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Objective To study subclinical inflammation in intercritical gout patients and its relation to the estimated size of monosodium urate crystal deposition and cardiovascular risk factors. Methods We performed a secretome analysis and the quantification of cytokine and adipokine plasma levels [IL-1β, IL-18, IL-6, soluble IL-6 receptor (sIL-6R), TNF-α, C-X-C motif chemokine 5, RANTES (Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted), leptin, resistin and adiponectin] to analyse subclinical inflammation in intercritical gout patients. Since it is currently not feasible to determinate the whole body deposit of monosodium urate crystals, we created an indirect clinical classification to estimate it. Then we compared cytokine levels in controls and gout patients and in patients with different crystal deposition sizes. We also studied the association between cytokine-levels and the number of cardiovascular risk factors. Results Ninety consecutive patients attending a crystal arthritis unit were studied. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in intercritical gout patients than in controls. An association was observed between IL-18, sIL6-R and RANTES levels and the size of crystal deposition. IL-18, sIL6-R, RANTES and leptin were higher in patients with no cardiovascular risk factors compared with controls with no risk factors. Conclusion Our results showed that the levels of some pro-inflammatory cytokines and metabolic proteins are elevated in intercritical gout patients. The levels of certain cytokines were related to the estimated size of the monosodium urate crystal deposition and to the number of cardiovascular risk factors. These cytokine changes may help to explain the increase in cardiovascular events in gout patients.

The prognosis of patients with rheumatoid arthritis (RA) has improved substantially in the last two decades due to the appearance of biological therapies, but above all, due to the improvement in the strategy and management of the disease. Our goal in RA should be to achieve remission, or in its absence, the lowest inflammatory activity. Achieving remission will prevent from structural and functional damage highly associated with RA itself. Clinical remission is defined as the absence of significant signs and symptoms of inflammatory disease activity, as well as the abrogation of any signs of systemic inflammation. Currently, there are some controversies about remission. Which is the real remission? Which remission criteria should be used and when? Does clinical remission mean ultrasound remission? In the present review, we try to answer and put some light into it, focusing on clinical and ultrasound deep remission.

Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms).

INTRODUCTION: To study metabolic signatures can be used to identify predictive biomarkers for a patient's therapeutic response. OBJECTIVES: We hypothesized that the characterization of a patients’ metabolic profile, utilizing one-dimensional nuclear magnetic resonance ((1)H-NMR), may predict a response to tocilizumab in patients with rheumatoid arthritis (RA). METHODS: 40 active RA patients meeting the 2010 ACR/EULAR classification criteria initiating treatment with tocilizumab were recruited. Clinical outcomes were determined at baseline, and after six and twelve months of treatment. EULAR response criteria at 6 and 12 months to categorize patients as responders and non-responders. Blood was collected at baseline and after six months of tocilizumab therapy. (1)H-NMR was used to acquire a spectra of plasma samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification. SPSS v.27 and MetaboAnalyst 4.0 were used for statistical and pathway analysis. RESULTS: Isobutyrate, 3-hydroxybutyrate, lysine, phenylalanine, sn-glycero-3-phosphocholine, tryptophan and tyrosine were significantly elevated in responders at the baseline. OPLS-DA at baseline partially discriminated between RA responders and non-responders. A multivariate diagnostic model showed that concentrations of 3-hydroxybutyrate and phenylalanine improved the ability to specifically predict responders classifying 77.1% of the patients correctly. At 6 months, levels of methylamine, sn-glycero-3-phosphocholine and tryptophan tended to still be low in non-responders. CONCLUSION: The relationship between plasma metabolic profiles and the clinical response to tocilizumab suggests that (1)H-NMR may be a promising tool for RA therapy optimization. More studies are needed to determine if metabolic profiling can predict the response to biological therapies in RA patients.

Introduction: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets. Methods: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study. Generated outcomes were presented at the 2020 OMERACT CPPD virtual Special Interest Group (SIG) meeting with discussion focused on whether different core domain sets should be developed for different calcium pyrophosphate deposition (CPPD) clinical presentations and how the future CPPD Core Domain Set may overlap with already established osteoarthritis (OA) domains. These discussions informed development of a future work plan for development of the OMERACT CPPD Core Domain Sets. Findings: Domains identified from a scoping review of 112 studies and a qualitative interview study of 36 people (28 patients with CPPD, 7 health care professionals, one stakeholder) were mapped to core areas of OMERACT Filter 2.1. The majority of SIG participants agreed there was need to develop separate core domain sets for "short term" and "long term" studies of CPPD. Although CPPD + OA is common and core domain sets for OA have been established, participants agreed that existing OA core domain sets should not influence the development of OMERACT core domain sets for CPPD. Prioritization exercises (using Delphi methodology) will consider 40 potential domains for short term studies of CPPD and 47 potential domains for long term studies of CPPD. Conclusion: Separate OMERACT CPPD Core Domain Sets will be developed for "short term" studies for an individ-ual flare of acute CPP crystal arthritis and for "long term" studies that may include participants with any clinical presentation of CPPD (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and/or CPPD + OA). (c) 2021 Elsevier Inc. All rights reserved.

Introduction: Although calcium pyrophosphate deposition (CPPD) disease is common, there are no validated outcome measures for clinical research in this condition. The aim of this study was to generate a list of outcome domains as reported by patients, their caregivers, healthcare professionals (HCPs) and stakeholders to inform the development of an Outcome Measures in Rheumatology (OMERACT) Core Domain Set for CPPD. Methods: Patients with CPPD and their caregivers, HCPs and stakeholders took part in semi-structured qualitative interviews to explore potential outcome domains for CPPD clinical research relevant to their lived experience and knowledge of CPPD. Interviews were conducted in six countries across three continents. Data was analysed using manifest content analysis to identify outcome domains, which were tabulated and mapped to the core areas as defined by the OMERACT Filter 2.1. Results: Thirty-six interviews were conducted in total. Participants comprised of 28 patients (six of which included a caregiver), seven HCPs and one stakeholder. The commonly identified (sub-) domains (d) across the 1) abnormalities/manifestations core area were joint pain (d = 35), joint swelling (d = 27), joint stiffness (d = 25), CPPD flares (d = 25); 2) life-impact core area were overall function (d=35), and specifically the ability to complete daily tasks (d = 25); and 3) societal/resource use core area were use of analgesic medicines (d = 26). Patients more commonly reported joint swelling, stiffness and range of movement, and use of analgesics while HCPs more commonly reported domains relating to presence of CPP crystals, radiologic calcification, joint damage, time to diagnosis and suitability of treatment. Conclusion: Among a number of potential outcome domains identified, articular manifestations, function and analgesic use were most frequently mentioned by participants. These findings will be used to develop an OMERACT Core Domain Set for CPPD. (C) 2021 Elsevier Inc. All rights reserved.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.

Background Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. Methods For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. Results The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). Conclusions The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA., This project was supported by UCB Pharma. The funders had no role in the study design, data analysis, data interpretation or writing the manuscript.

Objective: To explore the lived experience of people with calcium pyrophosphate deposition (CPPD) disease and the impact of this condition on their daily lives. Methods: Patients with CPPD and their caregivers were invited to take part in a one-to-one (patient only) or paired (patient and caregiver) semi-structured interview. Interviews covered patients' diagnosis and treat-ment experiences, and the impact of CPPD on their daily lives. Transcribed interviews were analysed using inductive thematic analysis. Results: 28 patient interviews, six of which included a caregiver, were conducted across five countries. Acute CPP crystal arthritis flares resulted in temporary but profound disability for most patients, disrupting their ability to go about day-to-day activities, and they sought immediate medical attention. CPPD+OA and chronic CPP crystal inflammatory arthritis presented patients with longer term limitations in daily lives. Patients and their caregivers described these disruptions and limitations, which included a reduced ability or inability to complete household and self-care tasks, exercise, socialise, work and drive. They also described how arthritis pain and resulting limitations adversely impacted upon patients' psychological wellbeing. Delays in referral to specialists and diagnostic uncertainty were described by many. Lack of appropriate treatment or access to treatments only upon worsening of symptoms impacted upon the length of time some patients spent in pain and with functional limitations. Conclusion: This study is the first to demonstrate the wide-ranging impact of CPPD, and highlights the need for improved diagnosis, physician training, as well as greater emphasis upon finding targeted therapies to specifically treat CPPD. (c) 2021 Elsevier Inc. All rights reserved.

