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Objective SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. Methods We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. Results From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. Conclusion Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

Objective To describe the incidence and fatality of coronavirus disease 2019 (COVID-19) and identify risk factors to fatality in patients with inflammatory articular diseases (IAD). Methods This is a cross-sectional observational study of IAD patients and COVID-19 with controls matched for age, sex, and RT-PCR. A control group was used to compare the cumulative incidence (CI) and case fatality rate (CFR). The main outcomes of the study were CI and CFR. Other variables included comorbidities, treatments, and characteristics of the COVID-19. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with IAD. Results Of the 1537 patients who fulfilled the inclusion criteria, 23/1537 (1.49%) had IAD 13 (0.8%) had rheumatoid arthritis (RA), 5 psoriatic arthritis (PsA) (0.3%) and 5 axial spondyloarthritis (0.3%). There were no significant differences in CI of COVID-19 and CFR in patients with IAD compared with COVID-19 patients without IAD. In RT-PCR positive patients, the CI of COVID-19 in PsA and AS was higher. Of the 23 IAD patients, 2 RA patients (8.6%) died. The patients did no show characteristics of the COVID-19 disease different from the population. In multivariate analysis, the factor associated with fatality in patients with IAD was older age (OR [95% CI], 1.1 [1.0-1.2]). Conclusion COVID-19 CI, fatality rate and other features do not seem to be increased in IAD patients. Older age was associated with fatality in patients with IAD.

Objective: To describe postprandial lipemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis measured as carotid intima-media thickness (cIMT). Methods: We performed an observational study of 40 patients with RA and 40 sex and age-matched controls. Patients with dyslipidemia were excluded. Pathologically increased cIMT was defined as a carotid thickness greater than the 90th percentile (&gt, p90) for age and sex. Fasting and postprandial plasma lipids, cholesterol, triglycerides, apolipoprotein B48 (ApoB48), and total ApoB were evaluated. The other variables included were clinical and laboratory values, Framingham score, and the 28-joint Disease Activity Score (DAS28). Two multivariate models were constructed to identify factors associated with pathologic cIMT in patients with RA. Results: Fasting lipid values were similar in patients with RA and controls, although those of postprandial ApoB48 were higher (median (IQR), 14.4 (10.8&ndash, 12.1) vs. 12.1 (2.3&ndash, 9,8), p = 0.042). Pathologic cIMT was recorded in 10 patients with RA (25%) and nine controls (22.5%). In patients with RA, pathologic cIMT was associated with postprandial ApoB48 (OR (95% CI), 1.15 (1.0&ndash, 1.3)) and total ApoB (OR [95% CI], 1.12 [1.1&ndash, 1.2]). The second model revealed a mean increase of 0.256 mm for cIMT in patients with elevated anticitrullinated protein antibodies (ACPAs). Conclusion: Postprandial ApoB48 levels in patients with RA are higher than in controls. Postprandial ApoB48 and total ApoB levels and markers of severity, such as ACPAs, are associated with pathologic cIMT in patients with RA. Our findings could indicate that these atherogenic particles have a negative effect on the endothelium.

BackgroundThe impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness.MethodsIn this comparative cohort study, we identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression.ResultsThe cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID were increased age (OR 5.31; CI 3.14-8.95), male sex (2.13; CI 1.35-3.36) and having an AI/IMID (OR 1.98; CI 1.15-3.41).ConclusionIn patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19.

Resumen Objetivo Evaluar la efectividad y la seguridad de tocilizumab (TCZ) en pacientes con artritis reumatoide (AR) en practica clinica; la optimizacion de dosis y el cambio de formulacion intravenosa (iv) a subcutanea (sc). Material y metodos Estudio observacional retrospectivo. Se incluyo a 53 pacientes con AR tratados con TCZ. El desenlace principal fue efectividad de TCZ en la semana 24. Variables de desenlace secundarias incluyeron: efectividad en la semana 52, tiempo de retencion del tratamiento, funcion fisica y seguridad. Tambien se midio efectividad de la optimizacion de dosis y del cambio de formulacion iv a sc a los 3 y 6 meses. La efectividad se midio con el indice de actividad segun el Disease activity score-28. Se uso la prueba T pareada o prueba de rangos con signos de Wilcoxon para evaluar efectividad y el tiempo de supervivencia mediante curvas de Kaplan-Meier. Resultados La proporcion de pacientes que alcanzaron la remision o baja actividad de la enfermedad en las semanas 24 y 52 fue del 75,5 y el 87,3%, respectivamente. La media de tiempo de retencion (intervalo de confianza del 95% [IC del 95%]) fue de 81,7 meses (76,6-86,7). Veintiuno de 53 pacientes (39,6%) optimizaron la dosis de TCZ y 35 pacientes cambiaron a TCZ sc desde iv, sin cambios en resultados de efectividad. La tasa de efectos adversos fue 13,6 eventos/100 pacientes-ano. Conclusiones Tocilizumab parece efectivo y seguro en AR en practica clinica. La reduccion de dosis parece efectiva en la mayoria de los pacientes en remision, incluso cuando cambian de iv a sc. Objective To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. Material and methods Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier. Results The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. Conclusions Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC.

Objective To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimised regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. Material and methods Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan–Meier. Results The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6–86.7]). Twenty-one of 53 patients (39.6%) optimised the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. Conclusions Tocilizumab appears to be effective and safe in RA in clinical practice. The optimised regimen appears to be effective in most patients in remission, even when they change from IV to SC.

Objectives: To characterize the gut microbiota profile in rheumatoid arthritis (RA) patients and investigate its association with certain characteristics of RA. Patients and methods: A nested case&ndash, control cohort of 40 patients with RA and 40 sex-age matched controls was studied. Subjects with diabetes, with any other inflammatory disease, practicing extreme diets, taking antibiotics, probiotics or under any new treatment for at least three months prior to sampling were excluded. The microbiota composition was determined by 16S rRNA pyrosequencing and bioinformatics analysis by Quantitative Insights Into Microbial Ecology (QIIME). Other variables included clinical-laboratory variables and average Disease Activity Score 28 points during the follow-up period. Multiple linear regression models were constructed to investigate the possible risk factors for the microbiota. Results: &beta, diversity data showed that patients tend to differ from healthy subjects according to their microbiota (p = 0.07). The analysis showed an increase in Collinsella aerofaciens, Sedimentibacter and Enterococcus genera in patients compared to controls, as well as a decrease in Dorea formicigenerans. Likewise, an increase in the activity of arginine deiminase was observed, which was found in approximately 90% of the RA genes of the genus Collinsela. The sequence number of Collinsella aerofaciens was independently associated with age (B (95%CI), &minus, 0.347 (&minus, 21.6, &minus, 2.1)), high ACPA (0.323 (27.4&ndash, 390.0)) and smoking (0.300 (8.8-256.4)) in RA patients. In addition, we observed decreases in Sarcina, 02d06 and Porphyromonas bacterial lineages. Conclusion: Patients with RA present dysbiosis, resulting from an abundance of certain bacterial lineages and a decrease in others. These alterations could influence the maintenance of autoimmunity to this disease.

Objectives To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD). Patients and methods We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2017. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 24 months. The radiological assessment was centralized. The main outcome measure at 24 months was change in lung function (improvement, stabilization, worsening, or death). We recorded the 28-joint Disease Activity Score 28 (DAS28) and adverse events. A logistic regression analysis was performed to identify factors associated with worsening of ILD. Results After 24 months, lung disease was stabilized in 40 patients (57.1%), improved in 8 (11.4%), and worse in 21 (30.0%). One patient (1.4%) died. The factors associated with worsening of ILD in the multivariate analysis were treatment with abatacept, tocilizumab, or rituximab (OR, 0.102 [95%CI, 0.015-0.686]), DAS28 (OR, 1.969 [95%CI, 1.005-3.857]), and smoking (OR, 6.937 [95%CI, 1.378-4.900]). During follow-up, 30 patients (42.9%) experienced an adverse event, which was severe in 12 cases (17.1%). Conclusions Lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. Non–anti-TNF DMARDs reduce the risk of worsening of lung disease in 90% of patients. The inflammatory activity of RA and smoking, on the other hand, are associated with worsening.

Background/Purpose Ultraviolet radiations act by modifying DNA in sun-exposed skin of lupus patients. We develop a study to analyze the association between climatological conditions and cutaneous manifestations in systemic lupus erythematosus (SLE). Methods Patients data from Spanish Rheumatology Society Lupus Registry (RELESSER) cohort were retrospectively analyzed for presence of cutaneous lesions (alopecia, photosensitivity, malar rash, discoid lesions, oral ulcers and subacute lesions). We included patients who were assessed in rheumatology services from January 2011 to December 2012. Data of climatological conditions throughout the Spanish geography were provided by the Spanish Meteorological Agency. Results A total of 2919 patients were included, 87.3% female. Others biological and clinical data are showed in table 1. In the multivariable model, positive associations were observed between coastal regions OR 1.470 (95% CI:1.080–2.001 p=0,014), anti-DNA OR 1.806 (95% CI:1.276–2.556, p=0.001), antiphospholipids antibodies OR 1.428 (95% CI:1.093–1.864 p=0.009), serositis OR 1.557 (95% CI:1.181–2.053 p=0.002) and arthritis OR 1.804 (95% CI:1.258–2.587 p=0,001). Negative associations were observed between females OR 0.412 (95% CI:0.284–0.599, p=0.000) and antimalarial drugs OR 0.469 (95% CI:0.327–0.671, p=0.000). Conclusion Although the influence of global and ultraviolet radiations on the development of cutaneous lesions in SLE have been suggested, the results of our study does not support an association between the diverse climatological conditions and cutaneous manifestations in SLE. However we observed an independent association with living in coastal areas.

Objectives: To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD). Methods: We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving rituximab between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline, at 12 months, and at the end of follow-up. The main outcome measure at the end of follow-up was forced vital capacity (FVC) > 10% or diffusing capacity of the lungs for carbon monoxide (DLCO) > 15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening ILD. Results: We included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7–69.0) months. At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in seven (18.9%); seven patients (18.9%) died. No significant decline was observed in median FVC (72.2 vs. 70.8; p = 0.530) or DLCO (55.9 vs. 52.2; p = 0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR (95% CI), 0.904 (0.8–0.9); p = 0.015), time to initiation of RTX (1.01 (1.001–1.02); p = 0.029), and mycophenolate (0.202 (0.04–0.8); p = 0.034). Only 28 of the 37 patients (75.6%) were still undergoing treatment with RTX: two patients (5.4%) stopped treatment due to adverse events and seven patients (18.9%) died owing to progression of ILD and superinfection. Conclusion: Lung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD.

