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Objective To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. Patients and methods Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n = 79) or Enbrel® (n = 59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52 weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. Results No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95% CI] at 12.0 months [10.2–12.0] for the biosimilar and 12.0 months [12.0–12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52 weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55 € (1,747.20 €/patient-years) for the hospital. Conclusion The biosimilar Benepali is as effective and safe as the original and much more cost-effective.

Objective To assess the effectiveness, safety and cost of Etanercept biosimilar in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) compared to the standard drug in real clinical practice. Patients and methods Retrospective observational study. Case series of 138 patients with RA, SpA or PsA treated with at least one dose of Benepali® (n = 79) or Enbrel® (n = 59). Drug retention time was the primary efficacy endpoint compared to the biosimilar and the original. The proportion of patients achieving low disease activity or remission after 52 weeks was used as the secondary outcome. Safety was assessed by means of the adverse effects incidence rate. A cost minimization analysis was performed. Results No differences were observed regarding treatment retention time between drugs (median [95% confidence interval, 95% CI] at 12.0 months [10.2-12.0] for the biosimilar and 12.0 months [12.0-12.0] for the original). Similar improvements, in terms of inflammatory activity and physical function, were obtained after 52 weeks except for patients with SpA and PsA who, in general, experienced improvements of BASDAI and ASDAS with the original compared with the biosimilar. No significant differences were observed in the total number of adverse effects (.43 events/patient-years versus the biosimilar and .53 versus the original). Using the biosimilar in place of the original drug resulted in a net savings of 118,383.55 € (1,747.20 €/patient-years) for the hospital. Conclusion The biosimilar Benepali is as effective and safe as the original and much more cost-effective.

A human motion capture system using an RGB-D camera could be a good option to understand the trunk limitations in spondyloarthritis. The aim of this study is to validate a human motion capture system using an RGB-D camera to analyse trunk movement limitations in spondyloarthritis patients. Cross-sectional study was performed where spondyloarthritis patients were diagnosed with a rheumatologist. The RGB-D camera analysed the kinematics of each participant during seven functional tasks based on rheumatologic assessment. The OpenNI2 library collected the depth data, the NiTE2 middleware detected a virtual skeleton and the MRPT library recorded the trunk positions. The gold standard was registered using an inertial measurement unit. The outcome variables were angular displacement, angular velocity and lineal acceleration of the trunk. Criterion validity and the reliability were calculated. Seventeen subjects (54.35 (11.75) years) were measured. The Bending task obtained moderate results in validity (r = 0.55–0.62) and successful results in reliability (ICC = 0.80–0.88) and validity and reliability of angular kinematic results in Chair task were moderate and (r = 0.60–0.74, ICC = 0.61–0.72). The kinematic results in Timed Up and Go test were less consistent. The RGB-D camera was documented to be a reliable tool to assess the movement limitations in spondyloarthritis depending on the functional tasks: Bending task. Chair task needs further research and the TUG analysis was not validated. Graphical abstract Comparation of both systems, required software for camera analysis, outcomes and final results of validity and reliability of each test.

espanolEl registro de lupus de la Sociedad Espanola de Reumatologia (RELESSER) es un registro multicentrico de pacientes con lupus eritematoso sistemico seguidos en servicios de reumatologia espanoles, que contiene cuantiosa informacion sobre 4.024 pacientes. Hasta la fecha han sido publicados 14 analisis sobre la fase transversal del registro. Se describen los resultados mas relevantes, a criterio de los autores, concernientes a las caracteristicas clinicas acumuladas, nivel de actividad, tratamientos, refractariedad, dano y mortalidad. Se revisan asimismo los resultados de analisis especificos sobre el lupus incompleto, la nefritis lupica, las manifestaciones respiratorias, los eventos cardiovasculares, las infecciones graves, las neoplasias, la fibromialgia, el lupus en varones, el lupus en latinoamericanos y el lupus de inicio juvenil, comparando los diferentes subgrupos con el total de la cohorte. RELESSER se ha constituido como uno de los registros clinicos de lupus eritematoso sistemico mas importantes del mundo, resultando altamente productivo en terminos de generacion de conocimiento de la enfermedad en pacientes espanoles, util tambien para toda la comunidad cientifica. EnglishThe lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors’ perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