Background: Different classification criteria for systemic lupus erythematosus (SLE) have been launched over the years. Our aim was to evaluate the performance of the EULAR/ACR-2019, SLICC-2012 and ACR-1997 classification criteria in a cohort of SLE patients with longstanding disease. Methods: Descriptive observational study in 79 patients with established and longstanding SLE. The three classification criteria sets were applied to those patients. Results: Of the 79 patients, 70 were women (88.6%), with a mean age of 51.8 ± 14 years and a mean disease duration of 15.2 ± 11.5 years. The sensitivity of the different criteria were: 51.9%, 87.3% and 86.1% for ACR-1997, SLICC-2012 and EULAR/ACR-2019, respectively. In total, 68 out of 79 patients (53.7%) met all three classification criteria, 11.4% did not meet any classification criteria and were characterized by low SLEDAI (0.6 ± 0.9), low SLICC/ACR Damage Index (0.88 ± 0.56) and fulfilling only skin domains, antiphospholipid antibodies or hypocomplementemia. To fulfill EULAR/ACR-2019 criteria was associated with low complement levels (p &lt, 0.04), high anti-dsDNA levels (p &lt, 0.001), presence of lupus nephritis III-IV (p &lt, 0.05) and arthritis (p &lt, 0.001). Conclusion: The EULAR/ACR-2019 classification criteria showed high sensitivity, similar to SLICC-2012, in SLE patients with longstanding disease. Patients with serological, articular or renal involvement are more likely to fulfill SLICC-2012 or EULAR/ACR-2019 criteria.

Blocking IL-6 pathways with sarilumab, a fully human anti-IL-6R antagonist may potentially curb the inflammatory storm of SARS-CoV2. In the present emergency scenario, we used "off-label"" sarilumab in 5 elderly patients in life-threatening condition not candidates to further active measures. We suggest that sarilumab can modulate severe COVID-19-associated Cytokine Release Syndrome."

Objectives: To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). Methods: All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. Results: 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]. Conclusion: Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics., BIOBADASER is supported by the Spanish Agency for Medicine and Health Products (AEMPS), Biogen, Bristol-Myers Squibb (BMS), Celltrion Healthcare, Lilly, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, and Samsung Bioepis.

Dear Editor, We read with interest the recent article by Singh and Cleveland on the hypersensitivity risk of allopurinol (ALP) and febuxostat (FBX) compared with colchicine.1 A common challenge when using ALP, linked to hypersensitivity reactions, is the potential development of cutaneous adverse reactions (CARs). Most are often mild, non-specific rashes; however, severe CARs, including Stevens-Johnson syndrome (SJS), may occur, but with a low incidence (0.69 cases per 1000 person-years) in non-Asian populations.2 In the EuroSCARs study, ALP was the reason for 5% of all severe CARs.3 So, FBX is often chosen as urate-lowering agent on the background of an ALP-related CAR. However, these patients were not eligible for the pivotal trials of FBX4 and were excluded from the recent analysis by Singh and Cleveland.1 Therefore, the accurate rate of FBX-related CARs in patients who previously suffered from ALP, and the mechanisms behind, remain undetermined to date. We have …

Introduction To determine patient and rheumatologist preferences for rheumatoid arthritis (RA) treatment attributes in Spain and to evaluate their attitude towards shared decision-making (SDM). Methods Observational, descriptive, exploratory and cross-sectional study based on a discrete choice experiment (DCE). To identify the attributes and their levels, a literature review and two focus groups (patients [P] = 5; rheumatologists [R] = 4) were undertaken. Seven attributes with 2–4 levels were presented in eight scenarios. Attribute utility and relative importance (RI) were assessed using a conditional logit model. Patient preferences for SDM were assessed using an ad hoc questionnaire. Results Ninety rheumatologists [52.2% women; mean years of experience 18.1 (SD: 9.0); seeing an average of 24.4 RA patients/week (SD: 15.3)] and 137 RA patients [mean age: 47.5 years (SD: 10.7); 84.0% women; mean time since diagnosis of RA: 14.2 years (SD: 11.8) and time in treatment: 13.2 years (SD: 11.2), mean HAQ score 1.2 (SD: 0.7)] participated in the study. In terms of RI, rheumatologists and RA patients viewed: time with optimal QoL: R: 23.41%/P: 35.05%; substantial symptom improvement: R: 13.15%/P: 3.62%; time to onset of treatment action: R: 16.24%/P: 13.56%; severe adverse events: R: 10.89%/P: 11.20%; mild adverse events: R: 4.16%/P: 0.91%; mode of administration: R: 25.23%/P: 25.00%; and added cost: R: 6.93%/P: 10.66%. Nearly 73% of RA patients were involved in treatment decision-making to a greater or lesser extent; however, 27.4% did not participate at all. Conclusion Both for rheumatologists and patients, the top three decision-making drivers are time with optimal quality, treatment mode of administration and time to onset of action, although in different ranking order. Patients were willing to be more involved in the treatment decision-making process. Electronic supplementary material The online version of this article (10.1007/s12325-020-01258-5) contains supplementary material, which is available to authorized users.

This project was supported by Arthritis New Zealand (grant reference R259 to WJT). The US data collection was funded by Pfizer (undertaken commercially by Adelphi Values). The NZ data collection was supported by the Maaori Gout Action Group of Counties Manukau District Health Board and the Auckland Rheumatology Fund (to KL). The Spanish data were collected with the direct support of the authors. The funders had no direct role in the conduct of the reported study, analysis of the data or writing of the manuscript. The International Classification of Functioning, Disability and Health (ICF) aims to comprehensively describe the ways in which a person's health condition affects their life. This study aimed to contribute to the development of an ICF core set for gout through patient opinion derived from focus groups and interviews. We conducted a secondary qualitative analysis of data from three studies investigating the patient experience of gout. In total there were 30 individual interviews and 2 focus groups (N = 17) comprising 47 participants. We conducted thematic analysis of the textual data to extract meaning units, which were then linked to the ICF. A large number of ICF categories were relevant to patients with gout. Participants mentioned 93 third level categories, 17 of which were mentioned by more than 50% of patients. The most references for a single category was for b280, Sensation of pain, followed by personal factors (not yet categorised by the ICF). The most participants mentioned the environmental factor e355, Health professional support, followed by b280, Sensation of pain. The categories identified in this study as relevant to patients with gout highlight the severe pain associated with this disease, the impact on mobility and corresponding life areas. The roles of health professional support, medication, and personal attitudes to disease management are also reflected in the data. These results will contribute to the development of the ICF core set for gout.

The aim of this study was to assess changes in the estimated glomerular filtration rate (eGFR) in gouty patients with chronic kidney disease (CKD) using a "treat-to-target" (T2T) approach in gout. This multicenter observational retrospective study included patients diagnosed with gout and CKD stage 3 taking xanthine oxidase inhibitors (XOIs) (allopurinol or febuxostat) for at least 12 months. All patients were treated using a T2T strategy according to national gout guidelines to achieve the target levels of serum uric acid (sUA; < 5-6 mg/dl) within 6 months of the first visit. The primary outcome was to assess changes in eGFR. The effects of independent variables were analyzed over eGFR in a linear mixed-effects (LME) model. Fifty patients with gout and CKD stage 3 treated with XOIs with a T2T strategy for 12 months were included. Eighty-two percent of the patients achieved the sUA target during the study period. The improvement seen in eGFR was higher during the first 6 months, showing a median increase of 7.54 ml/min/m(2) (SE = 1.25) and trending towards stability over 12 months. For every 1 mg/dl of decrease in sUA, an improvement of 1.5 ml/min/m(2) in eGFR was observed (coefficient +/- SE: - 1.58 +/- 0.26) (p < 0.001) with no differences between type and dosage of XOIs treatment, colchicine administration, age, sex, and smoking status. A reduction in sUA levels using a T2T approach with XOIs at an optimal dose is possible and could help conserve and improve renal function in gouty patients with CKD stage 3.

IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses.Heparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients.Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups.RA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.