Objective: To describe postprandial lipidemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis and inflammatory activity. Methods: Observational study of 80 cases of RA and 80 sex- and age-matched controls. We excluded individuals with dyslipidemia. Postprandial hyperlipidemia (PPHL) was defined as postprandial triglycerides >220 mg/dL and/or postprandial ApoB48 levels >75th percentile (>p75). Plasma lipids, cholesterol, triglycerides, ApoB48, and total ApoB were evaluated at baseline and after a meal. Other variables analyzed included subclinical atherosclerosis (defined as presence of carotid atheromatous plaque), inflammatory activity (disease activity score (DAS28-ESR)), cytokines, apolipoproteins, and physical activity. A multivariate analysis was performed to identify factors associated with PPHL in patients with RA. Results: A total of 75 patients with RA and 67 healthy controls fulfilled the inclusion criteria. PPHL was more frequent in patients with RA than controls (No. (%), 29 (38.70) vs. 15 (22.40); p = 0.036), as was subclinical atherosclerosis (No. (%), 22 (30.10) vs. 10 (14.90); p = 0.032). PPHL in patients with RA was associated with subclinical atherosclerosis (OR (95% CI) 4.69 (1.09–12.11); p = 0.037), TNF-α (OR (95% CI) 2.00 (1.00–3.98); p = 0.048), high-sensitivity C-reactive protein (OR (95% CI) 1.10 (1.01–1.19); p = 0.027), and baseline triglycerides (OR (95% CI) 1.02 (1.00–1.04); p = 0.049). Conclusion: PPHL was more frequent in patients with RA than in controls. PPHL in patients with RA was associated with inflammation and subclinical atherosclerosis.

Background:TNF inhibitors (TNFi) represent an extraordinary advance in the management of Rheumatoid Arthritis (RA). Despite their benefits, there is a percentage of patients (20–40%) that do not achieve clinical improvement. Therefore, it is necessary to search for new and easily accessible biomarkers predictive of therapeutic response that might guide precision medicine.Objectives:1. To explore changes in the molecular profile of RA patients following TNFi therapy in serum samples. 2. To search for new and reliable biomarkers predictive of TNFi response, based on clinical and molecular profiles of RA patients, by using machine learning algorithms.Methods:In a prospective multicenter study, 79 RA patients undergoing TNFi and 29 healthy donors (HD) were enrolled. Twenty-two RA patients were further included as a validation cohort. Serum samples were obtained before and after 6 months of treatment, and therapeutic efficacy was evaluated. Patients’ response was determined following EULAR response criteria. Serum inflammatory profile was analyzed by a multiplex immunoassay, along with oxidative and NETotic profiles, evaluated by commercial kits. A circulating miRNA array was also performed by next-generation sequencing. Clustering analysis was carried out to identify groups of patients with distinctive molecular signatures. Then, clinical and molecular changes induced by TNFi were delineated after 6 months of therapy. Finally, integrative clinical and molecular signatures as predictors of response were assessed at baseline by supervised machine learning methods, using regularized logistic regressions.Results:Inflammatory, oxidative stress and NETosis-derived biomolecules were found altered in RA patients versus HD, closely interconnected and associated with several deregulated miRNAs. This altered molecular profile at baseline allowed the unsupervised division of three clusters of RA patients with distinctive clinical phenotypes, further linked to TNFi effectiveness. Cluster 1 included RA patients with low levels of pro-inflammatory cytokines, associated with a medium-low disease activity score and good clinical response. Clusters 2-3 comprised patients with high levels of pro-inflammatory cytokines, associated with a high disease activity and a non-response rate of 30%.After 6 months of therapy the molecular profile found altered in RA patients was reversed in responder patients, who achieved a molecular phenotype similar to HDs. However, non-responder patients’ molecular profile remained significantly deregulated, including alterations in inflammatory mediators (IL-6, L-8, TNFα, VEGF, IL-1RA, IL-5, IL-15, GMCSF, GCSF, FGFb), oxidative stress markers (LPO) and NETosis-derived products (Elastase), along with specific miRNAs (miR-199a-5p). These molecular changes further correlated with changes in disease activity score. Machine-learning algorithms identified clinical (Creatinine, IgM, Vitamin D, Swollen Joints, C4, Disease Duration and Tryglicerides) and molecular (Nucleosomes, IL-10, miR-106a-5p, IL-13, IL-12p70, IL-15 and LPO) signatures as potential predictors of response to TNFi treatment with high accuracy. Furthermore, the integration of both features in a combined model increased the predictive value of these signatures (AUC: 0.91). These results were further confirmed in an independent validation cohort.Conclusion:1. RA patients display distinctive altered molecular profiles directly linked to their clinical status and associated with TNFi effectiveness. 2. Clinical response was associated with a specific modulation of the inflammatory profile, the reestablishment of the altered oxidative status, the reduction of NETosis and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.Disclosure of Interests:None declared

Background:Factors associated with the development of chronic heart failure (CHF) in systemic lupus erythematosus (SLE) have received little attention. On the other hand, recent data from the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection during the COVID19 pandemic have cast some doubts on its cardiological safety.Objectives:To identify factors associated to CHF in SLE.Methods:Retrospective cross-sectional study, including all patients with SLE (≥4 ACR-1997 criteria) recruited in RELESSER registry. The objectives and methodology of the registry have been described previously (1). CHF was defined according to the Charlson index item. Patients with CHF before diagnosis of SLE were excluded. Cumulative damage was measured with the SLICC/ACR index, excluding cardiovascular (CV) items (mSDI). Multivariate analysis exploring factors associated with CHF was carried out.Results:117 patients (3% of the entire cohort) with SLE and CHF and 3,506 controls with SLE without CHF were included. 90% were women. Disease duration: mean (SD), 120.2 (87.7) months. CHF appeared after a median (P25-P75) of 9.40 (4.2-18.3) years from SLE diagnosis. Patients with CHF were older (59.8 ± 18.2 vs. 46.2 ± 4.3). In the bivariate analysis, the association of CHF with greater severity [Katz severity index: median (IQR): 4 (3-5) vs. 2 (1-3)], damage [mSDI: 3 (2-4) vs 0 (0-1)], comorbidity [modified Charlson- excluding CV items: 4 (3-6) vs 1(1-3)] and both CV (37.5% vs 6.7%) and overall mortality (43.2% vs 4.7%) (pTable 1.Congestive heart failure associated factors (multivariable analysis)Odds Ratio95% CIP-valueSex (female)0.460.25 - 0.880.0147Ischaemic cardiopathy7.964.01 - 15.48Cardiac arrhythmia7.384.00 - 13.42Pulmonary hypertension3.711.84 - 7.250.0002Cardiac valvulopathy6.333.41 - 11.62Hospitalization (due to SLE)3.741.81 - 8.650.0008Calcium or vitamin D5.292.07 - 16.860.0015Antimalarials0.280.17 - 0.45mSDI *1.291.16 - 1.44*mSDI = modified SLICC/ACR damage index (without cardiovascular items)Conclusion:- CHF is a rather late complication of SLE.- Patients with SLE and CHF have more severe SLE, with greater refractoriness to SLE treatments and higher overall mortality.- Treatment with antimalarials, as routinely used in SLE patients, is not only safe to heart, but even appears to have a cardioprotective effect.References:[1]Rúa-Figueroa I, López-Longo FJ, Calvo-Alén J, et al. National registry of patients with systemic lupus erythematosus of the Spanish Society of Rheumatology: objectives and methodology. Reumatol Clin. 2014;10(1):17-24.Acknowledgements:Research Unit of Spanish Society of RheumatologyDisclosure of Interests:None declared

The aims of this study were to evaluate adherence of rheumatoid arthritis (RA) patients to biological disease-modifying antirheumatic drugs (bDMARDs), identify potential risk factors, and analyze the discriminative ability of the Morisky–Green test (MGT) to detect bDMARD nonadherence. One hundred and seventy-eight adult RA patients treated with bDMARDs were included. Adherence was measured using the medication possession ratio (MPR) of the previous 6 months. An MPR >80% was considered good adherence. Patient demographics, clinical characteristics, and MGT scores were assessed through a standardized clinical interview at the cross-sectional date. One-hundred and twelve patients (63%) were taking subcutaneous bDMARDs, while 66 (37%) were taking intravenous drugs. One-hundred fifty-eight (88.8%) showed good adherence to bDMARDs, while 79 (61.2%) also correctly took concomitant conventional synthetic DMARDs (csDMARDs). In logistic regression models, nonadherence to bDMARDs was associated with higher disease activity [odds ratio (OR) 1.45; 95% CI, 1.03–2.03; p = 0.032] and subcutaneous route (OR 3.70; 95% CI 1.02–13.48; p = 0.040). MGT accurately identified an MPR >80% of bDMARDs in 76.9% of the patients. A sensitivity of 78%, specificity of 70%, positive predictive value of 95.3%, negative predictive value of 28.5%, positive likelihood ratio (LR) of 2.6, and negative LR of 0.3% were obtained. Adherence may be good for bDMARDs but is low for csDMARDs. Low adherence for bDMARDs is associated with poorer disease control during the past 6 months and use of subcutaneous route. These findings should alert doctors to consider possible low adherence before declaring treatment failure.

To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants’ clinical experience when only low quality evidence was available. A total of 18 recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.

To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants' clinical experience when only low quality evidence was available. A total of eighteen recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.