The lupus register of the Spanish Society of Rheumatology (RELESSER) is a multicentre register of patients with systemic lupus erythematosus (SLE) under follow-up by Spanish Rheumatology Services. It contains data on a total of 4024 patients with SLE. So far, 14 studies have been published from the transversal phase of RELESSER. Here we report the more relevant contributions of those studies, according to the authors' perspective, concerning cumulative clinical characteristics, level of activity, treatments, refractory disease, damage and mortality. We also review the main results of the analysis regarding incomplete SLE, lupus nephritis, respiratory manifestations, cardiovascular disease, serious infection, malignancies, fibromyalgia, SLE in males, SLE in Hispanics and juvenile-onset SLE, comparing the main characteristics of each subgroup to the global cohort. RELESSER has become one of the most important clinical SLE registers around the world, with a high yield in terms of knowledge generation about the disease in Spain, also useful for the entire scientific community.

BACKGROUND/OBJECTIVES Immune-mediated inflammatory diseases (IMIDs) are prevalent diseases. There is, however, a lack of understanding of the link between diet and IMIDs, how much dietary patterns vary between them and if there are food groups associated with a worsening of the disease. SUBJECTS/METHODS To answer these questions we analyzed a nation-wide cohort of n = 11,308 patients from six prevalent IMIDs and 2050 healthy controls. We compared their weekly intake of the major food categories, and used a Mendelian randomization approach to determine which dietary changes are caused by disease. Within each IMID, we analyzed the association between food frequency and disease severity. RESULTS After quality control, n = 11,230 recruited individuals were used in this study. We found that diet is profoundly altered in all IMIDs: at least three food categories are significantly altered in each disease (P

Objectives To study the differences between rheumatoid arthritis (RA)-interstitial lung disease (ILD) patients and RA patients without ILD in severity markers and disease activity and to identify factors associated with the presence of ILD in RA patients. Patients and methods Patients: RA-ILD patients selected from a multicentre cohort in Andalusia, Spain. Controls: RA-patients without ILD paired by sex, age and disease duration. Protocol: RA patients are reviewed every 3–6 months in rheumatology consultation. All patients are reviewed according to a predetermined protocol with systematic data collection. Outcomes: description of ILD type, differences in severity markers and disease activity in both groups. Other variables: ILD type by imaging technique (HRCT): nonspecific interstitial pneumonia (NSIP)/usual interstitial pneumonia (UIP). Lung function by PTF. Activity and severity markers of arthritis by DAS28-ESR, HAQ, RF, ACPA and erosions. Treatment with DMARD. Statistical analysis: descriptive and paired T-test or Chi-square test followed by binary logistic regression (DV: ILD in patients with RA). Results Eighty-two patients were included, 41 RA-ILD and 41 RA controls. RF and ACPA positivity, serositis and osteoporosis were more frequent in RA-ILD patients. No significant differences in DAS28 were observed (P = .145) between RA-ILD and RA control patients. RA-ILD patients presented worse HAQ scores (P = .006). All patients were treated with disease modifying antirheumatic drugs (DMARDs). The risk of developing ILD in RA patients is tripled by a history of smoking or the presence of erosive arthritis (R2 = .36). Conclusions The results of our study support the higher frequency of UIP and NSIP in RA patients. DLCO is the most sensitive parameter to detect ILD in RA patients. Our study showed that ILD in RA patients was associated with RA severity (presence of erosions and ACPA) and with a history of smoking.

To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution computed tomography (HRCT) PATIENTS AND METHODS: We performed a cross-sectional, observational study in patients with RA-ILD (cases) controlled with a group of RA patients without ILD (controls) paired by sex, age, and time of disease evolution. Patients were assessed using HRCT, PFT, and US. The main variables were B-line number, evaluation of the lung-US score already described, pleural irregularities, and A pattern US lost. ROC curve analysis was performed to establish the cut-off point of the US B-lines number for detecting the presence of significant RA-ILD in relation to HRCT, and logistic regression analysis was performed to identify the intercostal spaces.Seventy-one patients were included, 35 (49.2%) with ILD-RA and 36 (50.8%) RA controls. Regarding US score, we found that the detection of 5.5 lines in a reduced score of 8 intercostal spaces had a sensitivity = 62.2%, specificity = 91.3%, PPV = 88.4%, and NPV = 69.5%. In multivariate analysis, the intercostal spaces which showed independent association with ILD were 3rd right anterior axillary space (OR [IC 95%] 19.0 [1.3-27.5]), 8th right posterior axillary space (OR [IC 95%] 0.04 [0.0-0.6]), 8th right subscapular space (OR [IC 95%] 16.5 [1.8-45.5]), 9th right paravertebral space (OR [IC 95%] 7.11 [1.0-37.1]), and 2nd left clavicular middle space (OR [IC 95%] 21.9 [1.26-37.8]).Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. A 8-space reduced score showed a similar total predictive capacity than 72-space score. Key Points • Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. • The 72-space evaluation is highly sensitive, whereas a simplified score enables a more specific and faster diagnosis. • The number of B lines is correlated with DLCO, ACPA, inflammatory activity, and physical function.

