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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

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

Objectives To study the variables associated with the severity of insomnia and hypersomnia according to the Oviedo sleep questionnaire (COS) in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Methods Design. Transversal descriptive study. PATIENTS: Patients with follow-up AS or PSA were selected by consecutive sampling in rheumatology units of 4 Spanish cities. Selection criteria: age ≥16 years old) with AE (New York criteria) or PSA (CASPAR criteria) able to understand and willing to carry out the questionnaires. Protocol: they were explained and the patients were given to meet the selection criteria and the informed consent signed a battery of questionnaires; his doctor performed the evaluation of disease activity and recorded comorbidities and current medication. Main outcomes: the 3 dimensions of COS:1 Subjective satisfaction with sleep,2 Insomnia and3 Hyperinsomnia. Other variables: current medication for AE or PsA, comorbidities, use of sleeping drugs and/or CPAP according to the COS questionnaire, disease activity: axial AS (BASDAI) and PSA (DAS28), quality of life related to health (HRQOL) through SF-36, pain perception (Brief Pain Inventory BPI questionnaire), AE (BASDAI) and PSA (DAS28) and fatigue through FACIT, emotional intelligence through TMMS, resilience with the resilience questionnaire, anxiety screening and depression through HADs. Statistical analysis: Descriptive analysis of the main variables. Bivariate using T-Student, Mann Whitney U and χ2 followed by binary logistic regression (RLB) (Vd: Insomnia: value greater than 22 of the insomnia scale). Results 302 patients participated: 152 patients with AE and 149 patients with PA (47.8% women, 48.97±10.26 years) with an average of 8.35±6.8 years of disease. They used 47.8% biological therapy. The most frequent comorbidities were: disc disease 143 (47.5%), visual impairment 60 (19.9%), anxiety 49 (16.3%), obesity 47 (15.6%) and depression 45 (15%).In the bivariate analysis it was observed that patients with AE suffered more insomnia than patients with PSA (57% vs 43%, p=0.029), they took more drugs to sleep (30.3% vs 22.9%, p=0.001) and suffered a higher activity of the disease measured by BASDAI (mean [SD] 4.7 [1.8] vs 3.8 [1.9], p=0.005). In insomnia in PsA, it was not associated with the degree of activity measured by DAS28 but it was associated with depression. In the binary logistic regression analysis (RLB), insomnia was associated with BASDAI and depression. Therefore, patients with greater BASDAI and depression have almost twice the risk of presenting insomnia in patients with spondyloarthropathies. There are no associations of insomnia with the resilience and emotional intelligence with results above the cut, that is, patients with good resilience and emotional intelligence. Conclusions There is an association between insomnia, disease activity and depression in the group of AE, in the case of PSA there is a relationship with depression. Insomnia is a problem related to depression, so education in sleep hygiene in nursing consultation could be of help for insomnia. Disclosure of Interest None declared

Objectives To study the effectiveness of the use of probiotics in the control of inflammatory activity of patients with rheumatoid arthritis and analyse its effect on their metabolic profile. Methods A bibliographic search was carried out in Medline and Embase. The search strategy included the terms MeSH and the free text of ”lactobacillus”, ”bacillus”, ”probiotics” and ”rheumatoid arthritis.” The search strategies were carried out by two authors, which were included according to the type of studies: meta-analysis, systematic reviews and clinical trials, depending on the type of participant: adults with RA who have received probiotics, the main outcome measures: changes in the Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)), as well as each of the parameters that constitute them: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analogue scale of the doctor and the patient (EVA), number of painful joints (NAD) and inflamed (NAI) and functional status by Health Assessment Questionnaire (HAQ) Secondary variables: number of adverse events and parameters of metabolic activity. The quality of the evidence was analysed following the guidelines of the Scottish Network of Intercollegiate Guidelines (SIGN). Results After the selection of 34 articles, 9 articles were finally included. All were randomised, double-blind, placebo-controlled clinical trials (RCTs) with a level of evidence between 1+and 1++and a recommendation grade of A and B. Seven CDs showed improvement in arthritis measurements. In Peltonen et al. observed a high rate of improvement in the experimental group than in the control group (3.1 vs 2, p=0.027). Mandel et al. they described improvement of the EVA in the experimental group (p=0.046). Zamani the al. they described an improvement in DAS28 (−0.3±0.4 versus −0.1±0.4, p=0.01). Vaghef-Mehrabany et al defined this improvement (p Conclusions Treatment with probiotics seems to be effective in controlling the inflammatory activity of rheumatoid arthritis. Disclosure of Interest None declared