Objective: To describe the incidence of bacteremia in a large multicentric cohort of patients with systemic lupus erythematosus (SLE) and their clinical characteristics and to identify risk factors. Methods: All bacteremic episodes from the Spanish RELESSER registry were included. Clinical and laboratory characteristics concerning bacteremia and SLE status, as well as comorbidities at the time of infection, were retrospectively collected. A comparison with sex- and age-matched SLE controls without bacteremia was made. A logistic regression was conducted. Results: The study included 114 episodes of bacteremia in 83 patients. The incidence rate was 2.7/1000 patient-years. At the time of bacteremia, the median age was 40.5 (range: 8-90) years, and 88.6% of patients were female. The Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index was 4 [interquartile range (IQR) 8]; 41% had an SLE flare (66% severe); Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was 3 (IQR 4). A comorbidity was recorded in 64% of cases. At the time of bacteremia, 88.6% received corticosteroids (68.6% > 10 mg/day) and 57% immunosuppressors. Gram-negative bacilli, most frequently Escherichia coli (29.8%), caused 52.6% of the episodes. The bacteremia-related mortality was 14% and bacteremia was recurrent in 27.2% of cases. A dose-response relationship was found between corticosteroids and bacteremia risk. In the multivariate analysis, these factors were associated with bacteremia: elevated creatinine (OR 1.31, 95% CI 1.01-1.70; p = 0.045), diabetes (OR 6.01, 95% CI 2.26-15.95; p < 0.001), cancer (OR 5.32, 95% CI 2.23-12.70; p < 0.001), immunosuppressors (OR 6.35, 95% CI 3.42-11.77; p < 0.001), and damage (OR 1.65, 95% CI 1.31-2.09; p < 0.001). Conclusion: Bacteremia occurred mostly in patients with active SLE and was frequently associated with severe flares and corticosteroid use. Recurrence and mortality were high. Immunosuppressors, comorbidities, and disease-related damage were associated with bacteremia. This work was supported by the Spanish Foundation of Rheumatology. JMPR is supported by grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/ REGPOT-2012-2013.1) and FIS/ISCIII-Fondo Europeo de Desarrollo regional (FEDER) (Grant number PI11/02857).

Background: The impact of chronic inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. Methods: In this comparative cohort study, we systematically identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. Findings: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Patients were on treatment with glucocorticoids (40%), conventional synthetic disease modifying antirheumatic drugs (csDMARD) (57%), targeted synthetic or biological (ts/bDMARD) (23%), or other immunosuppressants (12%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31·6% in the rheumatic and 28·1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe were increased age (OR 5·31; CI 3·14-8·95), male sex (2·13; CI 1·35-3·36) and having an AI/IMID (OR 1·98; CI 1·15-3·41). Interpretation: In patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19. Funding Statement: The RIER network was supported by Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (RD16/0012 RETICS program) and cofinanced by the European Regional Development Fund. Declaration of Interests: None of the authors have competing interests to declare. Ethics Approval Statement: The study was approved by Comite de Etica de la Investigacion del Hospital Universitario 12 de Octubre, CEIm number: 20/160.

Introduction Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Materials and methods Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry. Results We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE ( p Conclusions SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.

Background Little is known about the patient related outcomes and disease activity in systemic lupus erythematosus. Damage and impact are issues that have not been associated with activity in lupus previously. Objectives In a large cohort of systemic lupus erythematosus (SLE) patients, to evaluate the association between a Patient Acceptable Symptom State (PASS) and three different domains of the disease: activity, damage and impact of SLE on patients’ lives Methods Cross-sectional study of 1,364 SLE (ACR 97 Criteria) patients from the Spanish Society of Rheumatology Lupus Registry (RELESSER). Patients were clinically assessed by the physicians, who collected data about demographics, clinical manifestations, laboratory features and therapies. SLE activity was assessed by using the SLEDAI (SLE Disease Activity Index). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) was used to measure damage accrual. The impact of SLE on patients’ lives was evaluated by using the Lupus Impact Tracker (LIT). The PASS question “Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory?” was answered in a dichotomized way: yes/no. Measures of central tendency and spread were used to describe responses and T-test was used to evaluate the independence between PASS and the other questionnaires and indices. Results Mean age (years) ± S.D. of the 1,364 patients included in the study was 49.9 ± 13.3; 90.3% were female and 94.9% were Caucasian. In the total of patients, 979 (71.8%) were in PASS. Patients in PASS had significantly lower activity (SLEDAI Score) than those not in PASS (2.4 ± 3.2 vs. 3.0 ± 3.9, respectively; p=0.007). The SLICC/ACR DI was significantly lower in the group of patients in PASS compared to those without PASS (0.64 ± 1.1 vs. 0.81 ± 0.21, respectively; p=0.022). SLE had a significantly lower impact on patients in PASS in comparison to those without PASS (LIT Score: 8.47 ± 7.5 vs. 19.8 ± 8.34, respectively; p=0.001). Conclusion In the largest observational European Registry of SLE patients, PASS was associated with other domains of the disease: activity, damage and impact on patients’ life. PASS is a simple and reliable patient-reported outcome that can be a useful tool to evaluate patients’ well-being. Disclosure of Interests Tomas Vazquez Rodriguez: None declared, Inigo Rua Figueroa: None declared, Victor Del Campo Perez: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Francisco J Lopez-Longo: None declared, Maria Galindo-Izquierdo: None declared, Jaime Calvo-Alen: None declared, Antonio Fernandez-Nebro: None declared, Juan Ovalles: None declared, Pilar Rubio Munoz: None declared, Eva Tomero Muriel: None declared, Coral Mourino Rodriguez: None declared, Esther Uriarte Isacelaya: None declared, Angela Pecondon-Espanol: None declared, Mercedes Freire Gonzalez: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Marian Gantes Mora: None declared, Monica Ibanez Barcelo: None declared, Carlos A. Montilla-Morales: None declared, Jose M Pego-Reigosa: None declared

Objectives To asses insulin resistance (IR) in patients with rheumatoid arthritis (RA) and compare it with healthy controls and to analyze the association between the accumulated inflammatory burden in patients with RA and IR. Methods Design: Nested case-control study. Population: consecutive RA-patients (ACR/EULAR 2010 criteria), >16 years, selected from a prospective inception cohort (diagnosis of RA between 2007 and 2011). Patients with Diabetes Mellitus (according to ADA 2010 criteria) were excluded. Controls: sex- age and BMI -matched controls were collected from a health center in our hospital area. Protocol: Cases and controls were evaluated by a rheumatologist. Clinical data of disease activity (RA patients), analytical values and oral glucose tolerance test (OGTT) were determined. Main outcome: IR measured by the homeostasis model for insulin resistance (HOMA-IR) (IR> 2.29 μU*mmol/ml). Secondary outcome: IR measured by quantitative insulin sensitivity check index (QUICKI) ( Results Two hundred subjects were studied, 31 of them were excluded after OGTT. Finally 169 subjects were included; 89 RA and 80 controls. The mean age of patients with RA was 56.6(±10.9) years. Most of them were women (75.3%), with seropositive (FR 82.0% y ACPA 75.3%) and erosive (61.1%) RA. The average duration of the disease was 98 months (8.1 years). The delay in the diagnosis of RA was 10.9 months (5.4 - 25.6) with a mean DAS28 index since the beginning of the disease of 3.11 (0.8). Differences between clinical characteristics and in relation to IR between cases and controls are shown in Table 1. No significant differences in the proportion of subject with IR in cases and controls were observed and 28.1% of patients with RA had IR. Of the 25 patients with IR, the majority, 68%, presented a DAS28 score> 3.2 (moderate-high activity index). In multivariate analysis, the independent variables associated with IR in patients with RA were: Obesity [OR=6.01; β=1.795 (p=0.002), disease activity (OR=2.77; β=1.021 [p=0.009]]) Il-1β (OR=1.59; β=0.464 (p=0.024)). This model would explain 37.5% of the variability of the IR (R2=0.375). Conclusion We did not find an increased IR in patients with RA compared with healthy controls, which may be due to adequate treatment and good control of inflammatory activity in the most of patients with RA. Obesity, inflammatory activity (measured by mean DAS28 index) and IL-1 β were the predictors of IR in patients with RA in our study. References [1] Insulin resistance and levels of adipokines in patients with untreated early rheumatoid arthritis. Manrique-Arija S, et al. Clin Rheumatol. 2016;35(1):43-53. [2] Abnormal Glucose Metabolism in Rheumatoid Arthritis. Pi H1, Zhou H1, Jin H1, et al. Biomed Res Int. 2017;2017:9670434. [3] Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients. Castillo-Hernandez J. Rev Bras Reumatol Engl Ed. 2017;57(4):320-329. Acknowledgement I thank the Rheumatology Spanish Society for Grant support in 2015 -2017 for this work. Disclosure of Interests Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Natalia Mena-Vazquez: None declared, Inmaculada Urena : None declared, F. Gabriel Jimenez-Nunez: None declared, Clara Fuego-Varela: None declared, Antonio Fernandez-Nebro: None declared

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in SLE patients. Objectives Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome. Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results We included 3651 SLE patients and 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin antibodies, 27.3% showed positivity for anti b2glycoprotein I and 24% for lupus anticoagulant). Overall 2283 patients were classified as SLE no aPL, 528 as SLE-APS and 840 as SLE-aPL. Demographic data, clinical and laboratory features in the different groups are showed in Table 1. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than SLE-aPL and SLE no aPL patients (p 0.5 grs), urinary cell casts, seizures and psychosis (p≤0.001). Overall, SLE-APS patients showed a lower rate of cutaneous manifestations and higher rates of neuropsychiatric, cardiac, pulmonary, renal, joint and ophthalmological manifestations (Table 1). In accordance with a more severe clinical profile, higher frequency of anti-DNA antibodies and hypocomplementemia were observed in the SLE-APS group (p Conclusion SLE-APS patients show a more severe clinical profile with higher frequency of major organ involvement and more damage accrual than SLE-aPL and SLE no APL. Disclosure of Interests Leyre Riancho-Zarrabeitia Grant/research support from: Abbvie, Pfizer, UCB, MSD, GSK, Amgen, Roche travel grants, Victor Martinez Taboada: None declared, Inigo Rua-Figueroa: None declared, Fernando Sanchez-Alonso: None declared, Maria Galindo-Izquierdo: None declared, Juan Ovalles: None declared, Alejandro Olive Grant/research support from: ND, Consultant for: ND, Paid instructor for: ND, Speakers bureau: ND, Antonio Fernandez-Nebro: None declared, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb, Raul Menor Almagro: None declared, Eva Tomero Muriel: None declared, Esther Uriarte Isacelaya: None declared, Alina Boteanu: None declared, Mariano Andres: None declared, Mercedes Freire Gonzalez: None declared, Gregorio Santos Soler: None declared, Esther Ruiz Lucea: None declared, Monica Ibanez Barcelo: 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, Carles Galisteo: None declared, Victor Quevedo Vila: None declared, Enrique Raya: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Lorena Exposito: None declared, Jose A Hernandez Beriain: None declared, Loreto Horcada: None declared, Jose M Pego-Reigosa: None declared