Background:Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease of unknown etiology. Tocilizumab (TCZ) is a first-line biological disease-modifying anti-rheumatic drug (bDMARD) which inhibits Interleukin 6 (IL-6) pathway through blockade of its receptor. At present, there is a lack of evidence to recommend the treatment of one bDMARD over another.(1) Seeking for genetic biomarkers to predict response to treatment could be key towards a personalized treatment strategy in rheumatology.(2)Objectives:We aimed to evaluate whether functional single nucleotide polymorphisms (SNPs) in the IL6R gene could predict response and/or toxicity to TZC in Caucasian patients diagnosed with RA.Methods:Retrospective analytical preliminar study of a cohort of 31 patients diagnosed with RA (ACR/EULAR 2010 criteria) who received treatment with TCZ within the last 10 years. Epidemiological, clinical and laboratory data were collected. DNA was extracted from EDTA blood samples. Three SNPs in the IL-6 receptor gene (rs12083537, rs2228145, rs4329505) were genotyped by real-time PCR with TaqMan probes. The associations between polymorphisms and clinicopathological features were evaluated using parametric tests. Efficacy was assessed as the difference of DAS-28 CRP at 6 months. The toxicities recorded were hepatotoxicity, infections, hypersensibility, gastrointestinal, hematological and dyslipidemia.Results:The 31 DNA samples from patients included were mainly female (83.9%) and had a mean age at diagnosis of 46.8 years. The mean duration of treatment was 51.3 months and, previously to initiate TCZ, they received a mean of 2,6 csDMARD and 1,7 bDMARD.The more frequent adverse effects were hypertransaminasemia (22.6%) and neutropenia (32.3%). Most relevant epidemiologic and clinical data is shown in Table 1.Table 1.Clinical characteristics. RA=Rheumatoid Arthritis. CCP= anti-Cyclic Citrullinated Peptides. RF=Rheumatoid factor. csDMARDs= conventional synthetic Disease-modifying antirheumatic drug. bDMARD= biological Disease-modifying antirheumatic drug. BMI=Body Mass Index. Sc=subcutaneous. Ev=endovenous. DAS28= Disease Activity Score in 28 jointsSex (n=31), n (% women/men) 26/5 (83,9%/16,1%)Age at diagnosis (n=31), years +- SD 46,8+- 12,8Erosive RA (n=31), n(%) 14 (45,2%)Anti-CCP positive (n=31), n(%)UI+- SD 23 (74,2%)259,7 +- 137,3RF positive (n=31), n (%)UI+-SD 21 (67,7%)189,4+- 114Previous csDMARD (n=31), n°+-SD2,6 +-1,3Previous bDMARD (n=31), n°+- SD1,7 +- 1,4BMI (n=29), mean +- SD29,3+- 5,1Duration of treatment (n=31), months +-SD51,3 +- 36,3-Active treatment (n=12)-80,9+- 18,3-Finished treatment (n=19)-32,6+- 32,2Route of administration (n=31), n (%) sc/ev 11/20 (35,5/64,5)Basal DAS28 (n=30), mean+- SD5,3 +- 1,1DAS28 reduction at 6 months (n=28), mean+-SD2,9 +-1,1The univariate analyses showed that the rs2228145 variant was statistically associated with differences in DAS28 reduction at 6 months (p=0.042). Regarding efficacy, we also found a trend with the SNP rs4329505 (p=0.173), which could achieve statistical significance with the projected inclusion of more patients. No associations were found regarding adverse effects.Conclusion:The rs2228145 polymorphisms in the IL6R gene may be considered as a pharmacogenetic biomarker of TCZ response in RA patients. More studies are required in order to investigate the clinical use of pharmacogenetic biomarkers in rheumatic diseases.References:[1]Smolen, Josef S., Robert B., et al. 2020. “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2019 Update.” Annals of the Rheumatic Diseases 79 (6): 685–99.[2]Tarnowski, Maciej, Agnieszka Paradowska-Gorycka, et al. 2016. “The Effect of Gene Polymorphisms on Patient Responses to Rheumatoid Arthritis Therapy.” Expert Opinion on Drug Metabolism & Toxicology 12 (1): 41–55.Disclosure of Interests:None declared

Background:Gout is the most common inflammatory arthritis in adults. It is caused by the chronic deposition of monosodium urate crystals in joints. Hypertension, diabetes mellitus, chronic kidney disease (CKD) and cardiovascular disease are highly prevalent in gout patients.Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids or colchicine are the first line therapeutic agents for flares. These drugs can be contraindicated in a large group of gout patients. Off label prescription of IL-1 receptor blockage with anakinra can be an alternative for this complex patients.Objectives:The main objective of this study is to perform a scoping review about patient characteristics, comorbidity, effectivity and safety profile of patients with gout treated with anakinra.Methods:A total of 1119 citations were screened. The reviewers performed a two-stage screening by title/abstract and full-text screening. Thirty six articles that finally met selection criteria, were included for data extraction and synthesis. Treatment duration of ≥12 weeks was considered chronic.Results:Four hundred forty three patients were included in the study. 20 patients (4,5%) received chronic treatment and 423 (95,5%) flare treatment. Outcomes from 496 flares were finally analyzed.The mean age of the patients was 63.6 years and 84% were men. The clinical presentation was polyarticular in 47.9% and tophaceous gout in 66.5%. Some of these patients presented atypical forms of the disease such as spinal gout, autoinflammatory syndromes or sternoclavicular joint arthritis.Most of the patients presented comorbidities, the most prevalent being arterial hypertension in 127 (70.5%) and chronic kidney disease (≥ 3 stage) in 220 (51.8%). History of transplant in 37 (14.6%) with stem cell, kidney, heart, and liver transplant. More than half of patients had more than one associated comorbidity. Demographic and clinical characteristics of gouty arthritis patients are presented in Table 1. Flare was present in admitted patients in 260 (57.5%). Anakinra was administered in 52 patients with an active infection.Different treatment regimens were described. Daily administration was used in 98% of the patients. 92.8% of the flares were treated seven days or less, being the three days regimen the most prevalent. In the chronic group the longest treatment reported was 5 years.Efficacy of treatment with anakinra was evidenced, in flare 426 patients (93%) and chronic 19 patients (91%). Overall, anakinra was well tolerated. In the case of flares, thirty-three (7.9%) adverse effects related to anakinra administration were registered: seven (1.6%) site injection reactions, five (1.1%) reversible hematological alterations and five acute infections (H1N1, herpes zoster, severe cold, pulmonary abscess and nosocomial pyelonephritis). In chronic treated patients, adverse infectious events were more prevalent, seven (32%) infections (Staphylococcus aureus tophus (2), Staphylococcus aureus lung abscess, erysipela of the leg, Streptococcus B urinary tract infection, Staphylococcus aureus knee arthritis and tuberculous cervical lymphadenitis).Conclusion:Anakinra has been shown to be effective and safe in treatment for flares in gout complex or resistant patients. It has been shown in multiples scenarios like active infections, dialysis, transplants, chronic kidney disease, tophi and polyarticular disease refractory to standard treatment. It has also shown its effectiveness as chronic treatment, but there are more concerns about its safety. These findings need to be confirmed with controlled clinical trials for anakinra inclusion in treatment recommendations in special situations of flares in complex or resistant gout patients.Disclosure of Interests:None declared.

Background:Cryoglobulinemia (CG) is a rare phenomenon, which is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate in vitro at less than 37°C and dissolve when the temperature rises again. Is related to hematological disorders, infections and autoimmunes diseases.Objectives:To describe the differential clinical features, serological and demographics in a cohort of patients diagnosed with CG.Methods:We describe a retrospective cohort of 252 cryoglobulin (Cg) positive samples, obtained from a database from the immunology laboratory of a tertiary hospital (November 2018-November 2019). We obtained 182 patients with CG, classified according to their etiology into 4 groups: 1)Rheumatic diseases (RD) that includes rheumatoid arthritis, Systemic lupus erythematosus, Sjögren´s syndrome and Systemic scleroderma, 2)Hepatotropic viruses (HV) with patients diagnosed with Hepatitis C virus, B virus and both, 3)Hematological diseases (HD) and 4)Essential cryoglobulinemia (CGE). Demographic variables, clinical and serological data were collected. A comparative analysis was performed with the Mann-Whitney U test and the multivariate Kruskal-Wallis test, nonparametric variables were compared using a Wilcoxon test. Ten patients, with more than one disease from 4 groups, were excluded from the study.Results:Out of 182 reviewed patients, 172 were included in the study. Mean age at diagnosis was 59.7(±14.0). Demographic, clinical and laboratory characteristics are described in table 1. Mixed CG was the predominant subtype, in 116 (67.4%) patients. The most prevalent CG-associated diseases were HV infection with 91(53%) patients. CGE mostly presented with cutaneous manifestations (p=0.0001), particularly purpura. In RD group the presence of Raynaud and non-erosive arthritis (p=0.0001) was relevant. Laboratory findings showed that CG titration varies according to the etiology, being HD the one with the highest values with 292.2 (±546.2). There is significant difference in terms of the average of rheumatoid factor (RF) being higher in the group by CGE. On other hand, the group HV presented more consumption of complement, and showed the lowest average p=0.0001, without more severe clinical manifestations.RD (n=47)HV (n=91)HD (n=17)CGE (n=17)Gender,n(%) F42 (89.4)57 (62.6)7 (41.2)11 (64.7)Age at dg, years, (± SD)60.6 (±14)59.6 (±13.1)61.1(±16.6)56.3(±20.8)p=0.8CLINICAL CHARACTERISTICSSkin n (%)18 (38.3)10 (11.0)2 (11.8)9 (52.9)pRaynaud n (%)14 (29.8)1 (5.9)3 (17.6)pPurpura n (%)6 (12.8)9 (9.9)2 (11.8)6 (35.3)p=0.04Acrocyanosis n (%)6 (12.8)1 (5.9)p=0.0033Ulcers n (%)3 (6.4)2 (2.2) -2 (11.8)p=0.19Peripheric Neuro n (%)10 (21.3)9 (9.9)1 (5.9)4 (23.5)p=0.13N-E arthritis n (%)22 (46.8)8 (8.8)1 (5.9)4 (23.5)pGMN n (%)5 (10.6)3 (3.3)1 (5.9)3 (17.6)p=0.11LABORATORYCg (mg/dL) x (± SD)26.7 (±63.2)65.8 (±256.5)292.4 (±546.2)47.59 (±79.1)pIsotype IgG, n (%)G+M 26 (55.3)G+M 72 (79.1)M 8 (47.1)G+M 12 (70.6)β2M (≥1.8 mg/L), n (%)7/40 (17.5%)1/5 (20.0%)3/12 (25.0%)-p= 0.44RCP (mg/L) p 5010.3 (±26.2)3.9 (±3.0)13.4 (±18.3)8.5 (±12.0)p= 0.47ESR (mm/h) p5040.0 (±28.5)20.3 (±20.2)35.4 (±35.1)24.5 (±25.0)p= 0.0003RF + (>20UI/mL), n (%)19/46 (41.3)44/86 (51.2)5/11 (45.5)7/17 (41.2)p= 0.09p5090.6 (±175.9)161.0 (±219.5)94.8 (±135.6)284.5 (±619.3)pC3 ()20 (42.6)47 (51.6)3 (17.6)3 (17.6)p= 0.13x (± SD)90.1 (±28.6)68.5 (±10.8)99.1 (±29.0)114.8 (±12.7)pC4 ()17 (36.2)36 (39.6) -3 (17.6)p= 0.02x (± SD)15.6 (±9.0)7.6 (±3.5)20.4 (±7.4)21.1 (±9.5)pConclusion:In our cohort, not all patients with CG presented clinical manifestations being those associated with CGE and RD those with the highest skin and joint expression. The most prevalent association of CG continues to be the HV and we confirmed the characteristic decrease in C3 and C4 complement levels, together with the positivity for RF.Disclosure of Interests:None declared