Background Studies in axial spondyloarthritis (AxSp) have shown that intensity of pain, anxiety, depression and inflammatory activity are associated with poor sleep quality. Aim To describe mood and sleep disorders and positive psychological factors in patients with AxSp and psoriatic arthritis (PsA) and to evaluate the psychological factors that are potentially involved in sleep disorders. Design Multicenter cross-sectional observational study based on a series of patients with AxSp and PsA. Participants Participants were selected consecutively from patients aged ≥18 years with AxSp or PsA followed at the rheumatology department of 4 Spanish hospitals. Inclusion criteria age ≥18 years, AxSp (ASAS criteria) or PsA (CASPAR criteria), ability to understand the study and prepared to complete the questionnaires. Methods Main outcomes: Oviedo Sleep Quality questionnaire result. Secondary outcomes psychological status evaluated using the Hospital Anxiety and Depression Scale (HADS) questionnaire, health-related quality of life evaluated using SF-36, perception of pain evaluated using the short questionnaire for assessment of pain (BDU) and fatigue evaluated using the Fatigue Scale (FACIT) questionnaire. We performed a descriptive multivariate linear regression analysis to study factors that were independently associated with sleep disorders. The STROBE guidelines were adopted. Results We included 301 patients (152 [50.5%] with AxSp and 149 [49.5%] with PsA). The multivariate linear regression analysis for the whole sample showed that insomnia was inversely associated with emotional recovery and biologic disease-modifying antirheumatic drugs and directly associated with depression in both groups. The analysis by disease (AxSp and PsA) showed that insomnia was independently associated with depression and emotional recovery. Conclusions Insomnia may be associated with other mood disorders, quality of life and inflammatory activity in the patients studied here. Relevance to clinical practice A nurse intervention can be carried out to prevent sleep disorders knowing the consequences and triggers of the problem.

Objectives To describe the therapeutic management of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) in patients initiating treatment with biological agents. Materials and methods Observational, retrospective, longitudinal study in 33 Spanish hospitals. Patients with RA, PsA and AS starting treatment with biological agents between September 2009 and August 2010 and a follow-up longer than 3 years were included. Clinical-demographic characteristics, drugs, biological therapy survival, and reasons for discontinuation or switching were analysed. Results Four hundred and sixty-three patients were included (183 RA, 119 PsA and 161 AS), with a mean follow-up of 3.8 years. At the end of follow-up, a high proportion continued with the first biological prescribed (41.0% of RA, 59.7% of PsA and 51.6% of AS), 31.1%, 47.9% and 42.9% of RA, PsA and AS patients requiring dosage adjustments, respectively. There was temporary discontinuation in 8.2%, 8.4% and 15.5% of patients, and a switch of biologic agent was required in 37.7%, 26.1% and 24.2%. Definitive discontinuation occurred in 13.1%, 5.9% and 8.7% of RA, PsA and AS patients, respectively. Mean time to discontinuation or switching was 30.1 months for RA and 35.7 months for PsA and AS. Conclusions Our results suggest that, in practice, half of patients with RA and two thirds with PsA or AS maintained the first biological, but with frequent dose adjustments.