Background Immune-Mediated Inflammatory Diseases (IMIDs) are a group of conditions/diseases characterized by common pathways leading to inflammation, which may result from a dysregulation of the normal immune response. The activity of these diseases is usually measured by the assessment of clinical symptoms. Objectives To apply a three-stage proteomic strategy to find plasma biomarkers useful to monitor disease activity in patients three different IMIDs: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE). Methods A three-stage proteomic strategy was conducted: 1) Discovery stage: a random selection of 80 plasma samples from patients with different RA activities according to the DAS28, which were classified as low activity (LA, n=40) and high activity (HA, n=40). The analysis was conducted by shotgun mass spectrometry (MS) applying an iTRAQ 8-plex strategy, by nanoLC-MS/MS using three different MS instruments. 2) Verification stage: a targeted proteomics strategy was used to verify the candidate biomarkers from the screening, using the same 80 samples of this first stage. This analysis was performed by Multiple Reaction Monitoring (MRM) with the aid of synthetic heavy-labelled peptides, by nanoLC-MS/MS in an ESI-QTRAP 5500. 3) Validation stage: ELISA experiments were performed to confirm the previous results on an independent set of plasma samples from patients with RA (n=170), PsA (n=80) and SLE (n=80). Results 1) Discovery stage: The MS analysis led to the identification of 186 proteins. A panel of 9 proteins was identified as candidate biomarkers for disease activity monitoring in RA. Most of these proteins are related with the pathogenic process and the effects caused by this type of disease (inflammation and immune disorder in joints). 2) Verification stage: four from the 9 proteins (SAA1, AACT, HPT, A1AG1) were found to be quantitatively altered between patients with extreme disease activities (p Conclusion Using a three-stage proteomic strategy, we have identified HPT, SAA1 and AACT as protein biomarker candidates for monitoring PsA activity. Disclosure of Interests Lucia Gonzalez Rodriguez: None declared, Valentina Calamia: None declared, Rocio Paz Gonzalez: None declared, Patricia Fernandez Puente: None declared, Cristina Ruiz-Romero: None declared, Juan D. Canete: None declared, Antonio Julia: None declared, Antonio Fernandez Nebro: None declared, Jesus Tornero: None declared, Sara Marsal: None declared, Francisco J. Blanco Consultant for: AbbVie, Bioiberica, BMS, GSK, Grunenthal, Janssen, Lilly, Pfizer, Regeneron, Roche, Sanofi, TRB Chemedica, and UCB

Objectives: Describe the intestinal microbiome profile in RA patients and analyze the mechanisms through which intervenes in the pathogenesis RA. Methods: Design: Controlled, observational, cross-sectional study of established RA cohort. Patients: Forty consecutive RA patients (ACR/EULAR 2010 criteria) >16 years, selected from a prospective inception cohort (2007-2011) and 40 sex-age matched healthy controls. Protocol: Cases and controls were evaluated by a rheumatologist. Clinical data of disease activity were collected during the follow-up and analytical values were determined. Fecal samples were frozen within 24 hours of collection. Main outcome: Fecal samples exam. Microbial DNA was extracted from fecal samples using QIAamp DNA stool Mini kit. The concentration and quality of DNA was determined by Nanodrop. Secondary Other variables: Demographic, clinical-analytical and therapies (DMARDs). Statistical analysis: Analysis of microbiota prole: UniFracPCoA (Principal Coordinate Analysis) was performed with the abundance data of operational taxonomic units (OTU) by means of the variancecovariance matrix implemented in Quantitative Insights Into Microbial Ecology(QIIME). The relative abundance of each OTU (taxa) was compared using a Wilcoxon test. The variations of abundance and diversity were compared by ANOSIM pathway. The calculation of α and β-diversity was carried out using QIIME. Results: Most of subjects were women (75%) (table). In RA patients, the average DAS28 was 3.6. β-diversity data showed that patients tend to dier from healthy subjects according to their microbiota (p = 0.07). Patients with RA exhibited decreased gut microbiome diversity compared with controls, although was not statistically signicant. Regarding in species richness, the analysis suggested an increase of the Collinsella aerofaciens species and enterococcus genera in patients compared with controls. Likewise, an increase of arginine deaminase activity was observed, which belonged, in approximately 90%, to the RA genes of the genus Collinsela.The multivariate analysis identified ACPA positive (s [95% CI], 0.33 [27.4-390]), smoking (0.3 [8.8-256.4]) and age (-0.3 [27.4-390.0]) as factors associated with Collinsela.Also, we observed a decrease in other bacterial lineages. On the other hand, RA patients showed an altered metabolic capacity for the transport of zinc and copper. Conclusion: These observations suggest a dysbiosis in RA patients, resulting from the abundance of certain bacterial (i.e Collinsela) and decrease of other bacterial lineages. These alterations could inuence in a signicant way in the perpetuation of the autoimmunity of the disease. Disclosure of Interests: Natalia Mena-Vazquez: None declared, Patricia Ruiz-Limon: None declared, Isabel Moreno-Indias: None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Francisco Jose Tinahones: None declared, Antonio Fernandez-Nebro: None declared

Objectives: To study the prevalence of anxiety and depression in a cohort of patients with SLE at King’s College Hospital in London,as well as its relationship with characteristics of disease and treatments Methods: Cross-sectional study of a cohort of patients with SLE.All patients with SLE who had been included in the IMPARTs project(Integrating Mental and Physical healthcare:Research,Training and Services)were recruited between 2012-2016.All patients filled out the following questionnaires on a tablet device:PHQ9(Patient Health Questionnaire)(Scores of 10 or more have an sensitivity and specifity close to 90% for major depression) and GAD-7(7-item Generalized Anxiety Disorder)(Scores of 10 or more have an sensitivity and specifity close to 89% and 82% for GAD).Variables:demographic, duration of the disease(months)and the profile of autoantibodies.Previous history of depression or anxiety. SLEDAI,treatments,ESR, CPR,C3 and C4.Statistical analysis:descriptive, bivariate using T-Student and χ2. Results: A total of 129 patients with SLE were included. Clinical characteristics in Table 1. 38 patients (29.5%)had some degree of major depression and 27(20.9%)generalized anxiety disorder(Table 2).The prevalence of major depression was higher in patients with anti RO52(42.3%vs23.8%, p=0.06),with generalized anxiety (81.5%vs 15.7%,p Conclusion: The prevalence of anxiety and depression in our group of patients was high,both related, as well as with the perception of pain and fatigue.A correct assessment of these manifestations and early treatment could help improve the quality of life of patients Disclosure of Interests: None declared

Background Objectives Estimate the frequency of the association of SLE with other autoimmune diseases in a large Spanish cohort of patients with systemic lupus erythematosus (SLE). Methods Design RELESSER is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. Patients: Unselected consecutive adult patients with SLE, classified according to the ACR 1997 criteria. Main outcome: Polyautoimmunity was defined as patients who fulfilled criteria for SLE and other autoimmune disease: autoimmune thyroiditis, rheumatoid arthritis, systemic sclerosis or inflammatory myopathy and mixed connective tissue disease. Multiple autoimmune syndrome (MAS) was defined as patients who meet SLE criteria and at least two other autoimmune diseases. Statistical analysis: Descriptive. Multiple logistic regression analysis to investigate the possible risk factors for polyautoimmunity in patients with SLE. Results From 3679 (91.4%) patients included in the registry, 501 (13.6%) had Polyautoimmunity. The characteristics are showed in Table. The most frequent polyautoimmunity types associated with SLE were: autoimmune thyroiditis (7.5%), other connective tissue disorders (7.1%). Other autoimmune diseases not considered within the scope of Polyautoimmunity was 12.8% for Sjogren’s syndrome and 12.7% for antiphospholipid syndrome. A family history of SLE was 12.4% and MAS in 10.2%. The multivariate analysis identified age (odds ratio [95% CI], 1.01 [1.00-1.02]), sex (3.00 [1.48-6.04]), Raynaud’s phenomenon (1.79 [1.34-2.39]), pulmonary fibrosis (2.88 [1.32-6.30]), Ro-La autoantibodies (1.68 [1.20-2.36]), antiRNP (1.79 [1.32-2.42]) and treatment with methotrexate (1.54 [1.08-2.18]) or with antimalarials (0.57 [0.41-0.78]) as factors associated with polyautoimmunity. Conclusion SLE patients associated poliautoimmunity in 14%, MAS in 2%. More studies are needed to better understand the increase of polyautoimmunity in these patients. Disclosure of Interests Natalia Mena-Vazquez: None declared, Antonio Fernandez-Nebro: None declared, Inigo Rua-Figueroa: None declared, Maria Galindo-Izquierdo: None declared, Juan Ovalles: None declared, Alejandro Olive Grant/research support from: ND, Consultant for: ND, Paid instructor for: ND, Speakers bureau: ND, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb, Raul Menor-Almagro: None declared, Eva Tomero Muriel: None declared, Esther Uriarte Isacelaya: None declared, Alina Boteanu: None declared, Mariano Andres: None declared, Mercedes Freire Gonzalez: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Tomas Vazquez Rodriguez: None declared, Ricardo Blanco: None declared, Jose A Hernandez Beriain: None declared, Jesus Ibanez: None declared, Enrique Raya: None declared, Joan Calvet: None declared, Jose M Pego-Reigosa: None declared