Objectives: To study the differences in severity marker and disease activity in patients with RA and ILD and patients with RA without DILD, and to identify factors associated with ILD in RA patients. Methods: Design:Observational case-control study.Patients: consecutive RA-patients (ACR/EULAR 2010 criteria) with ILD (American Thoracic Society) selected from a prospective cohort from Regional Hospital and Virgen Victoria Hospital of Malaga were included. Controls: RA-patients without ILD. Sex-age matched controls were collected from a prospective cohort of Regional Hospital.Protocol: RA Patients are reviewed every six months in general clinic and patients with biological terapy every three months. All patients are reviewed according to a protocol with systematic data collection. The data of patients with RA and ILD are also collected in a database according to a specific protocol for these patients. The day that was reviewed the last time in consultation will be marked as inclusion date. Data will be collected on the date of inclusion and their clinical records.Outcomes: Difference in severity marker in both groups on the date of inclusion (RF, ACPA, erosive arthritis); in disease Activity Score (DAS28-ESR) and Health Assessment Questionnaire (HAQ); description of modifying antirheumatic drugs (DMARDs);Variables: Demographic, clinical-analytical variables: number of tender joints (TJ), number of swollen joints (SJ), CRP, ESR, general evaluation,DAS28-ESR, HAQ and adverse effects (description, severity and number).Statistical analysis: Descriptive and paired T-test or Chi-square test followed by binary logistic regression (RLB) (Vd:ILD in patients with RA). Results: Fifty-three patients were included, 29 RA with ILD and 24 RA controls. The differences between clinical and epidemiological characteristcs to cases and controls are shown in table 1. RA patients with ILD showed more months with RA duration (p=0.002), more number of exsmokers (p=0.003), erosive arthritis (p=0.011) and ACPA positive (P=0.008). No significant differences in the mean of DAS28 in cases and controls were observed (2.61 vs 2.68; p=0.789), but RA patients with ILD presented worse in physical function parameters by HAQ (1.12 VS 0.63; P=0.032). All patients were treated with disease modifying antirheumatic drugs (DMARDs). RA patients with ILD had: 5 (17.2%) monotherapy with bDMARDs, 17 (58.62) monotherapy with sDMARD and 7 (24.1) sDMARDs with a bDMARDs. In multivariate analysis, the independent variables that were associated with ILD in RA patients were: ACPA elevated (OR [IC95%] =5.0 [1.2–9.9]; p=0.023) and RA duration (months) (OR [IC95%]=1.1 [1.0–1,2]; p=0.037). This model would explain 28% of the variability of the ILD in RA (R2=0.28). Conclusions: The evolution time of arthritis and the presence of ACPA to high titres (>340) were the predictors of ILD in patients with RA in our study. More prospective studies with a greater number of patients are necessary to identify the possible association. Disclosure of Interest: None declared

Background Rheumatoid arthritis (RA) is a long-lasting inflammatory autoimmune disorder that ultimately leads to the destruction of joint architecture. The activity of this disease is measured by the assessment of clinical symptoms. Objectives To apply a proteomic strategy to find serum biomarkers able to discriminate patients with different RA activities. Methods To facilitate the complex measurement of serum by proteomics, a simple, fast and reproducible albumin-specific depletion method using ethanol was optimised and applied to the samples employed in this study. 80 samples from the IMID consortium, classified according to the DAS28 score into low activity40 and high activity40 were analysed by mass spectrometry. Four independent pools of the high RA activity samples (10 samples per pool) and 4 pools of the low RA activity samples were firstly albumin-depleted, and then the remnant serum proteins were digested and differentially labelled with iTraq 8-plex reagents. Subsequently, the 8 labelled pools were combined and cleaned using StageTips-C18. Finally, the pool mixture was fractionated by HPLC (Zorbax-C18) and the resulting fractions were analysed by nanoLC-MS/MS using MALDI-TOF/TOF, TripleTOF and LTQ-Orbitrap. Results The mass spectrometry analysis led to the identification of 186 proteins. In this screening step, the abundance of 9 proteins was found to be significantly different between patients with high (H) and low (L) RA activity. Orthogonal experiments, using Western Blot, protein bead arrays and Multiple Reaction Monitoring (MRM) with synthetic heavy-labelled peptides, were conducted in order to verify some of these these biomarker candidates of RA activity. The results obtained from the verification phase, conducted by MRM on 50 samples from the same cohort, show a decrease of Apolipoprotein B (ratio H/L=0.84, p=0.00), Histidine Rich Glycoprotein (ratio H/L=0.86, p=0.01) and Plasma protease C1 inhibitor (ratio H/L=0.84, p=0.02). Furthermore, this verification phase shows also an increase of Haptoglobin (ratio H/L=1.34, p=0.01) and Serum Amyloid A1 (ratio H/L=1.64, p=0.05), in accordance with that observed in the screening. These proteins are related with the RA process and the effects caused by this type of disease (inflammation and immune disorder in joints). Conclusions In this proteomic study, 5 proteins were found to be quantitatively altered between patients with high and low RA activity using shotgun and targeted mass spectrometry. Disclosure of Interest None declared