Background:Patients with autoimmune inflammatory rheumatic diseases (AIIRD) have a higher burden of infectious diseases compared to the general population. This could be explained by the disturbances in their immune system response, comorbidities and immunosuppressive treatment.Vaccination is the most effective measure to prevent infections.Objectives:To describe a cohort of patients with AIIRD referred to the infectious disease´s unit according to the vaccination protocol.Methods:Restrospective and descriptive study of a cohort of 286 patients with AIIRD who were evaluated in the rheumatology service of a tertiary hospital in Barcelona and referred to the infectious disease´s unit according to the vaccination protocol among 1 year,between January 1rst December 31st, 2019. The vaccination protocol included serologies of human immunodeficiency virus,hepatitis A,B and C, varicella zoster,tuberculosis,measles,mumps and rubella virus.The recommended vaccines were H.influenzae b,S.pneumonia,influenza,hepatitis A and B(immunity absence),meningococcus c,tetanus – diphtheria (low antigenic load),poliomyelitis and human papillomavirus (not vaccinated).The patients included were diagnosed with a rheumatologic condition under immunosuppressive therapy. Demographic variables,diagnosis,treatment,vaccines administered,infections and adverse effects were collected.Results:Of 286 patients reviewed the mean age was 61, 4 (±14.4) years. The characteristics of the cohort are shown in Table 1. Most of the patients used csDMARDs 149 (52.1%), 77(26.9%) patients used combined treatment. Measles and rubella are part of the triple virus vaccines included in the systematic Spanish vaccination schedule, in our cohort 20 (7%) patients had negative serologies for measles and 26 (9%) for rubella. 57 (20%) patients had latent TB with positive Quantiferon.Forty-one (14.3%) were vaccinated before receiving immunosuppressive treatment. The less administered vaccine was influenza with 44.9% (vaccination rate in Spain in healthy population, in 2019-2020 was 51.2%).No serious adverse effects were reported in relation to the vaccination. The infectious complications during the follow-up period were bronchopneumonia in a patient with RA treated with certolizumab (1), herpes zoster infection in RA on adalimumab(1), recurrent otitis in RA on adalimumab(1), mycobacterium avium infection in RA on etanercept(1), TB reactivation in RA with GCs and csDMARDs(1) and Papilloma virus infection in SpA on ustekinumab (1).Table 1.CHARACTERISTICS OF COHORT OF PATIENTSSex n % (women/men)193/93 (67,5/32,5)Age, years ± DE61.4 ± 14.4Diagnoses AIIRD, n (%)Rheumatoid arthritis n (%)164 (57.3)Systemic lupus erythematosus n (%)6 (2.1)Sjögren´s syndrome n (%)9 (3.1)Systemic sclerosis n (%)1 (0.35)Inflammatory myopathie n (%)5 (1.7)Vasculitis n (%)36 (12.6)Polymyalgia rheumatica n (%)4 (1.4)Spondyloarthropathy n (%)46 (16.1)Others n (%)15 (5.2)Treatment AIIRDGCs n (%)116 (40.7)csDMARDs n (%)149 (52.1)bDMARDs n (%)80 (27.8)tsDMARDs n (%)7 (2.4)Others1 n (%)12 (4.2)GCs + csDMARDs n (%)59 (21)GCs + bDMARDs n (%)14 (4.9)GCs + csDMARDs + bDMARDs n (%)4 (1.4)VaccinesPCV 13 n (%)283 (99)PPSV23 n (%)265 (93)HiB n (%)265 (93)NM n (%)247 (86.7)Influenza n (%)128 (44.9)HBV n (%)121 (42.3)Vaccination before IS n (%)41 (14.3)Vaccination with IS n (%)244 (85.3)Other: Behcet,Adult Stills,Relapsing polychondritis,IGg4 related disease,SarcoidosisOthers1: Mycophenolic acid,cyclosporine and tacrolimusConclusion:In our cohort, the vaccination protocol proved to be a good tool to improve the vaccination rate of rheumatological patients, despite this, the vaccination of Hepatitis B and specially of influenza, continues to have a lower prevalence to general population.The vaccines were effective since none of the preventable infections occurred during follow up, despite the use of an immunosuppressant. Vaccination showed a good safety profile, without reported serious adverse effects or worsening of the underlying disease.Disclosure of Interests:None declared

Background:Gout is the most prevalent inflammatory arthritis. Gout is chronic inflammatory deposition disease related to an increase of cardiovascular (CV) events and mortality. Subclinical chronic inflammation has been demonstrated in this patients but not its relation with the monosodium urate (MSU) crystal deposit size and the number of CV risk factors.Objectives:To study the subclinical inflammation in intercritical gout patients and its possible relation to the estimated size of the crystal deposition and the number of CV risk factors.Methods:To analyze subclinical inflammation we performed a secretome analysis and a cytokine and adiponektine plasma levels quantification (IL-1β, IL-18, IL-6, sIL-6R, TNFα, CXCL-5, RANTES, leptin, resistin and adiponectin) in a cohort of gout patients. As nowadays it is not feasible to determinate the whole body deposit of MSU crystals we created three different MSU crystal deposit size patient groups using an indirect clinical and analytical classification to estimate it. Then we compared cytokine levels between healthy donors and gout patients. We also compared cytokine levels between the different crystal size deposition groups and studied its association to the number of CV risk factors.Results:Ninety consecutive patients attending a Crystal Arthritis Unit were studied. Mean age was 68.27 (28-101) years. 81.1% were male. Clinical gout evolution was of 10.1±9.8 years. 77.5% were on urate lowering treatment. 24% had tophaceous gout. Mean uric acid was 6.3±2.1 mg/dl with 47.1% of them being on target. Hypertension was present in 68.9%, diabetes mellitus in 18.9%, dislipemia in 48.9%, BMI>30 in 32.9%, abdominal obesity in 50% and 16.1% suffered from ischemic heart disease. From the 102 molecules studied in the secretome analysis in 56 there was at least a 20% difference between donors group and any of the deposition groups. In 74% of them gout patients secreted lower levels. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in patients than in healthy donors. IL-18, sIL6-R, RANTES and CXCL5 levels were associated to the size of the crystal deposits. IL-18, sIL-6R, RANTES and leptin were higher in gout groups with CV risk factors. IL-18, sIL6-R, RANTES and leptin were higher in gout patients with no risk factors when compared to healthy donors with no risk factors. We found no differences when comparing urate lowering treated and non-treated patients.Conclusion:Our results demonstrate that some proinflammatory cytokines and metabolic proteins are raised in intercritical gout patients. Some of them are different from the flare/inflammasome expected ones. In some cytokines this elevation is related to the size of the monosodium urate crystal deposit and/or to the number of cardiovascular risk factors. This cytokine changes could help to explain the increase of the cardiovascular events in gout patients.Disclosure of Interests:Cesar Diaz-Torne Grant/research support from: Received a grant from Grünenthal, Maria Angels Ortiz: None declared, Sicylle Jeria Navarro: None declared, Andrea Garcia-Gullien: None declared, Lluis Sainz: None declared, Hector Corominas: None declared, Silvia Vidal: None declared

Background:Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia.Objectives:We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends.Methods:We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening.Results:45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age >51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; pConclusion:sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use.References:[1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5.[2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020.[3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519.Disclosure of Interests:None declared.