Objectives: To estimate the incidence of cancer in systemic lupus erythematosus (SLE) patients and to analyze factors associated with cancer differentiating between hormone-sensitive (HS) and non-HS cancers. Methods: Multicenter retrospective study of a cohort of patients included in Spanish Society of Rheumatology Lupus Registry (RELESSER). The first cancer after the diagnosis of SLE, sociodemographic, clinical, activity, cumulative damage, severity, comorbidity, treatments, and refractory disease data were collected. Cancers were classified into HS (prostate, breast, endometrial and ovarian) and non-HS (the rest). Standardized incidence ratio (SIR) was calculated and logistics regression models were constructed to identify factors associated with cancer. Results: We included 3539 patients (90.4% women) with SLE (ACR-97 criteria), of whom 154 had cancer (91% women), and 44 were HS (100% women). The SIR for cancer was 1.37 (95% CI: 1.15-1.59), reaching higher values in women under 65 years [2.38 (95% CI: 1.84-2.91)]. The SIR in women with cancer HS vs. non-HS was 1.02 (95% CI: 0.13-1.91) and 1.93 (95% CI: 0.98-2.89)], respectively. In HS vs. non-HS cancers, age at diagnosis of SLE [Odds ratio (OR) 1.04 (p = 0.002) vs. 1.04 (p = 0.019), respectively] and the evolution time [OR 1.01 (p Conclusion: The incidence of cancer in patients with SLE is increased compared to the Spanish population, specially in younger women. This increase might be due to non-HS cancers. SLE with more cumulative damage and more prescription of ACE inhibitors might associate with non-HS cancers. Disclosure of Interests: Tatiana Cobo-Ibanez: None declared, ANA URRUTICOECHEA-ARANA: None declared, Inigo Rua-Figueroa: None declared, Maria Auxiliadora Martin-Martinez: None declared, Juan Ovalles: None declared, Maria Galindo-Izquierdo: None declared, Jaime Calvo-Alen: None declared, Alejandro Olive: None declared, Antonio Fernandez-Nebro: None declared, Raul Menor-Almagro: None declared, Eva Tomero Muriel: None declared, Loreto Horcada: None declared, Esther Uriarte Isacelaya: None declared, Victor Martinez Taboada: None declared, Jose Luis Andreu: None declared, Alina Boteanu: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Cristina Bohorquez: None declared, Carlos A. Montilla-Morales: None declared, Gregorio Santos Soler: None declared, Blanca Hernandez-Cruz: 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, Eva Salgado Perez: None declared, Mercedes Freire Gonzalez: None declared, Jose A Hernandez Beriain: None declared, Elvira Diez Alvarez: None declared, Lorena Exposito: None declared, Olaia Fernandez- Berrizbeitia: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen, Jose M Pego-Reigosa: 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

Objectives. This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. Methods. RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. Results. Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. Conclusion. Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies., The RELESSER Registry was partially funded by GlaxoSmithKline (GSK), Roche, Union Chimique Belge (UCB), Lilly and Novartis. The sponsors had no role in the study design, data collection, analysis or interpretation, in writing the report, or in the decision to submit the article for publication. J.M.P.-R. is supported by grant 316265 (BIOCAPS) from the European Union 7th Framework Program (FP7/REGPOT-2012-2013.1). The study was supported by FIS Grant PI11/02857 (Instituto Carlos III, Fondos FEDER). Grant for medical researchers of the 'Fundacion Espanola de Reumatologia'.

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in SLE patients. Objectives To investigate the association between the different aPL and SLE manifestations as well as to elucidate the influence of the load of antibodies. Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results Out of a total of 3651 SLE patients, 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin (aCL) antibodies, 27.3% for anti b2glycoprotein I (aB2GPI) and 24% for lupus anticoagulant (LA)). Regarding the load of antibodies, 20.6%, 12.1% and 4.8% were positive for one, two and three antibodies, respectively. The association between the different aPL, the number of positive antibodies and antiphospholipid syndrome related manifestations is showed in Table 1. Overall, all types of aPL were associated with classic APS manifestations, although LA, IgG isotypes, and patients with more than one aPL display a higher risk to develop clinical APS. Regarding specific lupus manifestations, all aPL types showed a significant negative association with cutaneous manifestations. LA and aCL were associated with an increased risk of cardiac, respiratory and neuropsychiatric manifestations (p Conclusion There is a hierarchy for aPL and the risk of APS and lupus manifestations. aCL, and especially LA, confer a higher risk for major organ involvement in SLE patients. IgG isotypes and the load of aPL antibodies increase the risk for clinical APS and major lupus manifestations. Disclosure of Interests: Leyre Riancho-Zarrabeitia Grant/research support from: Abbvie, Pfizer, UCB, MSD, GSK, Amgen, Roche travel grants, Victor Martinez Taboada: None declared, Inigo Rua-Figueroa: None declared, Fernando Sanchez-Alonso: None declared, Maria Galindo-Izquierdo: None declared, Juan Ovalles: None declared, Alejandro Olive Grant/research support from: ND, Consultant for: ND, Paid instructor for: ND, Speakers bureau: ND, Antonio Fernandez-Nebro: None declared, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb, Raul Menor-Almagro: None declared, Eva Tomero Muriel: None declared, Esther Uriarte Isacelaya: None declared, Alina Boteanu: None declared, Mariano Andres: None declared, Mercedes Freire Gonzalez: None declared, Gregorio Santos Soler: None declared, Esther Ruiz Lucea: None declared, Monica Ibanez Barcelo: 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, Carles Galisteo: None declared, Victor Quevedo Vila: None declared, Enrique Raya: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Lorena Exposito: None declared, Jose A Hernandez Beriain: None declared, Loreto Horcada: None declared, Jose M Pego-Reigosa: None declared

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus (SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results We included 3651 SLE patients and 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin antibodies, 27.3% showed positivity for anti b2glycoprotein I and 24% for lupus anticoagulant). Overall 2283 patients were classified as SLE no aPL, 528 as SLE-APS and 840 as SLE-aPL. Demographic data, clinical and laboratory features in the different groups are showed in table 1. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than SLE-aPL and SLE no aPL patients (p 0.5 grs), urinary cell casts, seizures and psychosis (p0.001). Overall, SLE-APS patients showed a lower rate of cutaneous manifestations and higher rates of neuropsychiatric, cardiac, pulmonary, renal, joint and ophthalmological manifestations (table 1). In accordance with a more severe clinical profile, higher frequency of anti-DNA antibodies and hypocomplementemia were observed in the SLE-APS group (p Conclusions SLE-APS patients show a more severe clinical profile with higher frequency of major organ involvement and more damage accrual than SLE-aPL and SLE no APL. Funding Source(s): None

Background Remission and Low Disease activity state (LDAS) are physician assessed treat to target-T2T outcomes for Systemic Lupus Erythematosus (SLE). Lupus Impact Tracker (LIT), a ten-item unidimensional patient reported tool has good psychometric properties and responds to patient reported changes in health, physician based disease activity (DA) and composite response Index (SRI). Herein we report responsiveness of LIT to changes in physician (T2T) and patient assessed outcomes (DA by SLAQ and health status (EQ5D)) among SLE patients from the largest European SLE registry- cohort. Methods One-year longitudinal, observational, multi-center data from 1364 adult patients with SLE meeting 1997 ACR criteria were obtained from baseline and year 1 visit. This included demographics, patient reported tools (LIT, EQ5D VAS, SLAQ), SLE (activity-SLEDAI) and medications. Remission off therapy (ROFT) was defined as SLEDAI=0 without prednisone or Immunosuppressive/s. Remission on-therapy (RONT) was SLEDAI=0 and a prednisone dose 5 mg/day and/or Immunosuppressive/s (maintenance dose). LDAS (modified) was defined as SLEDAI 4, prednisone dose 9 mg/day and/or maintenance immunosuppressive/s. Non-optimal (NO) disease status was SLEDAI >4 and/or prednisone dose >9 mg/day and/or immunosuppressive/s in induction dose. Use of hydroxychloroquine was permitted in all groups. LIT values were compared using mixed models. Responsiveness was evaluated by standard response means (SRM) in groups with changes in DA (T2T, SLAQ) and EQ5D VAS as anchors. We did not have enough observations for stratified analysis for SLE patients with fibromyalgia. Results 1232/1364 (90%) were women, and 95% were Caucasian. Mean (SD) SLEDAI and SDI were 2.6 (3.5) and 0.7 (1.1) respectively. As (i) DA was low (median 2) in LDAS, (ii) steroid use was more prevalent in RONT than LDAS, we combined RONT and LDAS into one category to analyse patient relevant differences in LIT. LIT was responsiveness in the appropriate direction with improvement and worsening in disease activity (T2T and SLAQ) and health status (EQ5D VAS) over time. Mean LIT changes to and from NO to RONT/LDAS ranged from 3–5 (table 1), while it declined by over 8.5 with change from NO to ROFT. We had limited observations for ROFT to NO change. Mean change in LIT ranged from −3 to 3 with improvement and worsening in SLAQ, and from −7.6 to 6 with improvement and worsening in EQ5D VAS. Conclusions LIT responds appropriately in both directions to changes in physician (T2T) as well as patient relevant (DA and health status) outcomes among Spanish SLE patients. Funding Source(s): None