Background Tumour Necrosis Factor (TNF) inhibitors have improved the management of many patients with rheumatoid arthritis (RA). However,~30% of anti-TNF treated patients do not show a significant clinical improvement. To date, little is known on the biological mechanisms underlying the differential response to anti-TNF agents. Objectives We sought to identify genetic variation associated with the anti-TNF response in RA using a sequential multi-omics approach. Methods First, we aimed to identify gene coexpression modules (GCMs) associated with anti-TNF response. For this objective, we extracted the RNA from synovial biopsies of 13 RA patients starting anti-TNF therapy and determined the expression profiles using Illumina microarrays. GCMs were identified using the WGCNA approach. The association between GCMs and anti-TNF response was performed using the eigengene of each GCM. Clinical response was defined using the EULAR criteria at week 14. To analyse the association of GCMs with anti-TNF response at the genetic level, we used 348 anti-TNF treated RA patients from Spain. The statistical analysis was performed using GWAS data and the set-based test in PLINK. The GCMs that were significantly associated with anti-TNF response were subsequently tested for validation in an independent cohort of 2706 anti-TNF treated RA patients. The functional implication of the validated GCMs was studied via pathway and cell type epigenetic enrichment analyses. Results We identified 148 GCMs in the RA synovium. From these, 15 GCMs were found to be associated with anti-TNF response (p Conclusions Our study shows the existence of a drug-specific genetic basis for the anti-TNF response. Therefore, this molecular diversity should be considered for biomarker research in RA. Disclosure of Interest None declared

Objectives To describe prospectively the evolution of interstitial lung disease (ILD) in RA treated with modifying antirheumatic drugs (DMARDs) in clinical practice. Methods Design: Multicenter prospective observational cohort. Patients: Patients with RA (ACR/ EULAR 2010 criteria) and ILD (American Thoracic Society) from different centres of Malaga, Valme Hospital of Sevilla and Virgen Nieves of Granada were included. Protocol: All patients with RA and ILD who visited clinic from 2015 to 2017 were recruited. They were reviewed according to a predetermined protocol for data collection. Resolution Computed Tomography (HRCT), Pulmonary function test (PFT) and echocardiogram were requested for all patients who did not have it in the last year. This visit was marked as v0 (index date). At 12 months (v12) the joint assessment (DAS28), echocardiogram, PTF and HRCT were again evaluated. HRCT’s were assessed by the same radiologist. Outcomes: At v12:( 1 improvement (ie improvement in FVC ≥10% or DLCO ≥15% and no radiological progression), 2 non-progression (stabilisation or improvement in FVC ≤10% or DLCO 3 progression (worsening of FVC >10% or DLCO >15% and radiological progression), or 4 death due to ILD. Variables: Description of ILD type and lung function by PTF, HRCT. Presence of PTH by echocardiogram and dyspnoea. Disease activity by DAS28-ESR;Adverse events during the follow-up period. Statistical analysis:Descriptive analysis and Wilcoxon or T test between the v0 and v12. One factor ANOVA between sDMARD, bDMARD and combination therapy groups. Results The main characteristics at V0 of the patients (n=41) are shown in the table 1. Nine patients (21.9%) received a sDMARDs with a bDMARDs;25 patients (60.9%) monotherapy with sDMARD and 7 (17.0%) monotherapy with bDMARDs (table 1). Nine patients (21.9%) had improvement (2 with MTX, 1 with MTX +HCQ, 2 with RTX, 2 HCQ +RTX, 1 MMF +RTX and 1 with ABA); 24 patients (58.5%) remained stable (6 with MTX, 6 with LFN, 3 with HCQ, 1 AZA, 1 SSZ, 1 MMF, 1 TCZ, 2 ABA, 1 MTX +ETN, 1 HCQ +RTX, 1 HCQ +ADA, 1 RTX +MMF); and 7 (17.0%) got worse of ILD (2 with MTX developed lung nodules not known, 2 with LFN, 1 with LFN +IFX, 1 with ETN +MTX and 1 with SSZ). One patient died due to respiratory infection (with RTX). Two patients developed PPH. We did not find significant differences between Vo DAS28 and v12 (2.61 [0.74] vs 2.54 [1.12];p=0.684) or in HAQ (1.12 [0.89] vs 1.23 [0.73],p=0.368). There were no significant differences in PTF, HRCT or DAS28 between sDMARD, bDMARD and combination therapy groups. During the follow-up period 27 patients had infections, the majority (53.7%) respiratory infection. Conclusions Most patients with RA and ILD who are receiving treatment with DMARD (80.5%) remained stable or improved after at least one year of both synthetic and biological DMARD treatment. More prospective studies are necessary to identify the influence of DMARDs in this evolution. Disclosure of Interest None declared

Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with systemic inflammatory processes. Chronic inflammation alters the of the number and type of non-cellular elements, including lipoproteins and glycoproteins. Objectives Here we investigate the plasmatic lipoprotein and glycoprotein profiles associated with SLE. Methods Plasma samples were obtained from 50 healthy control individuals and 50 SLE patients. All patients fulfilled the ACR criteria for classification of SLE. 1H-NMR was used to determine the lipoprotein and glycoprotein profiles from cases and controls. For the lipoprotein profiles, VLDL, LDL, IDL and HDL concentration, lipid composition and particle properties were quantified. The glycoprotein profile was decomposed in four reproducible peak regions LMW, Glyc-B, Glyc-A, Glyc-Lipid and baseline, and quantified for concentration, position and aggregation state. Association analysis to disease was performed using logistic regression fitting for age, gender and body mass index. Classifiers were built using recursive-partition algorithm and classification accuracy was evaluated using receiver operating curves. Results We found a significant perturbation of the lipoprotein profile in SLE patients compared to controls. A statistically significant (P Conclusions SLE is characterized by perturbations of the plasmatic lipoprotein and glycoprotein profiles. The increase of triglyceride VLDL in patients compared to controls, could explain the increased risk for cardiovascular disease observed in SLE. Our results also show that SLE patients have a significantly different glycoprotein profile compared to controls. In both cases, plasmatic 1H-NMR profiling could be a valuable source of informative biomarkers for SLE. Disclosure of Interest None declared