OBJECTIVE To evaluate cognitive function in adult patients with juvenile idiopathic arthritis (JIA) and associated factors. PATIENTS AND METHODS We performed a cross-sectional observational study of adult patients with JIA and a healthy control group (no inflammatory diseases) matched for age, gender, and educational level. Cognitive function was assessed using Wechsler Adult Intelligence Scale-III. The cognitive domains measured were attention/concentration, verbal function, visuospatial organization, working memory, and problem solving (Similarities). Other measures included clinical-epidemiological characteristics, comorbid conditions, and treatment. We performed a descriptive bivariate analysis and logistic regression to identify factors associated with visuospatial involvement. RESULTS The study population comprised 104 subjects (52 with JIA and 52 healthy controls). Patients with JIA had poorer results for visuospatial function, with a lower median scaled score on the Block Design test (5.0 [4.0-8.0] vs 8.0 [5.0-10.0]; P = .014). The number of patients with scaled scores below the average range (

Objective To describe the frequency of polyautoimmunity and multiple autoimmune syndrome in patients with rheumatoid arthritis (RA) and patients with systemic lupus erythematosus (SLE). Patients and methods This was a cross-sectional observational study of patients with RA, SLE, and controls without autoimmune rheumatic disease. Cases were those with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria and SLE according to the 2019 American College of Rheumatology/European League Against Rheumatism criteria, consecutively recruited in a rheumatology clinic. Controls were subjects with no rheumatic autoimmune disease (AIDs) recruited in the same area. Patients filled out a questionnaire on polyautoimmunity. Variables of interest were polyautoimmunity (RA or SLE with other AIDs), whereas secondary variables were rheumatic, skin, endocrine, digestive, and neurological AIDs. Multiple autoimmune syndrome is defined as the presence of 3 or more AIDs and a family history of AIDs. Statistical analyses performed were descriptive, bivariate, and multivariate (dependent variable: polyautoimmunity). Results The study population comprised 109 patients with RA, 105 patients with SLE, and 88 controls. Polyautoimmunity was recorded in 15 patients with RA (13.8%), 43 with SLE (41%), and 2 controls (2.2%). The most frequent AID in RA was Sjogren syndrome (53.3%), followed by Hashimoto thyroiditis and psoriasis; the most frequent AIDs in SLE were Sjogren syndrome (55.8%) and antiphospholipid syndrome (30.2%), followed by Hashimoto thyroiditis. Obesity was associated with polyautoimmunity in RA (odds ratio [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 risk factors for polyautoimmunity, and hydroxychloroquine was a protective factor (OR, 0.190; p = 0.004). Conclusions Polyautoimmunity is frequent in RA and even more frequent in SLE. It was associated with obesity in RA and with joint damage and anti-RNP in SLE. Hydroxychloroquine was a protector.

To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) on the outcome of interstitial lung disease secondary to rheumatoid arthritis (RA-ILD).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 changed 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.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%).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. Key Points • We have performed prospectively evaluated lung and joint function in patients with RA-ILD receiving treatment with various DMARDs. • In our study, the lung function is stable and inflammatory activity well controlled in most patients with RA-ILD receiving treatment with DMARDs. • Neither csDMARDs nor anti-TNF agents were associated with a significant risk of worsening of lung disease, whereas non-anti-TNF bDMARDs could reduce the risk of worsening of lung disease. • Smoking and poor control of joint involvement were the main factors associated with worsening of lung disease.

Objectives: To compare the ability to participate in social activities among rheumatoid arthritis patients with other rheumatic disease patients and identify potentially implicated factors. Patients and methods: Between June and November 2019, we consecutively selected patients aged ≥18 years with RA (defined according to ACR/EULAR 2010), SpA (ASAS/EULAR 2010), and SLE (ACR 1997). Main outcome measures: Ability to participate in social roles and activities evaluated using the PROMIS score v2.0 short-form 8a (PROMIS-APS). Secondary outcomes: Participation in social activities according to a series of variables (mobility, depression, satisfaction with social relationships, social isolation, company, emotional support, instrumental support, and support via information). We evaluated the association between the ability to participate in social activities and associated variables using multivariable linear regression analysis. Results: The study population comprised 50 patients with RA (33.1%), 51 patients (33.8%) with SpA, and 50 patients (33.1%) with SLE. The mean PROMIS-APS scores were similar in the three groups. The multivariable analysis for the whole sample showed that the ability to participate in social activities was inversely associated with depression and directly with social satisfaction, mobility, company, and age. The stratified analysis revealed an inverse association between inflammatory activity and ability to participate in social activities in patients with RA and SpA, but not in those with SLE. Conclusion: All patients with RA, SpA, and SLE had a similar ability to participate in social activities. This was associated with other psychosocial factors (social satisfaction, mobility, company, depression) and clinical factors (age and inflammatory activity).

Objectives: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. Patients and methods: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) &gt, 10% or diffusing capacity of the lungs for carbon monoxide &gt, 15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. Results: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8–93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3–2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0–2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4–3.9]), and smoking (HR, 2.7 [95%CI, 1.6–4.7]). Conclusion: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.