Background:Data on disease activity status and health status (HS) in clinical practice in Spain for patients with ankylosing spondylitis (AS) are scarce. The MIDAS study assessed the disease activity and the relationship with the reported HS in patients with AS treated in clinical practice in Spain.Objectives:This is a sub-analysis to evaluate the differences in disease activity and HS by gender of the patients with AS included in the MIDAS study.Methods:MIDAS is an observational, non-interventional, cross-sectional, multicenter study. Patients included were ≥18 years old with ≥6 months since diagnosis, were classified by ASAS and modified New York criteria; undergoing treatment ≥3 months. The primary variable was the disease control assessed by the percentage of patients in remission and low disease activity (measured by BASDAI and ASDAS-CRP)1-2.Results:We analyzed 313 AS patients; 237 (75.7%) were male and 76 (24.3%) female (Table 1). Disease control: According to BASDAI Table 1.Baseline demographic and clinical characteristics of the AS patients analysed.Total(n=313)Male(n=237)Female(n=76)Age (years), mean (SD)50.4 (12.0)50.1 (12.2)51.2 (11.5)Years since diagnosis, mean (SD)15.5 (11.6)16.8 (12.2)11.4 (8.5)Years since the symptoms’ onset to the study visit, mean (SD)20.5 (12.7)22.2 (13.0)15.2 (9.9)Years since the symptoms’ onset to diagnosis, mean (SD)5.0 (7.2)5.4 (7.7)3.9 (5.6)BMI (kg/m2), mean (SD)27.0 (4.9)27.5 (4.6)25.5 (5.6)Obesity (BMI>30), n (%)67 (23.0%)53 (23.7%)14 (20.9%)Smoking habitCurrent smoker, n (%)75 (24.0%)61 (25.7%)14 (18.4%)Ex-smoker (>6 months), n (%)81 (25.9%)68 (28.7%)13 (17.1%)Non-smoker, n (%)137 (43.8%)96 (40.5%)41 (53.9%)Family history of AS, n (%)66 (21.1%)48 (20.3%)18 (23.7%)Presence of HLA-B27, n (%)245 (78.5%)187 (79.2%)58 (76.3%)Patients previously treated with bDMARD99 (31.6%)77 (32.5%)22 (28.9%)Active disease, n (%)*BASDAI ≥4111 (35.5%)73 (30.8%)38 (50.0%) ASDAS-CRP ≥2.1133 (42.4%)99 (41.8%)34 (44.7%)CRP levels (mg/l), mean (SD)5.1 (8.2)5.7 (9.0)3.3 (4.3)PASS, n (%)270 (86.3%)208 (87.8%)62 (81.6%)ASAS-HI, mean (SD)5.8 (4.4)5.5 (4.4)6.8 (4.2)*Refers to the percentage of patients with active disease according to BASDAI≥4 and ASDAS-CRP ≥2.1.AS, ankylosing spondylitis; ASAS-HI, Assessment of Spondyloarthritis International Society - Health index; ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; bDMARD: biologic disease modifying anti-rheumatic drug; BMI, body mass index; CRP, C-reactive protein; HLA-B27, human leukocyte antigen B27; PASS, patient acceptable symptom state; SD, standard deviation.Conclusion:Our analysis showed a higher proportion of females with active disease when using the BASDAI definition. However, when using the ASDAS-CRP definition, these differences by gender seem to be less pronounced. Also, the impact of disease activity on the HS seems to be higher in females than males. As far as we know, this is the first Spanish study to evaluate gender in this patient population.References:[1]Smolen JS et al. Ann Rheum Dis 2018;77:3-17[2]Gratacós J et al. Reumatol Clin 2018;14:320-33Figure 1.Disease status by sex A)Disease control according to BASDAI B)Disease status according to ASDAS-CRPASDAS-CRP, Ankylosing Spondylitis Disease Activity Score- C-reactive protein; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index.Acknowledgements:We thank to MIDAS group investigators and patients included in the study.Disclosure of Interests:Cristina Fernández-Carballido Speakers bureau: I have received lectures fees from Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB., Consultant of: I have worked as a paid consultant for Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB., Jordi Gratacos-Masmitja Speakers bureau: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Lilly and Amgen., Consultant of: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Lilly and Amgen., Grant/research support from: During the course of the year I have received a private grand from Pfizer.I have not received any private influence in the elaboration of the contents of this talk., Eugenio de Miguel Speakers bureau: AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi., Paid instructor for: Janssen, Novartis, Roche, Consultant of: AbbVie, Novartis, Pfizer, Galapagos, Grant/research support from: Abbvie, Novartis, Pfizer, Pilar Susana Del Río Martínez Speakers bureau: Novartis, Pfizer, Janssen, Sanofi., Paid instructor for: Lilly, Consultant of: Lilly, Sanofi Aventis, Olga Martínez González Speakers bureau: Novartis, Antonio Fernandez-Nebro Speakers bureau: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Celgene, GSK, and Lilly, Consultant of: MSD, Pfizer, AbbVie, Janssen Cilag, Novartis, Celgene, GSK, and Lilly, Paloma Vela-Casasempere Speakers bureau: Astra-Zeneca, AbbVie, Boehringer, GSK, Novartis, UCB, Fresenius-Kabi, Sobi and Lilly, Consultant of: Astra-Zeneca, AbbVie, Boehringer, GSK, Novartis, UCB, Fresenius-Kabi, Sobi and Lilly, Grant/research support from: My unit has received also research support from Roche, MSD, Novartis, Lilly, BMS, and Fresenius-Kabi., Cristina Sanabra Employee of: Novartis employee, Carlos Sastré Employee of: Novartis employee.

Objectives:To describe the prevalence of subclinical atherosclerosis measured as carotid intima-media thickness (cIMT) in patients with rheumatoid arthritis (RA) and to analyze the associated factors.Methods:We performed an observational study of 60 patients with RA and 60 sex and age-matched controls. Patients with dyslipidemia were excluded. The main variable was the cIMT measured by ultrasound. The maximum cIMT was measured and atheromatous plaque was defined as focal thickening of the arterial wall protruding toward the lumen and measuring >0.5 mm or more than 50% of the neighboring cIMT. The other variables included were clinical and laboratory values, lipid metabolism, the 28-joint Disease Activity Score (DAS28), International Physical Activity Questionnaire (METs) and Adherence to a Mediterranean diet (MEDAS). Descriptive, bivariate and two multivariate models were constructed to identify factors associated with pathologic cIMT in all subjects and other in RA patients.Results:The baseline characteristics of both groups are shown in Table 1. The RA patients did not have differences in the mean (SD) of maximum cIMT in relation to the controls (0.77 [0.1] vs 0.75 [0.1]; p = 0.392), nor in the number of plaques (16 [26.7%] vs 10 [16.7]; p = 0.184). The factors associated with maximum cIMT in the total sample were male sex (ß= 0.182; p = 0.039), age (ß = 0.010; p Table 1.Baseline characteristics of 60 patients with RA and 60 controls.VariablePatients n=60Controls n=60p-valueAge in years, mean (SD)54.0 (11.1)54.2 (110.4)0.943Female sex; n (%)53 (88.3)51 (85.0)0.591Smoking0.300 Never smoked, n (%)27 (45.8)30 (54.5) Exsmoker, n (%)23 (39.0)14 (25.5) Active smoker, n (%)9 (15.3)11 (20,0)BMI (kg/m2), mean (SD)28.0 (5.5)27.3 (4.9)0.540MET-minute, median (IQR)533.2 (605.1)809 (716.9)0.028MEDAS, median (IQR)9.4 (1.8)9.1 (2.1)0.349Progression of RA, months, mean (SD)119.7 (84.1-170.5)--Diagnostic delay, months, median (IQR)5.7 (5.1-14.4)--Erosions, n (%)25 (43.1)--RF >10, n (%)45 (75.0)0 (0.0)ACPA >20, n (%)48 (80.0)0 (0,0)High-sensitivity CRP (mg/dl), median (IQR)8.1 (4.2)2.0 (4.5)0.009ESR (mm/h), median (IQR)21.1 (16.6)13.9 (12.3)0.008DAS28 at protocol, mean (SD)3.1 (2.2-4.2)--Synthetic DMARDs, n (%)52 (88.1)-- Methotrexate, n (%)36 (61.0)-- Leflunomide, n (%)6 (10.2)-- Sulfasalazine, n (%)7 (11.9)-- Hydroxychloroquine, n (%)4 (6.8)Biologic DMARDs, n (%)32 (54.2)-- Anti TNF-α, n (%)23 (39.0)-- Jak inhibitor, n (%)1 (1.7)-- Anti-IL-6, n (%)6 (10.2)-- Abatacept, n (%)1 (1.7)--Abbreviations: RA, rheumatoid arthritis; ACPA, anti-citrullinated peptide antibodies; RF, rheumatoid factor; SD, standard deviation; MEDAS: Mediterranean Diet Adherence Survey; DAS28, 28-joint Disease Activity Score; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; DMARD, disease-modifying antirheumatic drug; IL-6, interleukin 6; Anti TNF, anti–tumor necrosis factor.Conclusion:In patients with well-controlled established RA, subclinical atherosclerosis is associated, in addition to sex, age, and mediterranean diet, with inflammatory activity and ACPA value.Acknowledgements:Grant for Medical Researchers from “Fundación Española de Reumatología” 2019Grant from “Fundación Española de Reumatología” 2018 for non-funded projects.Disclosure of Interests:None declared

Background:IgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions that share pathogenic and molecular mechanisms [1] and may represent different outcomes of a continuous spectrum of disease [2]. Interleukin (IL)17A has been identified as a common genetic risk locus for several immune-mediated diseases [3, 4].Objectives:To determine whether IgAV and IgAN exhibit a different IL17A association pattern.Methods:Five IL17A tag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were genotyped in 388 Caucasian patients with IgAV, 99 patients with IgAN and 1,003 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and healthy controls and between patients with IgAN and healthy controls were observed when each IL17A genetic variant was analyzed independently (Table 1). Similarly, IgAV patients exhibited similar genotype and allele IL17A frequencies than those with IgAN (Table 1). Moreover, no genotype or allele differences between IgAV patients who developed nephritis and patients with IgAN were detected. Furthermore, haplotype frequencies were similar in patients with IgAV, IgAV and nephritis and those with IgAN.Table 1.Genotype and allele frequencies of IL17A gene in patients with IgA vasculitis, patients with IgA nephropathy and healthy controls.PolymorphismChangeData set1/11/22/212rs4711998G/AIgAV53.4 (207)38.9 (151)7.7 (30)72.8 (565)27.2 (211)IgAN49.0 (48)42.9 (42)8.2 (8)70.4 (138)29.6 (58)Controls52.7 (529)41.2 (413)6.1 (61)73.3 (1471)26.7 (535)rs8193036T/CIgAV57.0 (221)38.4 (149)4.6 (18)76.2 (591)23.8 (185)IgAN64.3 (63)31.6 (31)4.1 (4)80.1 (157)19.9 (39)Controls60.3 (605)35.2 (353)4.5 (45)77.9 (1563)22.1 (443)rs3819024A/GIgAV44.1 (171)43.3 (168)12.6 (49)65.7 (510)34.3 (266)IgAN39.4 (39)54.5 (54)6.1 (6)66.7 (132)33.3 (66)Controls45.6 (457)44.6 (447)9.9 (99)67.8 (1361)32.2 (645)rs2275913G/AIgAV44.6 (172)43.3 (167)12.2 (47)66.2 (511)33.8 (261)IgAN39.8 (39)53.1 (52)7.1 (7)66.3 (130)33.7 (66)Controls44.8 (449)44.2 (443)11.1 (111)66.8 (1341)33.2 (665)rs7747909G/AIgAV53.9 (209)39.4 (153)6.7 (26)73.6 (571)26.4 (205)IgAN41.1 (39)54.7 (52)4.2 (4)68.4 (130)31.6 (60)Controls53.0 (532)39.4 (395)7.6 (76)72.7 (1459)27.3 (547)Conclusion:Our results revealed that IgAV and IgAN share a similar IL17A association pattern.References:[1]N Engl J Med 2013;368:2402-14.[2]Am J Kidney Dis 1988;12:373-7.[3]Ann Rheum Dis 2014;73:1742-5.[4]Mediators Inflamm 2018;2018:1395823.Acknowledgements:This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by the European Regional Development Fund (ERDF) [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud; LL-G is supported by funds of IDIVAL [grant number INNVAL20/06]; RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CP16/00033].Disclosure of Interests:Diana Prieto-Peña: None declared, Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Leticia Lera-Gómez: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Javier Sanchez Perez: None declared, Diego de Argila: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galindez: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared

