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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

Background Rheumatoid arthritis (RA) may associate with Interstitial Lung Disease (ILD). Disease-modifying anti-rheumatic drug (DMARD) or TNF alfa inhibitors (iTNF), had been involved in the ILD development as well as exacerbation of an existing one. Nowadays there is no consensus related to treatment. Objectives The aimed of this study is to evaluate efficacy and safety of Abatacept (ABA) treatment in patients with AR and ILD. Methods Multicentre study in patients with RA and ILD associated were treated with ABA. ILD was diagnosed by High Resolution Computed Tomography (HRCT). ABA was used at dose of 10 mg/kg/4 weeks iv or 125 mg/week sc. Its efficacy was evaluated according to the following measures: a) Dyspnea classified by the Modified Medical Research Council (MMRC); Significant variability of 1 point and asymptomatic MMRC=0; b) Pulmonary function test (PFT); Significant oscillations >10% in Forced Vital Capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) >10%; c) Imaging technique (HRCT); d) Joint assessment (DAS28). Quantitative variables were expressed as mean ± SD or as median (interquartile range) and compared with (Wilcoxon test) (Test Fisher) between the baseline and 3, 6 and 12 months. Results 34 individuals were included (19 women /15 men), patients with ILD associated to RA, with a mean age of 61,4 ± 9,8 years. The median duration of RA before ADA was initiated was 4,8 [0,86–13,12] (0–25) years, and had previously received an average 1,29±0,90 DMARDs. RA was seropositive in 24 cases (71%). ILD was associated with a DMARD: MTX (n=3), Etanercept (n=3), Adalimumab (n=3) y Certolizumab (n=1). ABA was used in monotherapy in 14 patients and combined with other immunosuppressors in 20 patients: Leflunomide (LFD) (n=7), LFD and cyclosporine (n=1), Sulfasalazine (n=1), MTX (n=2), MTX with LFD (n=1), hydroxychloroquine (n=5), Hydroxychloroquine with LFD (n=2), Azathioprine (n=1). A significant improvement of dyspnea was observed; patients who didn9t have dyspnea, kept asymptomatic. FVC and HRCT showed a significant improvement during 6 to 12 months period. DLCO remained stable in the majority of the patients. RA (DAS28) activity also improved. After follow up of 12,82±7,48 months, the most significant adverse effects were: pulmonary Infection (n=2), urinary infections (n=1), infusion reactions (n=1). ABA was discontinued due to: Serious infections (n=2); join inefficacy (n=2), pulmonary inefficacy (n=1), infusion reaction (n=1). Conclusions ABA seems to be an effective and relatively safe treatment in patients with RA and associated ILD. This data should be verified again in prospective and randomized studies. Disclosure of Interest None declared

Background Inflammatory bowel disease, either clinical or subclinical is a cardinal pathological process that is central to the spondyloarthropathy (SpA) category of disease that also includes psoriasis, psoriatic arthritis, uveitis and ankylosing spondylitis. Objectives To look for novel genes in familial SpA in large multcase families using a whole genome sequencing approach. Methods We used Whole Genome Sequencing to screen SpA family members with different disease manifestations. We screened 5 multicase SpA families (up to 8 members) with different disease manifestations. Results We found a 1.5MB deletion of the KRT77 gene in 3 of 7 families that segregated with SpA phenotype. Given that KRT77 is a barrier protein and given that tagging SNPs from GWAS studies do not cover the region, and given that both IBD and psoriasis are associated with barrier defects, we looked for an association with KRT77 deletion in 1,000 cases of Psoriasis, 1,000 Crohn’s disease (CD) and 1,001 healthy controls. Deletion genotyping was performed using TaqMan RealTime-PCR assays. The deletion genotype frequencies in controls did not deviate from Hardy-Weinberg Equilibrium (p > .1). We found an association between KRT77 deletion and CD risk (p = 0.03) and also a putative association with pustular psoriasis (p Conclusion Given the strong association between SpA and subclinical gut inflammation and barrier defects in IBD these findings suggest that KRT77 heterozygous deletions with dysregulated gut permeability may play a role in IBD and the wider SpA phenotype. Acknowledgement We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaboration Disclosure of Interests Antonio Julia: None declared, Richard Cuthbert: None declared, Anton Glueck: None declared, Javier Gisbert: None declared, Eugeni Domenech: None declared, Maria Lopez Lasanta: None declared, Nuria Palau: None declared, Helena Marzo-Ortega Grant/research support from: Janssen, Novartis and Pfizer, Consultant for: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Speakers bureau: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Dennis McGonagle Consultant for: Lilly, Novartis UCB, Speakers bureau: Lilly, Novartis UCB, Sara Marsal: None declared

