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ObjectivesTo describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19.MethodsAn observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission.ResultsThe study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3–10) days. The median length of stay was 9 (6–14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model.ConclusionOur results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.

We appreciate the interest of Aydin et al 1 in our study about risk factors for hospital admissions related to COVID-19 in patients with inflammatory rheumatic diseases (IRD).2 COVID-19 pandemic is a matter in constant update and certainly an enormous challenge for researchers, clinicians, healthcare workers and epidemiologists. In this sense, all together are making enormous efforts in their fields to overcome this global crisis. In relation to research advances, there has been an explosion in the publication of articles related to COVID-19. In this pandemic situation, it is true that it has been a challenge and a race against the clock for researchers and some publications could be less rigorous than expected.3 For this reason, and according to Aydin et al ,1 the critical reading it is important to interpret the results, paying special attention to the limitations of each study. The role of IRD, their therapies and other potential factors in the risk of SARS-CoV-2 infection and …

Objective: To estimate and compare the observed and expected prevalence of the co-existence of rheumatic diseases (RD) with other chronic conditions. Methods: The self-reported diagnosis of chronic conditions was obtained from the 2192 participants in a national health survey (Spain, 1999–2000) We compared the estimated prevalence of the co-existence of a RD with other chronic conditions, to the expected prevalence using two-sample test of proportion. Results: The observed (O) prevalence was significantly higher than expected (E) in the following combination of self-reported diseases: RD+arterial hypertension (O/E ratio = 1.88), RD+diabetes mellitus (O/E ratio = 2.07), RD+hypercholesterolemia (O/E ratio = 1.87), RD+cardiological (O/E ratio = 1.83), and RD+digestive diseases (O/E ratio = 2.07). The prevalence of selected co-existent pairs of diseases is more frequent with increasing age and differs between women and men. Conclusions: The excess in prevalence of some combinations of diseases may serve as a reminder to the rheumatologists that many of their patients will have co-existent disease of which they need to be aware to properly plan their management. It may also be a sign of common risk factors between diseases or of adverse events.

Recent studies have focused attention on the involvement of NLRP1 to confer susceptibility for extended autoimmune/inflammatory disorders, being considered a common risk factor in autoimmunity.1–3 NLRP1 provides a scaffold for the assembly of the inflammasome that activates caspases 1 and 5, required for processing and activation of the proinflammatory cytokines interleukin 1β (IL-1β), IL-18 and IL-33 and promoting inflammation.4 In this study, we examined for the first time whether NLRP1 is associated with giant cell arteritis (GCA), a chronic systemic vasculitis affecting large and medium-sized arteries derived from the aorta, in particular the cranial branches of the carotid artery. GCA is the most common vasculitis in the elderly in Western countries with a female predominance.5 To investigate the possible genetic association of NLRP1 with this disease, we genotyped a single-nucleotide polymorphism (rs8182352), which has been reported to confer risk to the development of autoimmune processes in previous studies,1 ,2 in a total of 3583 individuals, comprising a discovery set from Spain (574 patients diagnosed with biopsy-proven GCA and 2366 healthy controls) and a replication set of subjects from Italy (111 biopsy-proven GCA patients and 532 controls) using a predesigned TaqMan allele discrimination assay. All individuals were of …