Objectives:To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) and identify risk factors associated with disease progression and mortality in patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD).Methods:We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main outcome measure at 60 months was worsening of FVC >10% or DLCO >15% and radiological progression or death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with worsening of ILD.Results:After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months. Baseline characteristics of 116 with RA-ILD treated with DMARDs is in table 1.The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (HR, 2.6 [95%CI, 1.0-6.7]), forced vital capacity (%) (HR, 3.8 [95%CI, 1.5-6.7]), anticitrullinated protein antibody titers (HR, 2.8 [95%CI, 1.1-6.8]), smoking (HR, 2.5 [95%CI, 1.1-6.2]), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 [95%CI, 0.2-0.8]). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%).Conclusion:Lung function is stable in most patients with RA-ILD receiving treatment with DMARDs, although one third of patients die. Identifying factors of worsening in RA-ILD is important for clinical management.Table 1.Baseline characteristics of 116 with RA-ILD treated with DMARDsVariableTotal=116Epidemiological characteristicsFemale sex, n (%)63 (54.3)Age, years, mean (SD)68.3 (9.9)Clinical and analytical characteristicsCurrent smokerNonsmoker, n (%)57 (49.1)Smoker, n (%)23 (19.8)Exsmoker, n (%)36 (31.0)Time since diagnosis of RA, months, median (p25-p75)148.5 (71.5-217.8)Diagnostic delay, months, median (p25-p75)8.5 (4.9-16.8)Time since diagnosis of ILD, months, median (p25-p75)27.5 (9.8-60.0)Positive rheumatoid factor (>10), n (%)111 (95.7)Positive ACPA titer (>20), n (%)100 (86.2)Erosive disease, n (%)76 (65.5)Treatment Synthetic DMARD100 (86.2) Methotrexate, n (%)51 (44.0) Leflunomide, n (%)30 (25.9) Sulfasalazine, n (%)9 (7.8) Hydroxychloroquine, n (%)21 (18.1)Biologic DMARD50 (43.1) Infliximab, n (%)1 (0.9) Etanercept, n (%)6 (5.2) Adalimumab, n (%)3 (2.6) Golimumab, n (%)3 (2.6) Certolizumab, n (%)3 (2.6) Tocilizumab, n (%)6 (5.2) Abatacept, n (%)15 (12.9) Rituximab, n (%)13 (11.2) Immunosuppressants11 (9.5) Mycophenolate, n (%)7 (6.0) Azathioprine, n (%)4 (3.4) Antifibrotic agents, nintedanib, n (%)1 (0.9) Baseline corticosteroids, n (%)69 (60.0) Dose of baseline corticosteroids, median (p25-p75)5.0 (0.0-7.5)Abbreviations. RA: rheumatoid arthritis; ILD: interstitial lung disease; ACPA: anticyclic citrullinated protein antibody; DMARD: disease-modifying antirheumatic drug; SD: standard deviation.Acknowledgements:Grant for Medical Researchers of the “Fundación Española de Reumatología” 2019. declare.Disclosure of Interests:None declared

OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in patients with SSc. However, the genetic factors involved in lung complication are not well defined. We aimed to review the association of the MIF gene, which encodes a cytokine implicated in idiopathic pulmonary hypertension among other diseases, with the susceptibility and clinical expression of SSc, in addition to testing the association of this polymorphism with SSc-related pulmonary involvement. METHODS: A total of 4392 patients with SSc and 16,591 unaffected controls from 6 cohorts of European origin were genotyped for the MIF promoter variant rs755622. An inverse variance method was used to metaanalyze the data. RESULTS: A statistically significant increase of the MIF rs755622*C allele frequency compared with controls was observed in the subgroups of patients with diffuse cutaneous SSc (dcSSc) and with pulmonary arterial hypertension (PAH) independently (dcSSc: p = 3.20E-2, OR 1.13; PAH: p = 2.19E-02, OR 1.32). However, our data revealed a stronger effect size with the subset of patients with SSc showing both clinical manifestations (dcSSc with PAH: p = 6.91E-3, OR 2.05). CONCLUSION: We reviewed the association of the MIF rs755622*C allele with SSc and described a phenotype-specific association of this variant with the susceptibility to develop PAH in patients with dcSSc.

Objective: To compare the prevalence of the main comorbidities in two large cohorts of patients with Primary Sjogren's Syndrome (pSS) and Systemic Lupus Erythematosus (SLE), with focus on cardiovascular (CV) diseases. Methods: Cross-sectional multicenter study where the prevalence of more relevant comorbidities in two cohorts was compared. Patients under follow-up from the SJOGRENSER (Spanish Rheumatology Society Register of pSS) and RELESSER (Spanish Rheumatology Society Register of SLE) registries, and who fulfilled the 2002-AECG and 1997-ACR classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when it was judged appropriate. Results: A total of 437 pSS patients (95% female) and 2,926 SLE patients (89% female) were included. Mean age: 58.6 (p55-p75: 50.0-69.9) and 45.1 years (36.4-56.3), respectively (p

Objective The objective of this study was to describe the demographic, clinical, and immunological manifestations of systemic lupus erythematosus (SLE) in male patients. Methods A cross-sectional, multicenter study was carried out of 3651 patients (353 men, 9.7%, and 3298 women, 90.2%) diagnosed with SLE, included in the Spanish Rheumatology Society SLE Registry (RELESSER). Results Mean ages (18–92 years) of symptom onset were 37 (SD 17) years (men) and 32 (SD 14) years (women). Male/female ratio was 1/9. Age of onset of symptoms and age at diagnosis were higher in men than in women ( p 50 years had a higher mortality (odds ratios 3.6 and 2.1, respectively). Furthermore, SLE patients who developed pulmonary hemorrhage, pulmonary hypertension, psychiatric involvement, complement deficiency, and hemophagocytic syndrome also had higher mortality, regardless of gender. Conclusion Patients with SLE over the age of 50 years have an increased risk of mortality. In Caucasians, age at diagnosis and symptom onset is higher in men than in women. The diagnostic delay is shorter in men. Male SLE patients present more cardiovascular comorbidities, and also more serositis, adenopathies, splenomegaly, renal involvement, convulsion, thrombosis, and lupus anticoagulant positivity than women.

Resumen Introduccion En los ultimos anos, el peso especifico de las consultas externas ha aumentado considerablemente. En la actualidad, la mayor parte de la atencion reumatologica se lleva a cabo en esta area del hospital. Sin embargo, apenas existe documentacion respecto a estandares de calidad asistencial. Objetivo Desarrollar, mediante consenso, estandares de calidad asistencial especificos para las consultas externas de reumatologia. Metodo El proyecto se llevo a cabo mediante metodologia Delphi a 2 rondas. Se conto con la participacion de un comite cientifico (13 reumatologos), 5 grupos nominales (45 reumatologos y 12 enfermeras especializadas) y un grupo de discusion formado por 9 pacientes. Se generaron de forma sucesiva diversos borradores hasta obtener un documento final que incluyo los estandares que recibieron una puntuacion igual o superior a 7 en al menos el 70% de los participantes. Resultados El documento consta de 148 estandares distribuidos en 9 areas tematicas: a) estructura (22); b) actividad clinica y relacion con los pacientes (34); c) planificacion (7); d) niveles de prioridad (5); e) relacion con atencion primaria, con el servicio de urgencias y con otros servicios del hospital (20); f) proceso (26); g) enfermeria (13); h) docencia e investigacion (13), e i) computo de actividad (8). Conclusion Se han consensuado unos estandares de calidad asistencial que pueden ser utiles para organizar la actividad en las consultas externas de los servicios de reumatologia y servir como marco de referencia a la hora de elevar propuestas de mejora a la gerencia del hospital o a otros estamentos de la administracion.

Objective Rheumatoid factor (RF) is a well-established diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, ∼20% of RA patients are negative for this anti-IgG antibody. To date, only variation at the HLA-DRB1 gene has been associated with the presence of RF. This study was undertaken to identify additional genetic variants associated with RF positivity. Methods A genome-wide association study (GWAS) for RF positivity was performed using an Illumina Quad610 genotyping platform. A total of 937 RF-positive and 323 RF-negative RA patients were genotyped for >550,000 single-nucleotide polymorphisms (SNPs). Association testing was performed using an allelic chi-square test implemented in Plink software. An independent cohort of 472 RF-positive and 190 RF-negative RA patients was used to validate the most significant findings. Results In the discovery stage, a SNP in the IRX1 locus on chromosome 5p15.3 (SNP rs1502644) showed a genome-wide significant association with RF positivity (P = 4.13 × 10(-8) , odds ratio [OR] 0.37 [95% confidence interval (95% CI) 0.26-0.53]). In the validation stage, the association of IRX1 with RF was replicated in an independent group of RA patients (P = 0.034, OR 0.58 [95% CI 0.35-0.97] and combined P = 1.14 × 10(-8) , OR 0.43 [95% CI 0.32-0.58]). Conclusion To our knowledge, this is the first GWAS of RF positivity in RA. Variation at the IRX1 locus on chromosome 5p15.3 is associated with the presence of RF. Our findings indicate that IRX1 and HLA-DRB1 are the strongest genetic factors for RF production in RA.

