69.2% vs. 54.3%; p=0.02), condition of ”current smoker” (22.1% vs. 10.9%; p=0.012), ESR [median (IQR): 30.0 (19.0-48.0) vs. 40.0 (25-62); p=0.035] and DAS28 (mean ± standard deviation: 5.5 ± 1.1 vs. 5.2 ± 1.3; p=0.037). High-titre positivity for RF and/or ACPA (57.3% vs. 45.9%; p=0.095) and high cumulative steroids dose [852 mg (300-1200) vs. 691 mg (0-150); p=0.071] were numerically higher in IR. In multivariate analysis, the ”current smoker” condition was confirmed as the only independent factor associated with IR to MTX after 6 months of treatment (OR: 2.333, 95% CI: 1.132-4.805; p=0.022). No significant association between ex-smoker status and IR to MTX was demonstrated. This result was confirmed even after stratification of ex-smokers over the time since smoking stop. Finally, for both current smokers and ex-smokers, the duration of exposure to cigarette smoking did not show any significant association with IR. Conclusion In this RA cohort, the condition of ”current smoker” was the only predictor of IR to MTX. This observation, together with the lack of association between previous smoking habit and IR to MTX, further prompt to recommend cessation of cigarette smoking in patients with RA who begin treatment with MTX. Acknowledgement This study was supported by an unconditioned Research grant from Pfizer Inc. Disclosure of Interests None declared

Background Colour Doppler sonography (CDS) is an emerging diagnostic tool for giant cell arteritis (GCA), however, its use in routine practice is still not widespread. Objectives To develop a protocol using CDS and explore its value in the routine care of patients with GCA. Methods We developed a structured scanning protocol for CDS of temporal and axillary arteries (total of 8 anatomical sites scanned per patient) based on previously published methods. We tested the protocol on consecutive patients referred to a single rheumatology centre, with suspected or established GCA, between July 2014 and September 2016. We defined a positive scan by the presence of halo in at least one branch of a temporal artery (TA) or one axillary artery (AX). We report data from the first 293 consecutively scanned cases. Results We assessed 293 patients (mean age 72±10, female/male 196/97), of whom 118 had clinically confirmed GCA. Amongst new referrals with confirmed diagnosis of GCA, 44% had a positive scan; two patients with a positive scan did not have GCA. 82% of new referrals patients showed exclusive TA involvement, 25% concomitant AX, and 4% exclusive AX involvement. High-dose glucocorticoid therapy had already been started in 78% of these patients for an average of 17±33 days. Amongst this group, the sensitivity of CDS was 46% (95% IC 37%>55%), specificity 98% (95% CI 93%>99.8%), positive predictive value 96% (88%>99.6%), and negative predictive value 60% (95% IC 52%>68%). During the period of observation, the rate of temporal artery biopsies (TAB) decreased significantly from 42% to 25% (p=0.002). During follow up, CDS was positive in 21% of 89 routine scans in asymptomatic individuals, compared to 58% in patients with confirmed clinical flares (45% of whom had negative inflammatory markers). Over time, the number of halos per patient reduced; only new or flaring patients showed a halo in >4 sites. Halo size at the TA did not change significantly (average thickness 0.6±0.1 mm), however, the size of AX artery halos significantly reduced from first referral (1.6±0.4 mm) to follow up (1.4±0.2, p=0.01) or during subsequent flares (1.4±0.2, p=0.02). Conclusions We have developed and tested a standardised methodology for CDS evaluation of GCA. CDS provides a high positive predictive value for a diagnosis of GCA in unselected patients from routine clinical practice, although prior high dose glucocorticoid therapy is likely to reduce its sensitivity. CDS allows for a significant reduction of TAB. We explored the role of CDS to detect disease flares and demonstrated a significant reduction in the extent of abnormalities, and of the size of halo of the AX arteries during follow up or flares. These findings could have a significant impact on the management of patients with suspected and confirmed GCA. Disclosure of Interest None declared

Patients with Systemic Lupus Erythematosus (SLE) may experience flare of disease activity. The aim of this study was to assess incidence, clinical features and predictors of flares, focusing on the relationship with serially assessed anti-double stranded DNA antibodies (anti-dsDNA) serum levels by Farr assay and pre-emptive therapeutic approaches of flares, through the analysis of a monocentric cohort of SLE patients and a literature review. Clinical and laboratory data of 120 out of 334 SLE patients, fulfilling inclusion criteria for enrolment and followed up between 1997 and 2012, were retrospectively collected. For the purposes of the study, a flare was defined as any new SLE manifestation or worsening of a pre-existing manifestation resulting in change of therapy. A review of the literature was performed searching for articles published between 1980 and 2015. Over a median (IQR) follow-up of 5.9 (3.0-8.9) years, 87 flares were recorded in 59 (49%) patients. The estimated incidence rate was 0.11 flare per patient-year, at the low-end of values reported in literature (0.19-1.76 patient-year). In our cohort, fluctuating anti-dsDNA serum levels were associated with flare development whereas precautionary change of therapy in presence of increased anti-dsDNA levels >50% was effective in preventing flares (p