Objective Sarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective of this post hoc analysis was to compare the efficacy of sarilumab (200 mg every 2 weeks) monotherapy (MONARCH study) with that of sarilumab and MTX combination therapy (MOBILITY study) at week 24. Methods The endpoints assessed were mean change from baseline in the Clinical Disease Activity Index (CDAI), 28-joint Disease Activity using CRP (DAS28-CRP), CRP, haemoglobin (Hb), pain visual analogue scale (VAS) and Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue. Least square (LS) mean change from baseline (95% CI) at week 24 for all endpoints was compared between the treatment arms for adjusted comparisons. Results This analysis included 184 patients on sarilumab monotherapy and 399 patients on sarilumab plus MTX. Differences (P Conclusion This analysis demonstrated that the efficacy of sarilumab monotherapy was similar to that of sarilumab and MTX combination therapy.

Objective: To identify factors associated with the higher proportion of fatty tissue and overweight/obesity observed in patients with juvenile idiopathic arthritis (JIA). Patients and methods: We performed a cross-sectional study of 80 JIA patients aged 4–15 years with 80 age- and sex-matched healthy controls. Body composition was assessed using dual-energy x-ray absorptiometry. The 27-joint Juvenile Arthritis Disease Activity score (JADAS27) was calculated. Two multivariate models were constructed to identify factors associated with overweight/obesity and fat mass index (FMI). Results: No differences were found between cases and controls in body mass index (BMI) or body composition. However, compared with controls, patients with a high inflammatory activity (JADAS27 &gt, 4.2 for oligoarticular JIA or &gt, 8.5 for polyarticular disease) had higher values for BMI (p = 0.006), total fat mass (p = 0.003), FMI (p = 0.001), and fat in the legs (p = 0.001), trunk (p = 0.001), and arms (p = 0.002). The factors associated with overweight/obesity in patients were the duration of therapy with biological drugs, measured in months (OR [95% CI] = 1.12 [1.02–1.04], p = 0.037), and physical activity (OR [95% CI] = 0.214 [0.07–0.68], p = 0.010), while the factors associated with FMI were age (β [95% CI] = 0.30 [0.17–1.41], p = 0.014), JADAS27 (β [95% CI] = 0.45 [0.16–1.08], p = 0.009), and physical activity (β [95% CI] = −0.22 [−5.76 to 0.29], p = 0.031). Conclusion: Our study revealed no differences between JIA patients with well-controlled disease and low disability and the healthy population in BMI or body composition. Furthermore, the association observed between inflammatory activity and adiposity could be responsible for poorer clinical course.

espanolObjetivo Revisar la eficacia y seguridad del rituximab en neuropatia vasculitica (NV). Metodos Se realizo una busqueda en la literatura de Medline y Embase hasta 2017. Los terminos incluidos guardaron relacion con «vasculitis», «neuropatia vasculitica» y «rituximab». Dicha busqueda fue realizada por 2 revisores. El resultado principal fue la eficacia del rituximab. Resultados Tras seleccionar inicialmente 702 articulos, 5 de ellos permanecieron con un nivel de evidencia de entre 1+ y 3, y un grado de recomendacion variable. En el unico ensayo clinico incluido, el rituximab fue superior a la terapia convencional para vasculitis crioglobulinemica, mostrando NV un incremento en la tasa de retencion farmacologica (64,3 vs. 3,5%; p Conclusiones Rituximab parece ser un tratamiento eficaz y seguro para NV, en el contexto de vasculitis crioglobulinemica. Se carece de evidencia sobre la eficacia especifica de NV en el contexto de otras vasculitis. EnglishObjective To review the efficacy and safety of rituximab in vasculitic neuropathy (VN). Methods A literature search was performed on Medline and Embase up until 2017. It included terms related to “vasculitis”,“vasculitic neuropathy” and “Rituximab”. Research was carried out by two reviewers. The main outcome was rituximab efficacy. Results Of an initial selection of 702 articles, 5 remained with a level of evidence between 1+ and 3 and variable recommendation degree. In the only clinical trial included, rituximab was superior to conventional therapy for cryoglobulinemic vasculitis with VN showing an increase in drug retention rate (64.3% vs. 3.5%; P Conclusions Rituximab seems an effective and safe treatment for VN in the context of cryoglobulinemic vasculitis. Evidence for specific efficacy in VN in the context of other types of vasculitis is lacking.