Resumen Objetivo Evaluar la efectividad, seguridad y coste de rituximab en pacientes con artritis reumatoide (AR) dependiendo de la dosis utilizada. Material y metodos Estudio observacional retrospectivo. Se incluyo a 52 pacientes con AR tratados al menos con una dosis de rituximab durante 135,3 pacientes-ano. Se obtuvieron 3 grupos de tratamiento: G1, primer curso y siguientes de 2 infusiones de 1 g separadas 15 dias; G2, primer curso de 2 infusiones de 1 g seguido por cursos de 2 infusiones de 500 mg, y G3, primer curso y siguientes de 2 infusiones de 500 mg separadas por 15 dias. Los retratamientos fueron a demanda segun la clinica. Se analizaron por grupos: el tiempo retencion (Log-Rank), las tasas de retratamientos y de eventos adversos (razon de tasas de incidencia) y los costes del tratamiento por paciente-mes de rituximab. Resultados El grupo 2 mostro una mejor relacion coste-efectividad que el grupo 1 ya que se asocio a una mayor retencion de rituximab (media [IC del 95%] 65,7 [60,8-70,7] meses vs. 33,5 [22,7-44,3]; p Conclusiones El uso de rituximab a dosis completa al inicio seguido de dosis reducida en los sucesivos cursos administrados a demanda parece la opcion mas coste-efectiva.

Objective Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Material and methods Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1 g infusions separated by 15 days; (G2) First course 2 infusions of 1 g followed by 2 infusions of 500 mg; (G3) First course and followed by 2 infusions of 500 mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analyzed by groups. Results Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8–70.7] months vs 33.5 [22.7–44.3]; P Conclusions The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option.

OBJECTIVE RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach. METHODS A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry. RESULTS In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P < 5×10(-4) and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19×10(-8)]. CONCLUSIONS SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants.

Objectives: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. Patients and methods: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving disease-modifying antirheumatic drugs (DMARDs) between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main endpoint was “Progression to ILD at the end of follow-up” in terms of the following outcomes: (1) improvement (i.e., improvement in forced vital capacity (FVC) ≥ 10% or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 15% and absence of radiological progression), (2) nonprogression (stabilization or improvement in FVC ≤ 10% or diffusing capacity of the lungs for carbon monoxide (DLCO) &lt, 15% and absence of radiological progression), (3) progression (worsening of FVC &gt, 10% or DLCO &gt, 15% and radiological progression), or (4) death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with the worsening of ILD. Results: After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months after diagnosis of ILD. The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (hazard ratio (HR), 2.6 (95%CI, 1.0–6.7)), FVC &lt, 80% (HR, 3.8 (95%CI, 1.5–6.7)), anticitrullinated protein antibody titers (HR, 2.8 (95%CI, 1.1–6.8)), smoking (HR, 2.5 (95%CI, 1.1–6.2)), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 (95%CI, 0.2–0.8)). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%). Infection was fatal in 10/18 patients (55.5%) during follow-up. Conclusions: Lung function is stable in most patients with RA-ILD receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs), although one-third worsened or died. Identifying factors associated with worsening in RA-ILD is important for clinical management.

Background:Metotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA) both in monotherapy and in combination with biologic disease-modifying antirheumatic drugs (bDMARDs), it usually well tolerated but AEs may appear that causing toxicity that requires suspension of the treatmentObjectives:Determine the prevalence of certain polymorphisms among patients that receive bDMARD in monotherapy or in combination with MTX to confirm its relevance as biomarkers of intolerance. Evaluate the influence of certain polymorphisms in the effectiveness of monotherapy or combined treatment in patients, through“Disease Activity Score 28”(DAS28), SDAI Simple disease activity index (SDAI), Clinical disease activity index (CDAI) and each one of its componentsMethods:Retrospective observational multicentric study (University Hospital Complex, Granada, Carlos de Haya Hospital, Malaga and University Hospital Reina Sofia, Cordoba), of cases-control of 227 patients with RA (criteria ACR/EULAR), of which 120 received MTX and bDMARD combined therapy (cases) and other with only bDMARD (controls). All of them had been or were currently treated with MTX, remained with stable doses of bDMARD, and had a DNA sample stored before the inclusion in the studyDNA was isolated from total peripheral blood and by fluorescent probe HybProbe and/ or Taqman, 10 polymorphisms of 10 protein coding genes were determined involved in the metabolism and toxicity of MTX according to current evidenceBesides the type of polymorphism, data on the activity of the disease were analysed (DAS28VSG, DAS28PCR, SDAI, CDAI, at the start of the MTX income, of the BT, and in the inclusion visitA descriptive and comparative study was carried out on all that and afterwards an assessment was made through a multiple logistic regression analysis (MLR) on the risk of intolerance to MTXResults:An analysis was carried out on 227 patients (120 cases and 107 controls) with an average age of 60 (12,1) being women 78,4%, with a time of evolution since diagnosis of 14,84 (7,78) years48,9% registered adverse events (AE) MTX related, mainly gastrointestinal, hepatobiliary and skin-subcutaneous tissue. The percentage of AE appearance was superior in the monotherapy group than in the group with combined therapyThe most prevalent polymorphism (84,6% (IC95%: 84,09%-85,11%) and in cases (86,0% (IC95%: 79,43%-92,57%) washomozygous CC (ITPase-c94a); in controlshomozygous GG (GGH-T401C) (87,5% (IC95%:81,58%-93,42%)There were no significant differences in the parameters of activity between groups, in both, patients were best basally controlled than at the start of the MTX income and/or bDMARDBeinghomozygous-AA for the DHFR genewas significantly associated (pIn MLR,homozygous GG(ref. heterozygous AG) in polymorphismGGH-T401C,beinghomozygous CC(ref. heterozygous TC) in polymorphismABCC2-C24TandPCR (mg/dL) at the start of bDMARDresulted independent predictive factors of MTX intoleranceConclusion:Polymorphisms T401C for the GGH gene and C24T for the ABCC2 gene and PCR at the start of the bDMARD resulted independent predictive factors of MTX intolerance. Polymorphismhomozygous AAforDHFR genewas related to significant protection against appearance of AEDisclosure of Interests:Alejandro Escudero Contreras: None declared, Rafaela Ortega Castro: None declared, Jerusalem Calvo Gutierrez: None declared, Natalia Mena-Vázquez: None declared, Rafael Cáliz Cáliz: None declared, Eduardo Collantes Estevez Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene, Antonio Fernandez-Nebro: None declared, Maria del Carmen Abalos-Aguilera: None declared, Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Mª Teresa Ruiz Jimenez Employee of: Roche Farma, SPAIN, Font Ugalde Pilar: None declared

Background:Objectives:To study the frequency of polyautoinmunity and multiple autoinmune syndrome (MAS) in patients with rheumatoid arthritis (RA) and systemic lupus erithematosus (SLE).Methods:Study design: We performed a cross-sectional study in patients with RA and SLE, and compared them with healthy subjects. Cases: RA patients classified by ACR/EULAR 2010 criteria and SLE patients classified by ACR/EULAR 2019 criteria. SLE and RA patients were compiled consecutively from a rheumatology clinic of the Regional University hospital of Malaga. Controls: subjects without rheumatologic autoimmune disease (AD) from the same population area. Protocol: All subjects filled out a predesigned questionnaire for the collection of polyautoimmunity data on the cut-off date. Main variables: polyautoimmunity was defined as co-occurrence of SLE or RA and other AD. Secondary variables: Rheumatologic, cutaneous, endocrine, digestive and neurological AD. MAS was defined as presence of three or more AD. Family history of SLE, RA and other autoimmune diseases were also collected. Statistic analysis: descriptive analysis, bivariate analysis and multivariable analysis were done. (Dependent variable: Polyautoimmunity).Results:We recruited 109 patients with RA, 105 with SLE and 88 controls. Fifteen patients with RA (13.8%), 43 with SLE (41%) and 2 controls (2.2%) reported polyautoimmunity. Table 1 describes the epidemiological characteristics, comorbidities and polyautoimmunity in study population. The most frequent AD associated with RA was Sjögren’s syndrome (SS) (53.3%) and SS (55.8%) followed by the antiphospholipid syndrome (30.2%) were associated with SLE. Hashimoto’s thyroiditis and psoriasis were the next most frequent AD. According to family history, 5 patients with RA (33.3%) and 12 with SLE (27.9%) had a family history of first degree of other AD. Obesity was associated with polyautoimmunity in RA (OR = 3,362, p = 0.034). In SLE, joint damage (OR = 2.282, p = 0.038) and anti-RNP antibodies (OR = 5.095, p = 0.028) were factors associated with polyautoimmunity and taking hydroxychloroquine was a protective factor (OR = 0.190, p = 0.004).Conclusion:Polyautoimmunity in RA and especially in SLE is frequent. It was associated with obesity in RA and in SLE with joint damage and anti-RNP antibodies. The hydroxychloroquine appeared as a protective factor.VariablesRA(N=109)SLE(N=105)Controls(N=88)P valueEpidemiological characteristicsSex: female, n (%)85 (78.0)99 (94.3)68 (77.3)0.001Age, mean (SD), years56.5 (10.8)50.8 (13.2)57.1 (10.6)0.133Caucasic race, n (%)107 (98.2)105 (100)88 (100)0.168ComorbiditiesSmoking0.001 No smoking, n (%)55 (50.5)78 (74.3)56 (63.6) Smoking history, n (%)54 (49.5)27 (25.7)32 (36.4)Obesity, n (%)38 (34.9)21 (20.0)22 (25.0)0.044Dyslipidemia, n (%)24 (22.0)22 (21.2)17 (19.3)0.896Hypertension, n (%)27 (24.8)28 (26.7)23 (26.1)0.746Diabetes mellitus, n (%)7 (6.4)1 (1.0)1 (1.1)0.031Polyautoimmunity, n (%)15 (13.8)43 (41)2 (2.2)MAS, n (%)1 (0.9)9 (8,6)0 (0.0)FH polyautoimmunity, n (%)19 (17.6)26 (24.8)15 (17.0)0.060RA: rheumatoid arthritis; SLE: systemic lupus erithematosus; SD: standard desviation; MAS: multiple autoinmune syndrome; FH:Family historyDisclosure of Interests:None declared