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease with variable clinical features and a complex physiopathology. In 2019, EULAR and ACR have jointly developed new classification criteria with both high sensitivity and specificity. These criteria have the particularity of including the presence of ANA as an obligatory entry criterion and the existence of clinical and immunological domains with weighted scores.Objectives:To evaluate the performance and characteristics of the ACR/EULAR 2019, SLICC 2012 and ACR 1997 classification criteria in a cohort of SLE patients with longstanding disease.Methods:Descriptive observational study that enrolled a cohort of SLE patients with longstanding disease followed in a tertiary level hospital. Demographic and clinical data were gathered along with the fulfillment of classification criteria. The sensitivity of each classification criteria and the statistically significant associations between criteria fulfillment and clinical and immunological data were calculated. Statistical analyses were performed using the Chi2, T-student and ANOVA tests. Statistical significance was assumed in p values Results:A total of 79 patients (88.6% women) with a mean age of 51.8±14 years, disease duration of 15.2±11.5 years and SLEDAI of 2.65±2.1 were included. The sensitivity of the different classification criteria was 51.9% for ACR 1997, 87.3% for SLICC 2012 and 86.1% for ACR/EULAR 2019 (Table 1).Table 1.Sensitivity and average scores.ACR/EULAR 2019SLICC 2012ACR 1997Sensitivity (%)86.187.351.9Average score of patients classified as SLE(±SD)18.6±5.85.3±1.45±0.9Average score of patients NOT classified as SLE(±SD)6.1±2.52.8±0.42.8±0.851.9% of patients met all three classification criteria, 29.1% met SLICC 2012 and ACR/EULAR 2019, 5% only met SLICC 2012 and 3.7% exclusively met ACR/EULAR 2019. 11.4% of patients did not meet any classification criteria and were characterized by having a low SLEDAI (0.6±0.9) and fulfilling only skin domains (alopecia or oral ulcers), antiphospholipid antibodies or hypocomplementemia.Statistically significant associations were found between meeting ACR/EULAR 2019 classification criteria and the presence of low C3 and C4 (pIn the SLICC 2012 evaluation, significant associations were found between meeting these criteria and the presence of arthritis (pFullfilment of ACR 1997 was associated to the presence of malar rash (pThe Kappa concordance coefficient among classification criteria is detailed in Table 2.Table 2.Kappa concordance coefficient.ACR/EULAR 2019 - SLICC 2012ACR/EULAR 2019 - ACR 1997SLICC 2012 - ACR 1997Kappa concordance coefficient0.610.270.30Conclusion:The ACR/EULAR 2019 classification criteria maintain a high sensitivity similar to the SLICC 2012 in SLE patients with longstanding disease, both of which are much higher than ACR 1997. Patients with serological, articular or renal involvement are more likely to meet SLICC 2012 or ACR/EULAR 2019 criteria. It is noteworthy the relevance of dermatological manifestations in ACR1997 classification criteria against the increased weight that a better understanding of SLE physiopathology has provided to analytic and immunological criteria in the subsequent classification criteria.Disclosure of Interests:David Lobo Prat: None declared, Berta Magallares: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, HyeSang Park: None declared, Patricia Moya: None declared, Ignasi Gich: None declared, Ana Laiz: None declared, Cesar Díaz-Torné: None declared, Ana Milena Millán Arciniegas: None declared, Susana P. Fernandez-Sanchez: None declared, Hector Corominas: None declared

Background Immune checkpoint inhibitors (ICI) against CTLA-4 or PD-1/PD-L1 improve the survival of patients with advanced malignancies including melanoma, lung cancer among other tumours. Because of its mechanism of action, ICI are prone to produce different immune-related adverse events (irAEs), including musculo-skeletal manifestations. Objectives Our aim was to describe the experience with rheumatic irAEs in two tertiary centres. Methods All adult patients referred to the Rheumatology department from 2015 to 2018 because of the onset of musculo-skeletal symptoms following treatment with an ICI were included. Data collected comprised demographic features as well as ICI indication and type, history of rheumatic disease, disease manifestations at irAE onset, laboratory tests, ultrasound findings and treatment. Diagnostic and treatment approach was done according clinical judgment and in a daily clinical practice setting. Results 20 patients were included, 50% female, with a mean age of 61,5 years (range 32-83). The indication for ICI was melanoma in 10 cases, lung cancer in 5, urothelial neoplasia in 2 and squamous skin, breast and head and neck cancer in 1 case each. Pembrolizumab was the most used ICI accounting for 9 cases (1 combined with epacadostat), 8 patients were treated with Nivolumab (4 combined with Ipilimumab), 2 wit Atezolizumab (1 combined with Ibatasertib) and 1 Ipilimumab in monotherapy. A history of previous rheumatic disease was reported in 8 patients (1 seropositive RA, 1 Spondyloarthritis, 1 SLE, 1 gout, 1 chondrocalcinosis, 1 fibromyalgia, 1 De Quervain tendinitis, 1 hand osteoarthritis) and 1 had psoriasis. The most frequent irAE presentation was arthritis with 8 cases (40%), arthralgia in 4 cases (20%), 1 case of myalgia, 2 presented PMR-like symptoms, 1 tenosynovitis and 2 paraesthesia (1 with associated dysesthesia). After assessment, 7 patients were diagnosed as undifferentiated arthritis, 1 leukocytoclastic vasculitis, 1 small-vessel vasculitis, 2 psoriatic-like arthritis, 1 tenosynovitis, 2 PMR and 6 were classified as having non-inflammatory symptoms. Antibody status was analyzed in 16 patients. Anticitrullinated-peptide antibodies, rheumatoid factor and HLA B27 were negative in all cases (except for 1 patient with seropositive RA), ANAs were positive in 4 (including 1 patient with previous SLE) but without any specificities (i.e. ENAs) and ANCA were negative in one case with small-vessel vasculitis. Ultrasound assessment was performed in 6 patients, 3 presented synovial hypertrophy with positive power Doppler (1 with tenosynovitis associated), 1 peritendinous fluid collection, 1 elbow joint effusion and 1 bilateral supraspinatus calcified tendinopathy. Most patients were treated with glucocorticoids 12 (60%) and NSAID 6 (30%) and only 3 patients had to discontinue ICI treatment due to irAEs. Conclusion Our results were in line with previous studies showing that musculo-skeletal irAEs associated to ICI may present as a flare of a previous known rheumatic disease or as a de novo symptom. Most patients presented with asymmetric mono or oligoarthritis having a good response to GC and NSAID without the need of adding DMARD or withdraw of ICI therapy.. Disclosure of Interests Sebastian C Rodriguez-Garcia: None declared, DAVID LOBO: None declared, Raul Castellanos-Moreira Speakers bureau: MSD, Lilly, Ana Milena Millan Arciniegas: None declared, Roberto Gumucio: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Virginia Ruiz-Esquide Speakers bureau: Sanofi, Lilly, MSD, Berta Magallares: None declared, Cesar Diaz-Torne: None declared, Patricia Moya: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Hector Corominas: None declared, Jose A. Gomez-Puerta Consultant for: Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen, MSD, Pfizer, Roche