Objectives To investigate the primary respiratory manifestations (PRM) in SLE. Methods All patients in the RELESSER cohort were retrospectively investigated for the presence of PRM Results At least one PRM was present in 11.3% (365/3215) of cases. The most common was pleurisy, occurring in 21.1% of patients, followed by ALP in 3.6%, PE in 2.9%, PPH 4%, DILD in 2%, DAH in 0.8%, and SLS in 0.8%. The variables associated with the presence of PPM are shown in the following table 1: Conclusions PPM independently contributed to a decreased survival in SLE Disclosure of Interest None declared

Objectives To asses insulin resistance (IR) in patients with rheumatoid arthritis (RA) and compare it with healthy controls and to analyse 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 centre 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 >2.29μU*mmol/ml). Secondary outcome: RI measured by quantitative insulin sensitivity check index (QUICKI) ( Results One hundred and fifty six subjects were studied, 4 of them were excluded after OGTT(2 diabetics and their respective controls). Finally, 1522 subjectswer included; 89 RA and 63 controls. The mean age of patients with RA was 56.6 (10.9%)years. Most of them were women(76.4%), with seropositive(FR 83.1% y ACPA 79.1%) and erosive (62%) RA. The mean duration of the disease was 86 (±23)months and mean DAS28 index at the cut-off date of 2.8 (±1.1). 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 28.7% of patients with RA had IR. Of the 25 patients with IR, 75% had an average of DAS28 ≥3.2. In multivariate analysis, the independent variables associated with IR in patients with RA were: Obesity(β=1.7494[p=0.003]), diagnosis delay (β=0.034 [p=0.003]) and disease activity (β=1.045[p=0.058]). This model would explain 23% of the variability of the IR (R2=0.23). Conclusions 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, diagnostic delay and inflammatory activity (measured by mean DAS28 index since the onset of the disease), were the predictors of IR in patients with RA in our study References [1] Clin Rheumatol2016;35(1):43–53. [2] Review. Front Immunol2017;8:1745. [3] Rev Bras Reumatol Engl Ed2017;57(4):320–329. [4] Biomed Res Int2017:9670434. Disclosure of Interest S. Manrique-Arija Grant/research support from: Rheumatology Spanish Society, N. Mena-Vazquez: None declared, I. Urena-Garnica: None declared, S. Abad-Sanchez: None declared, L. Ginel: None declared, C. Fuego-Varela: None declared, M. Rojas-Gimenez: None declared, L. Cano-Garcia: None declared, F. Jimenez-Nunez: None declared, G. Diaz-Cordoves: None declared, M. Ordonez-Canizares: None declared, C. Romero-Barco: None declared, R. Caparros: None declared, M. Irigoyen: None declared, A. Fernandez-Nebro: None declared

Background Recent genome-wide association studies (GWAS) have identified more than 50 loci associated with systemic lupus erythematosus but they explain less than 30% of the heritability of the disease. Meta-analysis including new populations can contribute to identify additional genetic risk factors. Objectives The aim of the presents study was to identify additional genetic risk loci for SLE. Methods We performed a meta-analysis using data from a recent large scale GWAS from 4,036 cases and 6,959 controls from Caucasian European ancestry [1] and a newly genotyped cohort of 907 SLE patients and 1,524healthy controls from Spain. Genetic association was tested at the single-marker level using linear regression and at the pathway-level using Fisher9s modified method. Results Combining the two cohorts we identified genome-wide significant association (P Conclusions In conclusion, we have identified five new risk loci for SLE through a meta-analysis including a new GWAS. References Bentham J, Morris DL et al. Nature Genetics 2015. Acknowledgements We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaboration. We would also like to thank the international SLE consortium for access to the data. Disclosure of Interest None declared

Background PsA has a higher heritability than PsV, indicating the existence of additional PsA-specific genetic factors. To date, however, the specific genetic basis underlying PsA is poorly understood. Objectives The objective the present study was to identify new genetic variation specifically associated with PsA risk. Methods In order to characterize the genetic basis of PsA, we performed a GWAS meta-analysis at the single-marker level as well as at the pathway level (GWPA). A cohort of 835 PsA patients and 1,558 controls from the Spanish population was genotyped for >550,000 SNPs. GWAS data from a second cohort of 1,430 PsA patients and 1,417 controls from the North American population was also used. In order to confirm the specificity of the new genetic variation associated with PsA risk, we analyzed the association with purely cutaneous psoriasis (PsC, n=614) and rheumatoid arthritis (RA, n=1,191). We performed a pharmacogenetic analysis to investigate the new PsA-specific pathways as a source for drug discovery in PsA. Results GWAS meta-analysis identified a new association between B3GNT2 gene and PsA (P Conclusions The present study represents an important step towards the characterization of the genetic factors specific to PsA risk. Disclosure of Interest None declared