Background: Abatacept (CTLA4-Ig) is an approved biological therapy for the treatment of rheumatoid arthritis (RA). Similar to other biological agents, most patients (60%) respond significantly to this therapy. To date, however, the biological mechanisms underlying the lack of efficacy for this drug are unknown. Objectives: The objectives of the present study were to characterize the biological processes underlying the lack of efficacy of abatacept and to evaluate the blood transcriptome as a valid source for drug response prediction. Methods: A total of n=57 patients diagnosed with RA were recruited for this study from 16 rheumatology departments in Spain. All patients were >18 years old and, had >6 months of disease evolution. The primary clinical response to abatacept was defined at week 12 using the EULAR criteria. Good and moderate responders were aggregated into a single response group, and compared to the no response group of patients. Blood RNA was collected from all patients at baseline. From a subgroup of patients (n=31), blood RNA was also obtained at weeks 12, 24 and 48 of treatment with abatacept. Gene expression levels were determined using paired-end RNA-seq (Illumina). Differential gene expression, association to biological processes, longitudinal association analysis and building of the multigenic predictor were performed using the R software and the specialized Bioconductor libraries. The the prediction accuracy was evaluated using the ROC AUC. Results: From the 57 patients treated with abatacept, n=10 (17.5%) were good EULAR responders, n=24 (42%) moderate EULAR responders and n=23 (40.5%) non-responders at week 12 of therapy. Biological process analysis identified two significantly distinct biological profiles between responders and non-responders. In responders, we found an association to pathways associated with the effector phase of T cells (e.g. interleukin-15 and 2 signalling, P Conclusion: The analysis of blood RNA profiles of RA patients has enabled the identification of specific biological processes associated with the lack of response to abatacept. Also, we demonstrate that blood expression profiles can be predictive of the response to the drug at week 12 of therapy. Disclosure of Interests: Antonio Julia: None declared, Maria Lopez Lasanta: None declared, Antonio Gomez: None declared, Raimon Sanmarti Grant/research support from: Research support: Bristol-Myers Squibb, Speakers bureau: Speakers bureau: Bristol-Myers Squibb, Carlos Marras Fernandez Cid: None declared, Jose Manuel Pina Salvador: None declared, Susana Romero-Yuste: None declared, Raul Maria Veiga Cabello: None declared, Pilar Navarro: None declared, Carme Moragues Pastor : None declared, Silvia Martinez Pardo: None declared, Javier de Toro-Santos: None declared, Amalia Sanchez: None declared, Dacia Cerda: None declared, Alejandro Prada: None declared, Alba Erra: None declared, Jordi Monfort Speakers bureau: Bioiberica Procare Health, ANA URRUTICOECHEA-ARANA: None declared, Nuria Palau: None declared, Raquel M Lastra: None declared, Raul Tortosa: None declared, Andrea Pluma Sanjurjo: None declared, Sara Marsal: None declared

Background Rheumatoid Arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Mullerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyze the relationship between fertility in RA women patients and AMH. Objectives The aim of present study is to determine the AMH serum concentrations in a long-standing RA patients and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs. Methods Serum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by ELISA (Gen II Beckman Coulter Inc.) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student’s t-test or Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. P value Results The median age was similar in AR and control groups (37.4±6.23 vs 37.3±6.27 P=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was Conclusion Our study shows that ovarian reserve determined by HAM serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, HAM levels were not affected by disease activity however a significant correlation was observed between HAM and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have be recommended in RA pregnant patients. References [1] Brouwer J, Fleurbaaij R, Hazes JM, Dolhain RJ, Laven JS. Subfertility in rheumatoid arthritis is often unexplained or caused by anovulation. Arthritis Care Res (Hoboken). 2016. [2] Brouwer J, Hazes JM, Laven JS, Dolhain RJ. Fertility in women with rheumatoid arthritis: influence of disease activity and medication. Ann Rheum Dis. 2015;74(10):1836-1841. [3] Brouwer J, Laven JS, Hazes JM, Schipper I, Dolhain RJ. Levels of serum anti-Mullerian hormone, a marker for ovarian reserve, in women with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65(9):1534-1538. [4] Del Junco DJ, Annegers JF, Coulam CB, Luthra HS. The relationship between rheumatoid arthritis and reproductive function. Br J Rheumatol. 1989;28 Suppl 1:33; discussion 42-35. [5] Dewailly D, Andersen CY, Balen A, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update. 2014;20(3):370-385. Disclosure of Interests 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

Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE Anti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25-30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response. METHODS A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy. RESULTS We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P

Aim: The present study was undertaken to replicate the association of candidate genes for anti-TNF response in rheumatoid arthritis. Candidate genes were selected from a recent genome-wide association study on anti-TNF response performed in a population from Denmark. Materials & methods: Genomic DNA was obtained from 315 Spanish rheumatoid arthritis patients having received an anti-TNF agent as their first biological therapy. SNPs from NR2FR2, MAP2K6, CBLN2 and PDE3A–SLCO1C1 candidate loci were genotyped. Results: The PDE3A–SLCO1C1 locus rs3794271 SNP showed a highly significant association with anti-TNF treatment response (p = 1.74 × 10-5). Combining the statistical evidence from the Spanish and Danish rheumatoid arthritis cohorts, the associated rs3794271 SNP reached a genome-wide significance level of association (p = 3.3 × 10-10). Conclusion: The present findings establish the PDE3A–SLCO1C1 locus as a strong genetic marker of anti-TNF therapy response. Original submitted 9 January 2013; Revision submitted 13 March 2013

Background Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that affects synovial joints. Cervical spine damage, due to rheumatoid inflammation, may produces atlantoaxial subluxation that can produce severe neurological symptoms. Early and aggressive treatment with disease-modifying anti-rheumatic drugs (DMARDs) has been shown to prevent cervical spine damage due to RA, but the effect of the biological therapy (BT) in this particular anatomical location, has not been well established. Objectives To analyze the prevalence of the anterior atlantoaxoidal subluxation (AAS) in RA patients receiving biological therapies and to assess possible risk factors. Methods X-Ray of 221 RA patients treated with at least one BT from December 1999 to December 2012 were analyzed. AAS was defined as an anterior atlantoaxoidal distance ≥3mm. All patients diagnosed of AAS prior to BT were excluded from this analysis and X-Ray from the remaining patients were reviewed at two Time points: before (T1) and after initiating the BT (T2). Epidemiological features (i.e. gender, age and age at diagnosis), clinical features (i.e. rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA) and erosions) and previous DMARDs were analyzed. Disease activity was established according to the index DAS28 at T2 radiographic control. The number of BT during the follow-up was also recorded. A survival analysis of AAS was conducted according to two event models, namely (A) interval right-censored analysis [1], and (B) right-censored analysis with mid-point imputation where the time to AAS was approximately the half time between the BT starting date and the AAS positive X-Ray date. Univariate statistical analysis was performed using both the log rank test in models A and B and the Cox9s proportional-hazards in model B. The latter was also used to perform the multivariate statistical analysis. Results 58 (26%) patients were excluded from this analysis due to AAS prior BT. A total number of n=163 (74%) patients were analyzed. Of these, 89.5% were women, 73% had positive RF and 76% ACPA positive. Erosions were detected in 77% of patients. After BT initiation, AAS was observed in n=38 (23%) patients. The mean value of the period after starting BT and AAS diagnosis was 2.7 years. In the univariate analysis (i.e. Cox9s test), it was found that RF positivity ( P -value=8.56e-03), ACPA positivity ( P -value=5.22e-03) and DAS28 ( P -value=3.59e-03) were associated with AAS development. In multivariate analysis only the presence of ACPA ( P -value=8.57e-03) and elevated DAS28 ( P -value=0.034) at the time of the X-Ray were associated with development of AAS. The duration of the disease was not significantly associated with the development of the AAS. Conclusions In our series of RA patients, it has been observed that AAS development was present in a substantial subset of patients in spite of having started biological therapy. The main risk factors for AAS development in these subgroup of patients was the presence of ACPA antibodies and high disease activity measured by DAS28. References Henschel, Volkmar, Christiane HeiB, and Ulrich Mansmann. intcox: Compendium to apply the iterative convex minorant algorithm to interval censored event data. (2009). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5441