Background In the view of applying a treat to target (T2T) strategy in the management of systemic lupus erythematosus (SLE), a novel definition of minimal acceptable disease activity – the lupus low disease activity state (LLDAS) [1] – and clinical remission (CR) [2] were recently proposed. Objectives To compare attainability and outcomes of LLDAS and CR as treatment targets in the early stages of SLE management. Methods LLDAS and CR prevalence were analysed at 6 (T1) and 18 (T2) months after treatment initiation (T0) in a monocentric cohort of 107 (median disease duration 9.7 months) prospectively followed Caucasian SLE patients. LLDAS was defined as SLE disease activity index 2000 (SLEDAI-2K)≤4 without major organ activity and no new disease activity, physician global assessment (0–3)≤1, prednisone ≤7.5 mg/day and well-tolerated immunosuppressant dosages. CR was defined as clinical SLEDAI-2K=0 (increased anti-dsDNA and low complement were excluded) and prednisone ≤5 mg/day in patients treated with/without stable immunosuppressants and/or antimalarials. Multivariate models were built to identify factors associated with failure to achieve LLDAS and CR, as well as to investigate relationship between the latter and early damage accrual (defined as SLICC/Damage Index≥1 at T2). Results LLDAS was achieved significantly more frequently than CR both at T1 [47 (43.9%) vs. 25 (23.4%); p Conclusions During the early stages of SLE, LLDAS and CR overlap definitely less frequently than reported in long-standing disease (53.2%–66.7% vs 83.9%–96.5% [2]). Although remission is recommended as the primary treatment target in SLE, LLDAS may represent a valid alternative in the first stages of disease management, being more attainable compared to CR and negatively associated to early damage. References [1] Franklyn K, et al. Ann Rheum Dis2016;75:1615–21. [2] Zen M, et al. Ann Rheum Dis2017;76:562–5. Disclosure of Interest None declared

Background Behcet's disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B*51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B*51. In fact, the HLA-B*51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes. Patients and methods In order to identify other genes of susceptibility to BD within the HLA region we investigated the distribution of human Allograft Inflammatory Factor-1 (AIF-1) gene variants among BD patients and healthy controls from Sardinia. Six (rs2736182; rs2259571; rs2269475; rs2857597; rs13195276; rs4711274) AIF-1 single nucleotide polymorphisms (SNPs) and related extended haplotypes have been investigated as well as their LD within the HLA region and with HLA-B*51. Overall, 64 BD patients, 43 HLA-B*51 positive healthy controls (HC) and 70 random HC were enrolled in the study. Results HLA-B*51 was the only allele with significantly higher frequency (pc = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571T AIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; pc = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B*51 and rs2259571G (pc = 9E-5), even though the rs2259571G distribution did not significantly differ between BD patients and HC. Conclusion No significant difference in distribution of AIF-1 SNPs haplotypes was observed between BD patients and HC and between HLA-B*51 positive BD patients and HLA-B*51 positive HC. Taken together, these results suggest that AIF-1 gene is not associated with susceptibility to BD in Sardinia.

Objective.Physician’s global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. This study assesses the reliability of the PGA, measured by means of 0–100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA).Methods.Sixteen centers from 8 countries enrolled 319 consecutive patients with PsA. PGA, PhysMSK, and PhysSk evaluation forms were administered at enrollment (W0) and after 1 week (W1). Detailed clinical data regarding musculoskeletal (MSK) manifestations, as well as dermatological assessment, were recorded.Results.Comparison of W0 and W1 scores showed no significant variation (intraclass correlation coefficients were PGA 0.87, PhysMSK 0.86, PhysSk 0.78), demonstrating the reliability of the instrument. PGA scores were dependent on PhysMSK and PhysSk (p < 0.0001) with a major effect of the MSK component (B = 0.69) compared to skin (B = 0.32). PhysMSK was correlated with the number of swollen joints, tender joints, and presence of dactylitis (p < 0.0001). PhysSk scores were correlated with the extent of skin psoriasis and by face, buttocks or intergluteal, and feet involvement (p < 0.0001). Finally, physician and patient assessments were compared showing frequent mismatch and a scattered dot plot: PGA versus patient’s global assessment (r = 0.36), PhysMSK versus patient MSK (r = 0.39), and PhysSk versus patient skin (r = 0.49).Conclusion.PGA assessed by means of VAS is a reliable tool to assess MSK and dermatological disease activity. PGA may diverge from patient self-evaluation. Because MSK and skin/nail disease activity may diverge, it is suggested that both PhysMSK and PhysSk are assessed.

Polymyalgia rheumatica (PMR) is an elderly onset syndrome characterised by aching and stiffness in the shoulders and the pelvic girdle associated to increased levels of acute phase reactants and rapid response to glucocorticoids.1 Although the cause of PMR remains unknown, most of the evidence suggest a multifactorial aetiology inducing an immunomediated pathogenesis.1 2 According to the ‘immunological continuum model’ proposed by McGonagle in 2006, all immune-mediated diseases can be conceptualised as predominantly autoinflammatory, predominantly autoimmune or mixed, on the basis of the relative contributions of innate and adaptive immune responses.3 Autoinflammatory diseases (AIDs) are characterised by tissue inflammation mainly due to aberrant activation of innate immune system without autoantibodies production and autoreactive T lymphocyte activation. In contrast, autoimmune diseases (ADs) are typically depicted by an abnormal activation of the adaptive immune system.4 However, the emerging understanding of the close linkage between innate and adaptive immunity led to consider the rare monogenic AIDs and ADs as the two opposite ends into a continuum of immune-mediated disorders, where middle entities are recognised (figure 1).3 Figure 1 Simplified classification of immune-mediated disease by McGonagle and McDermott.3 In the view of this background, we tried to envisage the most suitable place for PMR into the spectrum of the autoinflammatory/autoimmune disorders by reviewing and interpreting current evidence. Clear indication for a prevalent autoinflammatory background of PMR is related to the disease onset and course. Actually, starting of symptoms is generally over a few days or overnight in PMR,1 as well as in inflammatory periodic-recurring occurrence of AIDs,5 but in contrast to classic polygenic ADs where a subacute onset is frequently recorded (figure 2A).6 Further, after low-dose glucocorticoid therapy initiation, patients with PMR experience a rapid improvement of symptoms, generally within 24–72 hours, and more than 40% of them achieve …