Objectives To describe the evolution of interstitial lung disease (ILD) in RA patients treated with disease modifying antirheumatic drugs (DMARDs) for 1 year in real clinical practice conditions. Methods Design: Prospective observational case-series. Patients: Patients with RA (ACR/EULAR 2010 criteria) and ILD (American Thoracic Society/European Respiratory criteria) from two centres (Regional Hospital of Malaga and Valme Hospital of Sevilla) were included. Protocol: All patients with RA and ILD who visited outpatient clinic from January to December 2015. They were reviewed according to a predetermined protocol for systematic data collection. Resolution Computed Tomography (HRCT),Pulmonary function test (PFT) and echocardiogram were requested for all patients.This visit was marked as v0 (index date). At 12 months (v12) the joint assessment (DAS28), echocardiogram, PTF and HRCT were again evaluated. HRCT9s were assessed by the same radiologist with expertise in chest radiology. Outcomes: At v12:(1)improvement (ie improvement in FVC≥10% or DLCO≥15% and no radiological progression),(2)non-progression (stabilization or improvement in FVC≤10% or DLCO 10% or DLCO>15% and radiological progression), or (4) death due to ILD. Variables: Description of ILD type (Nonspecific interstitial pneumonia/Usual interstitial pneumonia) and lung function by PTF, HRCT.Presence of PTH by echocardiogram and dyspnoea.Collection of adverse events. Statistical analysis: Descriptive analysis and Wilcoxon or T test between the v0 and v12. One factor ANOVA between sDMARD,bDMARD and combination therapy groups. Results The main characteristics at V0 of the patients (n=22) are shown in the table. Seven patients (31.8%) received a sDMARDs with a bDMARDs; 12 patients (54.5%) in monotherapy with sDMARD, with MTX being the most frequent (34.7%); 3 (13.6%) in monotherapy with bDMARDs (Table 1). Three patients (13.6%) had improvement (1 with MTX, 1 with RTX and 1 with HCX + RTX), 15 patients (68.2%) remained stable (4 with MTX, 3 with LFN, 1 with HCQ, 1 AZA, 1 ABT, 1ABT + SSZ, 2 MTX + ETN, 1 HCQ + RTX, and 1 HCQ + ADA);and 3 (13.0%) got worse of ILD (1 with MTX developed unknown lung mass, 1 with LFN and 1 with LFN + IFX). One patient died during follow-up due to respiratory infection (under treatment with RTX). No patient developed PPH. We did not find significant differences between v0 DAS28 and at 12 months (2.55 [0.75] vs 2.42 [1.22], p=0.567) or in HAQ 1.15 [0.93] vs 1.25 [0.78], p=0.450). There were no significant differences in PTF, HRCT or DAS28 at v12 between sDMARD, bDMARD and combination therapy groups. Four patients (18.2%) had adverse effects: 2 respiratory infections, 1 oral herpes simplex and 1 tooth infection. Conclusions Most patients with RA and ILD who are receiving treatment with DMARD (82%)remained stable or improved after at least 1 year of both synthetic and biological DMARD treatment. However, a significant percentage of patients had an adverse outcome. More prospective studies with a greater number of patients are necessary to identify the influence of DMARDs in this evolution. Disclosure of Interest None declared

Objectives To describe 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: Observational 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. All participants signed informed consent. 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 Sixty-two subjects were studied, 8 of them were excluded after OGTT (4 diabetic patients and their respective controls). Finally, 54 subjects were included; 27 RA and 27 healthy controls. The mean age of patients with RA was 52.2 (12.1) years. Most of them were women (88.9%), with seropositive (FR 81.5% and ACPA 74.1%) and erosive (63%) RA. The mean duration of the disease was 85.6 months (27.1) and mean DAS 28 index since the onset of the disease of 2.98 (0.9). 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 subjects with IR in cases and controls were observed. 33.3% of patients with RA had IR. In multivariate analysis, the only independent variable associated with IR in RA patients was disease activity score (DAS28) (OR [95% CI] = 3.6 [1.0–12.9], p=0.045). Conclusions The only predictor of IR in RA patients was the inflammatory activity measured by DAS28. We did not find a higher IR in RA patients than in healthy controls, it could be because the patients were well treated and the inflammatory activity was controlled in the most of them. Disclosure of Interest None declared