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.

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

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients.Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions.Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort.Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, 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.

Resumen OBJETIVO: Describir si las enfermedades inflamatorias reumaticas (EIR) se asocian con mayor riesgo de hospitalizacion y/o mortalidad por COVID-19 e identificar los factores asociados a la hospitalizacion y mortalidad en EIR y COVID-19 en diferentes Hospitales de Andalucia METODOS: Diseno: Estudio multicentrico observacional de casos y controles Pacientes: Casos: EIR y COVID-19 de diferentes centros de Andalucia Controles: pacientes sin EIR pareados por sexo, edad y PCR-COVID Protocolo: se solicito al servicio de microbiologia un listado de pacientes con PCR para COVID-19 desde 14 de marzo al 14 de abril de 2020 Se identificaron los pacientes que tuvieran EIR y luego consecutivamente un control pareado para cada caso Variables: La variable de desenlace principal fue ingreso hospitalario y mortalidad por COVID-19 Analisis estadistico: bivariante seguida de modelos de regresion logistica binaria (Vd : mortalidad/ingreso hospitalario) RESULTADOS: Se incluyeron 156 pacientes con COVID-19, 78 con EIR y 78 sin EIR Los pacientes con EIR no presentaron caracteristicas de la enfermedad COVID-19 diferentes a la poblacion general, tampoco mayor ingreso hospitalario ni mortalidad El factor asociado con mortalidad en los pacientes con EIR fue edad (OR [IC 95%], 1,1 [1,0-1,2];p=0,025), mientras que los factores asociados a ingreso hospitalario fueron edad (OR [IC 95%], 1,1 [1,1-1,2];p=0,007) e hipertension arterial (OR [IC 95%], 3,9 [1,5-6,7];p=0,003) CONCLUSION: La mortalidad y el ingreso hospitalario por COVID-19 no parecen aumentados en las EIR La edad se asocio con mortalidad en EIR y, ademas, la hipertension arterial se asocio con ingreso hospitalario ABSTRACT OBJECTIVE: To describe whether rheumatic inflammatory diseases (RID) are associated with a higher risk of hospitalization and / or mortality from COVID-19 and identify the factors associated with hospitalization and mortality in RID and COVID-19 in different Hospitals in Andalusia METHODS: Design: Multicentre observational case-control study Patients: RID and COVID-19 from different centres in Andalusia Controls: patients without RIS matched by sex, age and CRP-COVID Protocol: a list of patients with PCR for COVID-19 was requested from the microbiology service from March 14 to April 14, 2020 The patients who had RID were identified and then consecutively a paired control for each case Variables: The main outcome variable was hospital admission and mortality from COVID-19 Statistical analysis: bivariate followed by binary logistic regression models (DV: mortality / hospital admission) RESULTS: One hundred and fifty-six patients were included, 78 with RID and COVID-19 and 78 without RID with COVID-19 The patients did not present characteristics of COVID-19 disease different from the general population, nor did they present higher hospital admission or mortality The factor associated with mortality in patients with RID was advanced age (OR [95% CI], 1 1 [1 0-1 2];p = 025), while the factors associated with hospitalization were advanced age (OR [95% CI], 1 1 [1 0-1 1];p = 007) and hypertension (OR [95% CI], 3 9 [1 5-6 7] ;p = 003) CONCLUSION: Mortality and hospital admission due to COVID-19 do not seem to increase in RID Advanced age was associated with mortality in RID and, in addition, HTN was associated with hospital admission

ObjectivesTo describe the prevalence of insulin resistance (IR) in patients with established rheumatoid arthritis (RA) and to analyse the contribution of cumulative inflammatory burden and other factors to its development.DesignObservational cross-sectional study.ParticipantsPatients with RA and controls matched for age, sex and Body Mass Index. We excluded patients with diabetes.SettingsPatients from an RA inception cohort at Hospital Regional Universitario de Málaga, Spain, were recruited between September 2016 and May 2018.Primary and secondary outcome measuresIR was evaluated using the homeostasis model assessment for IR and beta-cell function and the quantitative insulin sensitivity check index. Other variables included the cumulative 28-Joint Disease Activity Score (DAS28) with C reactive protein (CRP) body composition and cytokines. Two logistic regression models were constructed to identify factors associated with IR in patients with RA.ResultsEighty-nine patients with RA and 80 controls were included. The prevalence of IR was similar in both cases and controls. Inflammatory activity was controlled appropriately in patients during follow-up (mean DAS28 3.1 (0.8)). The presence of IR in patients with RA was associated with obesity (OR 6.01, 95% CI 1.9 to 8.7), higher cumulative DAS28-CRP values during follow-up (OR 2.8, 95% CI 1.3 to 6.0), and higher interleukin-1β levels (OR 1.6, 95% CI 1.1 to 2.4). The second model showed that the risk of IR increased by 10% for each kilogram of excess body fat.ConclusionIn patients with well-controlled, established RA, IR is associated mainly with poorer control of inflammation from diagnosis and with obesity, specifically total fat mass.