Background: Allopurinol is first-line urate-lowering drug (ULD) for patients with gout. However, around 10% of them refer adverse events, often at skin, which can be severe. Febuxostat is a non-purine selective xanthine oxidase inhibitor, often a therapeutic alternative in this setting, though data regarding safety in those patients with previous cutaneous adverse reactions (CAR) to allopurinol is still limited. Some cases and small retrospective series have reported skin adverse events under both allopurinol and febuxostat. Objectives: To assess the cutaneous safety of febuxostat when used in patients with previous skin reactions to allopurinol. Methods: A multicentre retrospective, descriptive study performed in seven Rheumatology units around Spain. Crystal-proven gout patients with previous CAR to allopurinol and treatment with febuxostat were selected. Demographic (age, gender), clinical (skin events, liver disease, concomitant thiazides) and laboratory variables (serum urate (SU), glomerular filtration rate) were collected. The primary study variable was the rate of patients developing CAR also with febuxostat. A descriptive analysis with estimation of 95% confidence interval (95%CI) is presented. Results: Sixty-seven gout patients with prior allopurinol-related CAR treated with febuxostat were enrolled. Their average age was 68.1 years (SD±14.8), being 49 males (73.1%). Thirteen of them were under thiazide treatment (19.4%) and average glomerular filtration rate was 66.1 ml/min (±24.3) when allopurinol was started, at a median dose of allopurinol of 100 mg/day (IQR 50-300) and mean SU of 8.9 mg/dl (±1.7). The reported CAR under allopurinol were nonspecific in 55 (82.1%), maculopapular rash in 9 (13.4%), and Stevens-Johnson’s syndrome in 3 (4.5%).. Out of 67 patients, 10 developed CAR with febuxostat (14.9%; 95%CI 8.3-25.3%): nonspecific in 8 cases, one case of maculopapular rash and other of Stevens-Johnson’s syndrome. Median (IQR) glomerular filtration rate, starting dose of febuxostat and SU level were 69.5 (42-87.8), 80 mg/day (40-80) and 8.2 mg/dl (7.15-9.14), respectively. Benzbromarone was initiated in all 10 patients with CAR to both allopurinol and febuxostat, and only one developed a nonspecific rash. Conclusion: In this multicentre study, around 15% of patients with prior allopurinol-related CARs also developed them with febuxostat. Further prospective and intervention studies are needed to confirm these results, though caution is recommended when using febuxostat in this subgroup of patients. Disclosure of Interests: Neus Quilis Marti: None declared, Paloma Vela-Casasempere Grant/research support from: UCB, Abbvie, Pfizer, Roche, Bristol-Myer-Squibb (another research, not BIOBADASER related), Consultant for: UCB, Lilly, Pfizer, Roche, Bristol-Myer-Squibb, Speakers bureau: Roche, UCB, MSD, Pfizer, GSK, BMS, Lilly, Boris Anthony Blanco Caceres: None declared, Cesar Diaz Torne Consultant for: Grunenthal, Speakers bureau: Grunenthal, Enrique Calvo-Aranda Speakers bureau: Gruhnental, SOBI, Menarini, Francisca Sivera: None declared, Alejandro Prada-Ojeda: None declared, Fernando Perez-Ruiz Grant/research support from: Asociacion reumatologos de Cruces, Consultant for: Grunenthal Horizon Menarini, Speakers bureau: Grunenthal, Menarini, Fundacion Espanola Reumatologia, Eliseo Pascual Consultant for: Eliseo Pascual has participated in the boards of Astra Zeneca, Menarini, Grunenthal and Horizon, Speakers bureau: speaking fees from Astra Zeneca and Grunenthal, Mariano Andres: None declared

Background: Polymyalgia rheumatica (PMR) is characterized by pain in the shoulders and hips, elevation of acute phase reactants and a rapid response to treatment with corticosteroids. Currently, there is no specific test for its diagnosis, and it presents a wide differential diagnosis. Positron Emission Tomography - Computed tomography (PET-CT) is a non-invasive technique, capable of measuring metabolic activity by locating and quantifying glucose consumption. The use of PET-CT in the study of neoplastic, infectious or inflammatory processes suggests that it may be a suitable technique for the study of the differential diagnosis of patients with PMR. It is unknown if there are differences in the result of the technique in patients with debut PMR vs. patients with cortico-resistant PMR. Objectives: To describe the findings of PET-CT in patients with PMR. To analyze if there are significant differences between the results of patients with onset PMR and those of cortico-resistant PMR patients. Methods: This is a cross-sectional prospective study performed in a cohort of patients with PMR. Out of all patients with PMR who do follow up treatment in our centre, the patients selected for this study included those who underwent a PET scan at the time of diagnosis and those who presented corticosteroid resistance (patients who did not respond to conventional therapy with corticosteroids or with a relapse with doses For the categorical variables, the chi-square test or Fisher’s exact test were used, as appropriate. In the case of quantitative variables, we used the comparison of the mean values, by means of a ”t” test. The level of statistical significance was established for those values of p Results: 103 patients with a PMR diagnosis who had undergone a PET-TC were included, out of the total number of patients that we visited in our service. 52 (50.4%) patients had an onset PMR and 51 (49.9%) had PMR refractory to treatment. The demographic, clinical and serological characteristics of the patients at the time of PET-CT are shown in Table 1. The PET-CT showed a distribution of uptake compatible with the diagnosis of PMR in 73 (70.9%) patients, vasculitis of large vessels in 16 (15%) and contributed in the diagnosis of neoplastic processes in 5 (4.8%). Table 2 shows the final diagnoses. When analyzing the results of PET in patients with onset PMR vs. those who are corticosteroids resistant, no significant differences were observed in the final diagnoses (p = 0.078). Conclusion: PET-CT confirms the diagnosis of PMR in the significant majority of patients included in the study. In this cohort, PET-CT allowed to diagnose vasculitis of large vessels and neoplasms in 16% and 5% of the patients respectively. We did not observe differences in the PET findings in those patients who underwent a PET at the time of diagnosis vs. those who are corticosteroid resistant. References: [1] Ann Nucl Med. 2018 Oct;32(8):573-577; [2] Semin Nucl Med. 2017 Jul;47(4):408-424; [3] Br J Radiol. 2017 Aug;90(1076):20170198 Disclosure of Interests: Maria Emilia Corica: None declared, Patricia Moya: None declared, Alejandro Fernandez: None declared, Berta Magallares: None declared, Ignasi Gich: None declared, Ana Milena Millan Arciniegas: None declared, HyeSang Park: None declared, Monica Paola Sarmiento: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Cesar Diaz-Torne: None declared, Josep Maria Llobet: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Hector Corominas: None declared

Background: The presence of antineutrophil cytoplasmic antibodies (ANCA) in systemic sclerosis (SSc) has been described rarely. The series published in the literature are scarce1 Its role in the evolution on the disease is unknown Objectives: To describe the epidemiological and clinical characteristics of ANCA positive patients from a cohort of patients with SSc Methods: Retrospective observational descriptive study in a cohort of 312 SSc. We analyzed those patients who were positive for ANCA, collecting variables: gender, race, age, age at diagnosis of SSc, at onset of symptoms, type and immunological profile, clinical manifestations of SSc, association with other systemic autoimmune diseases (SAD), capillaroscopic findings, and treatment. Regarding the ANCA profile, pattern, specificity and titration, as the time of evolution of SSc until the appearance of ANCA Results: Four of 312 patients with SSc had ANCA (prevalence = 1.28%). All were women and 2 had perinuclear pattern. The reason to request ANCA was kidney failure with proteinuria in 2 cases. One patient developed anti-myeloperoxidase (MPO) renal vasculitis and biopsy showed segmental glomerular necrosis and extracapillary proliferation. Other had proteinuria with hematuria without renal failure and biopsy with glomeruli in wafer. Regarding clinical manifestations all ANCA had some degree pulmonary disease 3 interstitial lung disease (ILD)1 pulmonary arterial hypertension (PAH) confirmed by right heart catheterization (KT). Three had SAD associated Characteristics of the sample in table 1 Conclusion: In our cohort the presence of positive ANCA was associated with renal vasculitis in one case. All patients with ANCA had vascular or interstitial pulmonary involvement, as well as other associated SADs. Further studies are needed to characterize the clinical associations of the presence of ANCA in SSc References [1] J Rheumatol21:864–870 [2] Rheumatol Int (2006) 26: 369–375 Disclosure of Interests: Sycille Jeria: None declared, HyeSang Park: None declared, Andrea Garcia-Guillen: None declared, DAVID LOBO: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Berta Magallares: None declared, Patricia Moya: None declared, Ana Milena Millan Arciniegas: None declared, Cesar Diaz-Torne: None declared, Susana P. Fernandez-Sanchez: None declared, Hector Corominas: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND

Background: Minor salivary gland biopsy (MSGB) is the most important diagnostic test of Sjogren’s Syndrome (SS). It demonstrates the presence of the inflammatory infiltration in the most affected site. It’s possible role as a biomarker in the disease is still unknown. The Inmunology Department of our center conducts a detailed analysis of the MSGB about the leukocyte infiltration and quantifies number of each cell. Objectives: To describe the inmunologic features of the MSGB and carry out an association analysis with clinical variables Methods: Clinical variables, ESSDAI index at the moment of diagnosis and laboratory parameters were recorded. As from the MSGB, number of infiltration focus (1, 2 or several), big infiltrations (>100 cells), number of B and T cells, CD4/CD8 ratio and presence of isolated lymphocyte were collected. Categorical variables were described as frequencies and analysed using Fisher exact test. T student and Wilcoxon Rank Sum Test were used for comparison of means (μ). Results: In 2017, a total of 104 MSGB were carried out in our center. Among them 58 were diagnosed as SS by medical and ACR/EULAR 2016 criteria. Finally 41 patients with SS and abnormal MSGB result were included for this study. Biopsy: Patients with active disease (ESSDAI≥2) had greater amount of cells (μ 159 cells vs 509 cells; p=0,055) as well as those with extraglandular disease (μ 160 vs 488; p=0.08). Patients with active disease also had larger number of infiltration focus (p= 0.062). The presence of isolated CD8+ T cells was observed in 13 patients and they had lesser cells (μ 136 vs 381; p=0.35). In those samples with predominance of T cells over B cells had larger number of infiltrate focus (7/20; 35% vs 12/21; 57.14%; p=0.155). No association with disease activity or extraglandular manifestation was found. Extraglandular manifestation and disease activity: 18 patients had extraglandular disease. Moderate or severe ESSDAI activity was found in 14 of these patients (34.2%, p=0.00). The biopsy of patients with extraglandular disease had larger amount of cells (μ 200 vs 145; p=0.01). Patients with active disease had more infiltratre focus (6/22 vs 11/19; p=0.047). Disease evolution time was similar with a mean duration of 8-9 years in both groups. Corticosteroids: There were 3 patients with active steroid treatment (≥prednisone 10mg/d) at the moment of the biopsy. All 3 of them had >1 focus in the sample and 2 of them had large infiltrate with >150 cells. Eight of them had received steroids in the last 5 years, 6 of them had large infiltate with >150 cells and 4 had >1 infiltrate focus in the biopsy. A study with more sample should be carried out to study the influence of steroids in the biopsy results. Conclusion: Patients with extraglandular disease have larger amount of cells in the composition of infiltration. Those with more disease activity had more number of infiltration focus. In 14 patients specific antibodies and antinuclear antibodies were negative. In these patients the biopsy is the most useful diagnostic test. Possible association of those variables that were statistically not signifcant should not be ruled out due to the small sample size of the study. Disclosure of Interests: HYE SANG PARK: None declared, LAURA MARTINEZ-MARTINEZ: None declared, Berta Magallares: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000 USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Cesar Diaz-Torne: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Patricia Moya: None declared, Ana Milena Millan Arciniegas: None declared, Andrea Garcia-Guillen: None declared, Sycille Jeria: None declared, DAVID LOBO: None declared, Susana P. Fernandez-Sanchez: None declared, CONXITA PITARCH: None declared, MANEL RIERA: None declared, MARIA CARMEN HERNANDEZ LAFUENTE: None declared, Candido Juarez: None declared, Hector Corominas: None declared

Background: The antibody against the transcriptional intermediate factor 1γ (Anti-TIF1γ or anti-p155), is considered specific for dermatomyositis (DM) and its a marker of cancer risk. Our center carries out the determination of anti-TIF1γ by a homemade immunoblot (IB) technique with a 155 kDa TIF1γ human recombinant protein (OriGene). Currently there is a commercial technique of IB to detect TIF1γ (Euroimmun), however, commercial kits sometimes elaborate antigens without using whole protein structure. To date, there are no studies that study the agreement between the commercial kit and homemades IB. Objectives: 1-To compare the commercial IB results of anti-TIF1γ with homemade IB. 2-To describe and compare the clinical characteristics of the patients analyzed by both techniques. METHODS: Observational retrospective study that included adult patients with some determination of anti-TIF1γ antibodies since 2014 in two tertiary-level university hospitals. We collected demographic and clinical data of all patients. Taking into account their diagnoses we grouped them into: Cancer associated Myositis (CAM), DM without cancer, Systemic autoimmune Diseases (SAD) non-DM and other diagnoses. Subsequently, the clinical agreement with the IB results of anti-TIF1γ performed by commercial (cIB) and homemade (hIB) technique were analyzed. A p value RESULTS: 48 patients were recruited (77.1% women). 13 had diagnosis of CAM, 19 of DM without cancer, 7 of other non-DM EAS, and 9 had other diagnoses. Of all DM (CAM and DM without cancer), 12 were positive for both techniques. 5 presented discordant results (4 hIB positive with negative cIB and 1 cIB positive with negative hIB). 15 DM were negative for the two techniques, of which 8/15 had other antibodies associated with autoimmune Myopathy (3 NXP-2, 1 Mi2, 1 MDA5, 1 SAE, 1 Jo1 and 1 Ro52). When we analyzed patients with CAM with both techniques, 10/13 presented positive hIB vs 8/13 cIB positive. DM without cancer, 6/19 had positive hIB vs 5/19 cIB positive. The sensitivity and specificity of each test was evaluated in CAM and DM without cancer, being 61.5% and 73.7% respectively for cIB (p = 0.071), compared to 76.9% and 68.4% for hIB (p = 0.029). In non-DM SAD group, 1 patient had positive determination for both techniques, 3 had positive cIB with negative hIB, and 3 cIB negative with positive hIB. We also found other antibodies in 6/7 patients with non-DM SAD. The 9 patients with other diagnoses were: 1 positive for both techniques and 8 positive for cIB and negative for hIB. CONCLUSIONS: Homemade IB with 155 kDa recombinant protein was superior to cIB to detect TIFγ in our serie of patients with CAM. This could have clinical implications in screening and early detection of neoplasia that affect false negative by cIB. A positive cIB in patients not suspected as a SAD were negative for hIB in the major part of cases. It would be recommended to check the commercial IB using homemade IB, due to its known clinical-therapeutic implications. Disclosure of interests: Ana Milena Millan arciniegas: None declared, M. ANGELES MARTINEZ: None declared, aNAIS MARISCAL: None declared, aNDRES BAUCELLS: None declared, Leticia alserawan: None declared, Ernesto Trallero: None declared, Cesar Diaz-Torne: None declared, ana Laiz Consultant for: Lilly, Novartis, abbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, abvvie, MSD, UCB and Janssen, Berta Magallares: None declared, Patricia Moya: None declared, HyeSang Park: None declared, andrea Garcia-Guillen: None declared, Sycille Jeria: None declared, DAVID LOBO: None declared, albert Gil: None declared, Coral Gozalvez: None declared, Susana P. Fernandez-Sanchez: None declared, Laura Martinez-Martinez: None declared, Esther Moga: None declared, Hector Corominas: None declared, Candido Juarez: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, albert Selva-O’Callaghan: None declared

Background: In the last years multiple genetic variants have been associated with autoimmune disease (AD) risk. However, much less is known on the association with important environmental factors like diet. Objectives: The objective of the present study is to characterize the dietary patterns of six prevalent ADs, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE). Methods: A cross-sectional cohort of 11,621 individuals from Spain encompassing 1,949 RA, 2,186 psoriasis (PS), 1,437 PsA, 699 SLE, 1,415 ulcerative colitis (UC), 1,952 Crohn’s disease (CD) and 1,983 healthy controls, was recruited by the IMID-Consortium. The weekly consumption frequency of main food categories was recorded, together with drinking habits and smoking status. Multivariate linear models were used to test for association while adjusting for confounders. Results: Patients with AD targeting the digestive system showed the largest differences in comparison to controls. In the rheumatic ADs several food categories were also found to be consumed differently compared to controls. SLE had a high consumption of sweets and pastries, and RA ate more fruit and bread/wholegrain foods and less meat and cold cuts compared to controls. In PsA the dietary pattern differences with controls where milder, and non-overlapping with psoriasis. Disease activity was significantly associated with specific food categories in CD, UC and PS, mildly in RA and SLE, and PsA showed no association. High smoking cessation rates were observed in UC, CD and SLE, but not in Ps, RA and PsA. Tea/coffee and alcohol consumption was low in all ADs compared to controls. Conclusion: Our results show previously unreported associations with dietary habits in rheumatic ADs. Disclosure of Interests: Antonio Julia: None declared, Sergio Hilario Martinez: None declared, Jesus Tornero: None declared, Juan D. Canete: None declared, Antonio Fernandez-Nebro: None declared, Francisco Blanco: None declared, Jesus Rodriguez: None declared, Francisco J Lopez-Longo: None declared, Benjamin Fernandez-Gutierrez: None declared, Jordi Gratacos: None declared, Jose Javier Perez Venegas: None declared, Carolina Perez: None declared, Ruben Queiro Silva: None declared, Alejandro Olive: None declared, Mercedes Alperi-Lopez: None declared, Carlos A. Montilla-Morales: None declared, Jose Luis Andreu: None declared, Juan Carlos Torre-Alonso: None declared, M Angeles Aguirre-Zamorano: None declared, Hector Corominas: None declared, Paloma Vela Casasempere: None declared, Victor Martinez Taboada : None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Joan Miquel Nolla: None declared, Isidoro Gonzalez-Alvaro: None declared, Santiago Munoz-Fernandez: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen, Carlos M. Gonzalez: None declared, Antonio Zea: None declared, Maria Lopez Lasanta: None declared, Daniel Roig: None declared, Jose M Pego-Reigosa: None declared, Mireia Lopez Corbeto: None declared, Pedro Zarco-Montejo: None declared, Mercedes Freire Gonzalez: None declared, Alba Erra: None declared, Elvira Diez Alvarez: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Esther Rodriguez Almaraz: None declared, Alicia Garcia: None declared, Patricia Carreira: None declared, GEORGINA SALVADOR ALARCON: None declared, Cesar Diaz Torne Consultant for: Grunenthal, Speakers bureau: Grunenthal, Ricardo Blanco: None declared, Alfredo Willisch Dominguez: None declared, Jose Antonio Mosquera Martinez: None declared, Simon Sanchez Fernandez: None declared, Julio Ramirez: None declared, Sara Marsal: None declared