Background There is limited evidence on the risk of neoplasia in autoimmune diseases such as systemic lupus erythematosus. Objectives The objective of this study is to analyze the incidence of cancer in the Spanish population with SLE and the factors associated in its development: RelesSER Registry Data. Methods We calculated the incidence density of malignant neoplasms, the standardized incidence ratio and the average time to develop the first neoplasm after diagnosis of SLE in patients of the SLE registry of the Spanish Rheumatology Society (RelesSER) fulfilling ACR97 criteria. We carried out a bivariate analysis of the associated factors to neoplasms and multivariate by logistic regression. Results A total of 3607 patients (90.4% female) were included. We registered 140 neoplasms in women (4.3%) and 14 in men (4%) (p 65 years was 0.98; 0.59 in men and 1.55 in women. The average time until de development of the first malignant neoplasm was 10 years (RI:5.75–17.00), being lower in women [9.5 (RI: 5.00–17.0) years] than in men [12.5 (8.75–17.5)] and in patients under 45 years versus over 45 years [8.0 (RI: 5.00–16.00)]. Malignant neoplasms were the cause of death in 10% of the patients (15/154), predominantly hematological and breast cancers, both at 19% followed by lung cancer in 14.3%. Factors associated to malignant neoplasms in the bivariate analysis are shown in (table 1). No immunosuppressive therapy was associated with the development of neoplasms. In the multivariate model, adjusted for age and time of disease duration, age was the only significant variable (OR:1.030; 95% CI: 1.003–1.059; p=0.029) with a trend for ACE inhibitors use (OR:1.866; 95% CI: 0.808–4.306; p=0.144), SLEDAI (last visit) (OR: 0.904; 95% CI: 0.806–1.015; p=0.089, SLICC/ACR DI) (without neoplasias) (OR: 1.160; 95% CI: 0.961- 1.401; p=0.123), and duration of the disease in months (OR: 1.003; 95% CI: 1.000–1.006; p=0.068). Conclusions The incidence of neoplasia in Spanish women with SLE is higher than expected for age and gender. Malignant neoplasms were the cause of death in 10% of the patients, predominating hematological and breast cancers followed by lung cancer. Acknowledgements The RelesSER registry has been supported by the FIS (ISCIII) - European Regional Development Fund (FEDER), fellowship PI11/02857. It has also been partially funded by: GSK, UCB, Roche and Novartis. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a long-lasting inflammatory autoimmune disorder that ultimately leads to the destruction of joint architecture. Objectives Using the DAS28 activity index, 80 RA serum samples (40 with low activity and 40 with high activity) were selected in order to be analyzed by mass spectrometry. The aim of this study was to find possible protein biomarkers that could discriminate patients with different RA activity in the daily clinical routine. Methods In order to facilitate the complex measurement of these serum samples, a simple, fast and reproducible albumin-specific depletion method using ethanol was optimized and applied to this study. Four independent pools of the 40 high RA activity samples (10 samples per pool) and 4 pools of the 40 low RA activity samples were firstly albumin-depleted, and then the remnant serum proteins were digested and differentially labelled with iTRAQ 8-plex reagents. Subsequently, the 8 labelled pools were combined and cleaned using StageTips-C18. Finally, the pool mixture was fractionated by HPLC (Zorbax-C18) and the resulting fractions were analyzed by nanoLC-MS/MS using two different equipments for validation (MALDI-TOF/TOF and TripleTOF). Results The mass spectrometry analysis led to the identification of 186 proteins. Among these, Haptoglobin, Kininogen-1, Alpha-2-HS-glycoprotein, Serum Amyloid A, Afamin and Histidine-rich-glycoprotein, exhibited a differential relative abundance depending on the RA activity of the patients (p Conclusions In this proteomic study, 9 proteins were found to be modulated between patients with high and low RA activity. Most of these proteins are related with the RA process and the effects caused by this type of disease (inflammation and immune disorder in joints). Therefore, these proteins are possible biomarker candidates for improving RA monitoring. Future validation experiments and prospective studies are needed to facilitate their implementation in the clinical routine. Disclosure of Interest None declared

Background Autoimmune diseases are highly disabling chronic disorders characterized by the activation of multiple immune and inflammatory pathways against self-components. Clinical studies have demonstrated that autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. Understanding the genetic and biological mechanisms underlying cardiovascular disease (CVD) risk in autoimmunity could therefore be fundamental to develop more efficient preventive and therapeutic strategies. Objectives The objective of this study was to characterize the genetic basis of CVD risk in autoimmune diseases. Methods A total of 6,485 patients from the six autoimmune diseases RA, PA, SLE, PS, CD and UC were recruited by the Spanish biomedical consortium IMID Consortium. All patients were Caucasian European from the Spain. CVD patients were defined as having ≥1 out of the 3 most frequent cardiovascular phenotypes: (i) ischemic heart disease (ii) cerebrovascular accident and (iii) peripheral arterial disease. In order to characterize the genetic basis of CVD risk in autoimmune diseases, we used genome-wide genotyping data from all autoimmune disease patients included in the study. First, we tested the association of established CVD risk variants within each autoimmune disease. Second, we analyzed the association of autoimmune disease risk variants with an increase in CVD risk. Finally, we used the cross-phenotype meta-analysis approach (CPMA) to perform a genome-wide meta-analysis and identify global genetic patterns associated with CVD risk in autoimmune diseases. Results A total of 17 loci previously associated with CVD risk in the general population were significantly associated with CVD risk in the autoimmune patient cohorts ( P P CFLAR-CASP8 . The CPMA identified a total of 10 genetic patterns significantly associated with CVD risk across all autoimmune diseases. Two of these patterns showed a highly significant association with CVD risk in RA, PsA and SLE. The functional analysis of these two genetic patterns revealed a significant enrichment in key pathways related to the etiology of rheumatic diseases like TNFα ( FDR (FDR Conclusions The results of the present study represent an important step towards the characterization of the genetic basis of CVD in autoimmune diseases. These findings contribute to explain the higher prevalence of cardiovascular events observed in patients with autoimmune diseases compared to the general population. Disclosure of Interest None declared