Objective The aim of the present study was to describe the demographic, clinical and immunological characteristics of patients with late-onset (≥50 years) SLE vs patients with early-onset SLE ( Methods We performed a cross-sectional retrospective study of 3619 patients from the RELESSER database (National Register of Patients with Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). Results A total of 565 patients (15.6%) were classified as late-onset SLE and 3054 (84.4%) as early-onset SLE. The male-to-female ratio was 5:1. Mean (s.d.) age at diagnosis in the late-onset group was 57.4 (10.4) years. At diagnosis, patients with late-onset SLE had more comorbid conditions than patients with early-onset SLE; the most frequent was cardiovascular disease (P Conclusion Late-onset SLE is insidious, with unusual clinical manifestations that can lead to diagnostic errors. Clinical course is generally indolent. Compared with early-onset disease, activity is generally reduced and immunosuppressants are less commonly used. Long-term prospective studies are necessary to determine whether the causes of death are associated with clinical course or with age-associated comorbidities in this population.

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.

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.

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: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: 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.

Rheumatoid arthritis; Multi-omics association analysis; Anti-TNF therapy Artritis reumatoide; Anàlisi d'associacions multi-òmiques; Teràpia anti-TNF Artritis reumatoide; Análisis de asociaciones multi-ómicas; Terapia anti-TNF Background: Rheumatoid arthritis (RA) is the most frequent autoimmune disease involving the joints. Although anti-TNF therapies have proven effective in the management of RA, approximately one third of patients do not show a significant clinical response. The objective of this study was to identify new genetic variation associated with the clinical response to anti-TNF therapy in RA. Methods: We performed a sequential multi-omic analysis integrating different sources of molecular information. First, we extracted the RNA from synovial biopsies of 11 RA patients starting anti-TNF therapy to identify gene coexpression modules (GCMs) in the RA synovium. Second, we analyzed the transcriptomic association between each GCM and the clinical response to anti-TNF therapy. The clinical response was determined at week 14 using the EULAR criteria. Third, we analyzed the association between the GCMs and anti-TNF response at the genetic level. For this objective, we used genome-wide data from a cohort of 348 anti-TNF treated patients from Spain. The GCMs that were significantly associated with the anti-TNF response were then tested for validation in an independent cohort of 2,706 anti-TNF treated patients. Finally, the functional implication of the validated GCMs was evaluated via pathway and cell type epigenetic enrichment analyses. Results: A total of 149 GCMs were identified in the RA synovium. From these, 13 GCMs were found to be significantly associated with anti-TNF response (P < 0.05). At the genetic level, we detected two of the 13 GCMs to be significantly associated with the response to adalimumab (P = 0.0015) and infliximab (P = 0.021) in the Spain cohort. Using the independent cohort of RA patients, we replicated the association of the GCM associated with the response to adalimumab (P = 0.0019). The validated module was found to be significantly enriched for genes involved in the nucleotide metabolism (P = 2.41e-5) and epigenetic marks from immune cells, including CD4+ regulatory T cells (P = 0.041). Conclusions: These findings show the existence of a drug-specific genetic basis for anti-TNF response, thereby supporting treatment stratification in the search for response biomarkers in RA. The present study was funded by the Spanish Ministry of Economy and Competitiveness (Grant Nos. PSE-010000-2006-6 and IPT-010000-2010-36) and by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, FI-DGR 2016, Grant No. 00587), which is supported by the Secretaria d'Universitats i Recerca (Economy and Knowledge Department, Generalitat de Catalunya), and co-funded by the European Social Fund. The study sponsor had no role in the collection, analysis, or interpretation of the data.

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