With the aim to develop and validate a clinical + ultrasound (US) inflammation score in rheumatoid arthritis (RA) for use in clinical practice, a mixed-method study was conducted. The theoretical development of the index was achieved with qualitative methodology (discussion group and Delphi survey). Subsequently, a cross-sectional study was carried out to analyse issues related to scoring and validation of the new index. RA patients underwent clinical [28 swollen and tender joints count, patient and physician global assessment (PhGA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], and US assessments [synovitis or tenosynovitis by grey-scale (GS) and power Doppler (PD) of 42 structures]. An index was created based on statistical models and expert interaction. Construct validity was tested by correlation with DAS28, SDAI, CDAI, and PhGA. Reliability was evaluated in a subgroup of patients with the intraclass correlation coefficient (ICC). US assessment, CRP, and swollen joints were the items that passed the prioritization phase (Delphi study). For the cross-sectional study, 281 patients were randomly divided into design (n = 141) and validation samples (n = 140). The combination of US sites chosen (7 bilaterally) detected the maximum proportion of synovitis and PD present. Three scoring methods were tested: semiquantitative (0-3 GS + 0-3 PD), dichotomous (0/1 GS + 0/1 PD), and qualitative (0/1 based on algorithm). All showed strong correlation with activity measures (? = 0.60), and reliability (ICC 0.89-0.93). The index with best parameters of validity, feasibility, and reliability was the qualitative. The final index chosen was the sum of swollen joint count, US qualitative score, and CRP. The UltraSound Activity score is a valid and reliable measure of inflammation in RA equal to the sum of 28 SJC, a simplified (0/1) US assessment of 11 structures and CRP. It is necessary further investigation to demonstrate additional value over existing indices.

ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDRConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Primary Sjogren syndrome (PSS) is a chronic inflammatory autoimmune disease. Interstitial lung disease (ILD) can be an extraglandular complication. Objective To evaluate the clinical characteristics of patients diagnosed with PSS with ILD. Methods Multicentre cohort study with 25 patients diagnosed with PSS and ILD. Data of PSS, prognostic factors, pulmonary involvement variables, complementary tests that suggest a worse diagnosis and treatment given were collected. EULAR index was measured for Sjogren's syndrome. Results We identified 25 patients. In 15/25 the diagnosis of ILD was done before the diagnosis of PSS. The histopathological patterns found were: 12 NSIP, 5 UIP, 4 OP, 2 LIP. PFRs showed restrictive pattern. The majority of the patients received glucocorticoid therapy, antimalarial or immunosuppressive treatment. Conclusions Patients affected with PSS must be screened to catch a precocious diagnosis of ILD. The majority of the patients were diagnosed of ILD before being diagnosed of PSS. Multicenter cohorts are increasingly demanded and a multidisciplinary management is needed.

Resumen Objetivo Analizar el retraso diagnostico y terapeutico en pacientes con AR de reciente comienzo en 19 centros de Catalunya. Metodos Encuesta epidemiologica en 183 pacientes en que se cuantificaron los tiempos en relacion con el retraso diagnostico midiendo: 1) aparicion del primer sintoma hasta la primera visita a Reumatologia; 2) desde la derivacion hasta la primera visita de Reumatologia; 3) entre aparicion del primer sintoma hasta el diagnostico, y 4) entre aparicion del primer sintoma hasta el inicio del primer FAME. Se definio la existencia de 6 dispositivos asistenciales diferenciados. Resultados El tiempo medio desde el inicio de los sintomas hasta la instauracion de un FAME en pacientes con AR en Catalunya es muy largo (11 meses). Pacientes atendidos en dispositivos como consultas de AR, consultas especializadas en atencion primaria y sobre todo en consultas de artritis de inicio son tratados de manera mas temprana con FAME. Conclusion La existencia de determinados dispositivos asistenciales es fundamental para mejorar la atencion precoz en la AR.

Summary Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. Funding Bill & Melinda Gates Foundation. BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.

Background:Obesity is a predictor for the development of psoriatic arthritis (PsA) with a negative prognostic impact.Objectives:We aimed to describe and characterize patients with PsA according to the Body Mass Index (BMI) in a joint Rheumatology-Dermatology unit (PAIDER).Methods:We retrospectively reviewed patients diagnosed with PsA according to CASPAR criteria visited between May 2012 and May 2019 at the PAIDER clinic of our center. Data on demographic and anthropometric features, serologic findings, source of referral, cardiovascular risk factors and biological treatment were collected from clinical records. Patients were classified according to the WHO International Classification of nutritional status in normal weight (BMI 18.5-24.9 Kg/m2), overweight (BMI 25-29.9 Kg/m2) and obesity (BMI≥30 Kg/m2). A descriptive analysis was performed, and the differences between groups were evaluated using Chi2, T-Student and ANOVA tests. P-values Results:During the study period 393 patients (50.6% women) with a mean age of 52.47 ± 13.21 years were evaluated. Baseline characteristics are shown in table 1.Table 1.Baseline characteristicsTotaln=393Female, n (%)199 (50,6)Age, yrs, mean ±SD52,47 (13,21)Source of referral, n (%) Dermatology117 (29,8) Rheumatology219 (55,7) Primary Care and Others22 (5,6)Smoker, n (%)97 (25,8)High Blood Pressure (HBP), n (%)106 (27,7)Diabetes, n (%)48 (12,5)Hypercholesterolemia, n (%)98 (25,8)Hyperuricemia, n (%)32 (8,6)HLA-B27 positive, n (%)68 (21,6)BMI, Kg/m2, mean ±SD28,15 (5,87)Biological treatment, n (%)166 (43,2)The mean BMI was 28.15 ± 5.87 kg/m2. 112 patients (32%) were overweight with a mean BMI of 27.46 ± 1.55 kg/m2and 118 patients (34%) were obese with a mean BMI of 34.42 ± 5.08 kg/m2. Of the obese patients, 80 (67.8%) had obesity grade 1, 28 (23.7%) grade 2 and 10 (8.5%) grade 3.Characteristics of the patients according to BMI categories are shown in Table 2.Table 2.Characteristics according to BMINormal weightn= 118Overweightn= 112Obesityn=118P valueFemale, n (%)66 (55,9)52 (46,4)62 (52,5)nsAge, yrs, mean ±SD47,92 (14,08)54,71 (11,75)54,48 (11,54)Source of referral, n (%)Ns Dermatology35 (33,7)37 (35,2)34 (30,9) Rheumatology63 (60,6)61 (58,1)70 (63,6) Primary Care and Others6 (5,8)7 (6,7)6 (5,5)Smoker, n (%)37 (33)23 (21,1)31 (26,7)nsHigh Blood Pressure (HBP), n (%)12 (10,5)37 (34,3)41 (35)Diabetes, n (%)7 (6)9 (8,3)30 (25,6)Hypercholesterolemia, n (%)19 (17)24 (22,2)45 (38,5)0,001Hyperuricemia, n (%)5 (4,4)7 (6,8)19 (16,7)0,004HLA-B27, n (%)27 (28,7)17 (17,9)13 (12,6)0,016BMI, Kg/m2, media ±DE22,58 (1,78)27,46 (1,55)34,42 (5,08)-Biological treatment, n (%)47 (41,2)45 (40,9)66 (55,9)0,032We observed that mean age was significantly higher in obese patients (p Conclusion:- Almost 70% of patients with PsA visited in the PAIDER clinic of our center have a BMI above normal and more than a third of them are obese, mostly grade 1.- In our joint clinic there are no differences in BMI regarding the source of referral of the patients.- Patients with obesity are older, have more cardiovascular comorbidities and receive more biological treatment significantly, which increases the complexity of their management and worsens the prognosis.Disclosure of Interests:Andrea García-Guillén: None declared, Ana Laiz: None declared, Anna Lopez-Ferrer: None declared, HyeSang Park: None declared, Patricia Moya: None declared, Berta Magallares: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Ana Milena Millán Arciniegas: None declared, Cesar Díaz-Torné: None declared, Sicylle Jeria: None declared, Hector Corominas: None declared