Background Adults with rheumatoid arthritis have been shown to have a reduction in lean mass and increased adiposity, despite presenting normal Body Mass Index (BMI). Several studies have shown increased adiposity induces a proinflammatory state which lead to a worse response to treatment. There are few publications about this subject in juvenile idiopathic arthritis (JIA) Objectives Describing body composition and anthropometric parameters in JIA patients, and evaluating relationship between adiposity and inflammatory in these children. Methods Observational cross-sectional study, in JIA patients from 4 to 15 years, monitored by a Pediatric Rheumatology Unit. Monoarticular forms were excluded. Anthropometric, clinical and treatment data were recorded. DXA (measuring bone and fat mass) were obtained. Fat Mass Index (FMI) was defined as fat mass (kg)/height (m2) and fat-free mass index (FFMI) as lean mass (kg)/height (m2). JADAS27 index was used to evaluate inflammatoty activity. Results We analyzed 80 patients, whose characteristics are shown in table 1. The most frequent JIA subtype was oligoarticular (16.3% extended,47.5% persistent) followed by polyarticular (25.1%). Twenty five percent of patients had uveitis. Fifty percent them had inactive disease with treatment, 26% had activity and 23% were inactive without treatment. Regarding the treatment, 52.5% were on methotrexate and 30% on a biological drug (22.5% antiTNFα, 5% antiIL-1, 2.5% antiIL-6). Disease duration average was 6.6 years (± 3.7SD). JADAS27 index mean score was 2 (±4SD), CRP 4.7mg/l (±9,5SD), ESR 8.7mm (±7,2SD) and CHAQ 0.17 (± 0,38SD). Anthropometric parameters are shown in table 1. Mean JADAS27 index score in patients with normal BMIwas lower (1.7±3.6 SD) than mean JADAS27 index score in overweight and obese patients (3.3±6.0SD), although this difference was not significantly (p=0.255). In multiple linear regression, an increase of 0.3 JADAS27 was observed for each unit of FMI increase (p=0.03). This relationship was maintained in the multivariate analysis (B0.015; p0.01) independently of JIA subtype and received treatment. Conclusions In JIA patients, there is a linear relationship between FMI and disease activity measured by JADAS27, but most patients had a normal BMI. The establishment of this relationship (fat-inflammatory activity) would be transcendental due to the need to optimize the recommendations in the JIA approach. References Alvarez-Nemecye J, Buenfil-Rello FA, Pacheco Pantoja El. Association between body composition and disease activity in rheumatoid arthritis. A sistematic review. Reumatol Clin. 2016;12(4):190–5. Disclosure of Interest None declared

Background 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 SSc patients. However, the genetic factors involved in lung complication are not well-defined. Objectives We aimed to revisit 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, besides testing the association of this polymorphism with SScrelated pulmonary involvement. Methods A total of 4,393SSc patients and 16,591 unaffected controls from six cohorts of European origin were genotyped for the MIF promoter variant rs755622. An inverse variance method was used to meta-analyze the data. Results A statistically significant increase of the MIF rs755622*C allele frequency compared to 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 SSc patients showing both clinical manifestations (dcSSc with PAH: P=6.91E-3, OR=2.05). Conclusions We revisited 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 dSSc patients. Disclosure of Interest None declared

Objectives To study the psychological variables associated with the severity of insomnia and hypersomnia according to the Oviedo sleep questionnaire (COS) in patients with spondylarthritis (SPA) and psoriatic arthritis (PA), including the disease activity BASDAI and DAS28. Methods Design. Cross-sectional descriptive study. Patients: Patients with consecutive SPA or PA were selected by consecutive sampling in follow-up in rheumatology units of 4 Spanish hospitals. Inclusion criteria: Adults (age ≥16 years) with SPA (ASAS criteria) or PA (CASPAR criteria) capable of understanding and willing to perform questionnaires. Exclusion criteria: other rheumatic diseases, age Results A total of 126 patients participated: 65 patients with SPA (33.8% women, 49.92±10.92 years) and 61 patients with PA (60.7% women, 49.4±9.5 years) with an average of 8.4±6.8 years of disease. They used biological therapy SPA 29 (23%) and PA 28 (45.9%). The most common comorbidity were in SPA and PA: disc disease 33 (50.8%) and 18 (29.5%). 16 (24.6%). Both patients with SPA and PA were dissatisfied with their sleep (3.42±1.39). We did not find correlation of the COS variables with the HRQoL, the fatigue or the pain. There were no differences in COS scale according to biological treatment and/or FAME. Logistic regression analysis demonstrated an association between insomnia and TMMS repair, resilience and anxiety in PA. Insomnia in SPA showed an association with depression and BASDAI Conclusions Insomnia is a common health problem in these diseases. Moderate-intense insomnia in patients with SPA was associated with an increase in BASDAI and depression. Also in patients with PA, the insomnia was associated with TMMS repair, resilience and anxiety. The patient assumes the slepp dissorder as part of this chronic illness, this jutifies the good evaluations of resilience and emotional inteligence of the evaluated patients. Disclosure of Interest None declared

Objectives To describe the body composition and physical activity of patients with RA Methods Design: Observational case-control study. Population: 31 consecutive RA-patients (ACR/EULAR 2010 criteria) selected from a prospective inception cohort (diagnosis of RA between 2005 and 2012),and 31 sex and age-matched voluntary controls. Protocol: We included 62 subjects who were assessed using dual-body X-ray absorptiometry (DEXA) for the assessment of body composition at study entry. Data on clinical activity were also collected from the onset of the disease.The level of physical activity was assessed according to the abbreviated protocol of the International Physical Activity Questionnaire (IPAQ). Main outcome: Fat mass index (FMI) and fat free mass index (FFMI).FMI was defined as fat mass (kg)/ height (m 2 ) and FFMI as lean mass (kg)/height (m 2 ). Secondary outcome: description of the anthropometric parameters:BMI (body mass index),waist-hip index. Variables: Demographic, treatment, clinical-analytical variables: Disease Activity Score of 28 joints (DAS28-ESR), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI);Anti–cyclic citrullinated peptide (ACPA), Rheumatoid factor (RF),Health Assessment Questionnaire (HAQ)and erosions.BMI was categorized according to the OMS classification. Waist- hip index (central obesity>1 for men and>0.8 for women). Statistical analysis: Descriptive and paired T-test or ranks test and Wilcoxon signed rank,as required Results We included 62 subjects,31 RA (50%) and 31 controls (50%).The mean duration of the disease of RA patients was 84.4 months. With a DAS28 mean of 3.04 (0.8), mean HAQ of 0.77 (0.6). The majority presented erosions (64.5%) RF (83.9%) and ACPA (77.4%) positive. Differences in clinical and densitometric anthropometric parameters between cases and controls are shown in Table 1. Significant differences were observed in the proportion of overweight subjects between cases and controls (p=0.03). A higher percentage of controls had moderate to high physical activity compared with the patients (65.5% vs 34.8%). The majority of patients with RApatients had low physical activity (74.2%).These had a mean (SD) of HAQ higher than patients with moderate-high physical activity [1.2 (0.9) vs 0.66 (0.6); p=0.09].Finally, patients performing moderate-high physical activity had less inflammatory activity than those performing low physical activity,with a DAS28 mean of 2.69 (0.7) vs 3.08 (0.9) ;p=0.308, respectively Conclusions Patients with RA compared to controls show more overweight and less physical activity Disclosure of Interest None declared

Objectives To analyze the medical ramifications that are made to the consultation of telecare of Rheumatology Nursing (CTCER) of our hospital and health care activity generated by this. Methods Design: Observational study cross. Patients: 301 patients for follow-up were derived to CTCER in a hospital of third level of January - November 2016. Our hospital serves a population of 600,000 people. Protocol: We have a specific document for referral to CTCER where the rheumatologist specifies the reason for referral, the nurse review period and diagnosis. Nurse appointment the patient in its agenda for the telephone follow-up on the date indicated and recorded in the history of the patient efforts made the day of the appointment. The most common medical efforts making the nurse are preset by consensus with rheumatologists. Coming out than expected are reviewed with responsible for the patient9s rheumatologist. Variables analyzed: diagnosis, reason shunt type of FAME, adverse events, appearance of Comorbidities, nurse management, new problems after telephone consultation. Statistical analysis: descriptive analysis of the main variables. Results Of the 301 patients, 68.4% were women. The diagnoses were: rheumatoid arthritis (RA) 116 (38.5%), spondyloarthropathy (SpA) 34 (11.3%), psoriatic arthritis (PsA) 45 (15%), systemic lupus erythematosus (SLE) (18.9%), vasculitis 1 (0.3%), arthritis juvenile idiopathic (AJI) 5 (1.7%), Still9s disease adult 3 (1%), osteoporosis 4 (1.3%), 4 undifferentiated arthritis (1.3%). Them reasons of referral were: control to the month of home of FAME synthetic 120 (39.9%), Control to the home of FAME biological 28 (9.3%), review consultations 110 (36.5%), control toxicity hepatic 17 (5.6%), control alteration hematologic 7 (2.3%), control alteration renal 1 (0.3%), control of security of treatment Mycophenolate 4 (1.3%), control of safety of Teriparatide 6 (2%), wish gestational 1 (0.3%), analytical control not performed in consultation 13 (4.3%) (Table1). The most derived synthetic FAME was methotrexate 174 (57.5%) and the most derived biological FAME was etanercept 16 (5.3%) (table2). Nurse managed bypass autonomously 298 (99%) referrals, need help of the rheumatologist in 2 (0.7%) referrals and having only 1 shunt derived to 2017. 17 (5.6%) leads new problems with the call appeared: intolerance digestive 11 (3.7%), headache 3 (1%), worsening 1 (0.3%), moderate 1 infection (0.3%), poor adhesion 3 (1%), new comorbidity 3 (1%). Conclusions The inquiry of telecare is a form of collaborative work rheumatologist-nurse. The nurse can manage leads independently without having to go to your rheumatologist. This type of nurse call brings improvements in patient care, prevents displacement, decreased on-site visits and improves the safety of patients. Disclosure of Interest None declared