Background Uveitis encompasses a diverse group of inflammatory diseases associated with a significant risk of substantial and sometimes permanent visual loss. Although corticosteroids are the initial treatment, immunosuppressive therapy (IST) may be needed in case of inadequate response and/or side-effects. Most of the data regarding efficacy, tolerability and discontinuation rates of ISD in uveitis patients comes from clinical trials, as data from observational studies in uveitis are scarce. However, it is important to take into account that the trial settings are different from day-to-day clinical practice, which limits the validity of the extrapolated data to patients in daily practice. Objectives To assess the long-term survival of ISTs in uveitis patients in real-life clinical practice. Factors associated with discontinuation were also analyzed. Methods An observational retrospective longitudinal study of uveitis patients taking ISTs from 1989 to 2014 was conducted. The primary endpoint was IST discontinuation due to: clinical improvement, inefficacy, adverse drug reaction (ADRs), and other causes. Incidence rates of discontinuation (IR) per 100 patient-years were estimated. Variables associated with specific causes of discontinuation were analyzed using Cox bivariate and multivariate models. Results We included 225 courses of IST in 95 patients (565.3 patient-years of observation). Cyclosporine [62 patients (65.3%)], methotrexate [44 (46.3%)], azathioprine [28 (29.5%)], and anti-TNFs [30 (31.6%)] were the most frequently used. Treatment was suspended in 116 cases (IR 20.5 with 95% confidence interval [17.1 to 24.6]). In the first year of therapy 75% continued on IST, and after ten years, the retention rate was 16%. The IRs due to clinical improvement, inefficacy and ADRs were 8.0 [5.9 to 10.7], 5.1 [3.6 to 7.4], and 4.4 [3.0 to 6.5], respectively. The IRs of all cause discontinuation for cyclosporine, methotrexate, azathioprine, and anti-TNFs were 21.7 [16.3 to 28.8], 10.9 [7.3 to 16.3], 18.7 [12.4 to 28.2], and 24.1 [16.0 to 36.2] per 100 patients-year, respectively. In the multivariate analysis, combined therapy was associated with a higher rate of discontinuation, regardless the cause. Presence of vasculitis was associated with a higher rate of discontinuation due to clinical improvement, and presence of macular edema was associated with higher risk of discontinuation due to inefficacy. Conclusions The major causes of IST discontinuation in cohorts of uveitis patients were clinical improvement and inefficacy. Methotrexate showed the lowest rate of discontinuation, while anti-TNFs showed the highest rate. Combine therapy with IST was associated with higher discontinuation rate regardless the cause. Presence of vasculitis and macular edema were associated with a higher risk of discontinuation due to clinical improvement and inefficacy, respectively. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is an autoimmune pathology associated with increased risk of cardiovascular (CV) disease and subclinical atherosclerosis 1 . Consequently, both inflammatory diseases share common molecules involved in its pathogenesis. In this sense, interleukin 17A (IL-17A) is a pro-inflammatory cytokine involved in the regulation of immune responses and chronic inflammation 2 . Objectives To evaluate the potential association between different IL-17A polymorphisms and CV events, as well as subclinical atherosclerosis, in a large cohort of Spanish RA patients. Methods Five IL-17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were genotyped by TaqMan assays in a 7900 HT Real-Time polymerase chain reaction system in 1,974 Spanish patients diagnosed with RA (fulfilling the 2010 American College of Rheumatology classification criteria for RA 3 ), recruited from different Spanish hospitals. 318 patients (16.1%) had experienced CV events, and 822 had undergone carotid ultrasonography studies to assess subclinical atherosclerosis (presence/absence of plaques and carotid intima media thickness [cIMT]). The relationship between IL-17A alleles, genotypes and haplotypes and CV events, presence/absence of plaques and cIMT values was assessed. Results were adjusted for sex, age at diagnosis and traditional CV risk factors. Results No statistically significant differences were observed when allelic/genotypic frequencies of each IL-17A polymorphism were assessed regarding presence/absence of CV events, plaques or cIMT values. This was also the case when the five polymorphisms were combined to form haplotypes. Conclusions Our results do not confirm an association between the five IL-17A polymorphisms studied and the development of CV events or subclinical atherosclerosis in our cohort of Spanish RA patients. References Avina-Zubieta JA et al. Ann Rheum Dis. 2012;71:1524–9. Shabgah AG et al. Postepy Dermatol Alergol. 2014;31(4):256–61. D. Aletaha T et al. Arthritis Rheum. 2010;62:2569–81. Acknowledgement This study was supported by European Union FEDER funds and “Fondo de Investigaciόn Sanitaria” (PI12/00060 and PI15/00525) (Spain), and partially supported by RETICS Programs RD12/0009 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain). FG is a recipient of a Sara Borrell postdoctoral fellowship from the ISCIII (Spain) (CD15/00095). RL-M and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013). Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease. Elevated levels of the C-reactive protein (CRP) are related to an increase risk of coronary artery disease [1] and stroke [2]. Recently, PCR, GCKR, HNF1A, LEPR, ASCL1 and NLRP3 have been associated with CRP levels in non-rheumatic population [2]. Objectives We aimed to determine the potential role of these genes in the development of CV disease and subclinical atherosclerosis in patients with RA. Methods Genotyping was performed in 2,384 Spanish RA patients by TaqMan assays. Subclinical atherosclerosis was determined by carotid ultrasonography (US) in 1,193 patients. Results No statistically significant differences were found when PCR, GCKR, HNF1A, LEPR, ASCL1 and NLRP3 were assessed according to the presence/absence of CV disease. It was also the case when patients were stratified according the presence/absence of subclinical atherosclerosis. Conclusions Our results do not confirm an association between these genes and the development of CV disease and subclinical atherosclerosis in patients with RA. References Danesh et al. N Engl J Med 2004, 350(14):1387–1397; Ridker et al. N Engl J Med 1997, 336(14):973–979; Dehghan A et al. Circulation, 123(7):731–738. Acknowledgement This study was supported by European Union FEDER funds and “Fondo de Investigaciόn Sanitaria” (grants PI12/00060 and PI15/00525) from `Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain), and in part by grants from the European IMI BTCure Program. RL-M and BU is supported by funds from the RETICS Program (RIER) (RD12/0009/0013). FG is a recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD15/00095). Disclosure of Interest None declared

The IL-23R region is associated with a number of non-infectious inflammatory conditions including inflammatory bowel disease, ankylosing spondylitis and psoriasis,1,–,3 and albeit with less consistent evidence, rheumatoid arthritis (RA).4,–,6 Association of rs1343151 (G→A) with RA, but not rs1004819/rs10489629/rs2201841 , has been reported in European and New Zealand sample sets;5 none of rs3212227/rs6887695/rs7530511 was associated in European and North American sample sets,6 and rs7517847 was not associated in meta-analysed European and New Zealand sample sets.4 Given the immunological evidence pointing to the importance of the Th17–IL-23 axis in inflammation and autoimmunity,7 and the unresolved question of whether or not IL-23R is associated with RA, we further investigated association of IL-23R with RA in white European Caucasian case–control sample sets (cases ascertained …

Background Previous trans-ethnic meta-analysis including samples from European and Asian individuals support the hypothesis that the genetic component of rheumatoid arthritis is shared. However, our knowledge about populations such as the native population of Americans, also called Amerindians or Native Americans, is poor. Few genetic studies have been conducted in Amerindian populations. Objectives We conducted a meta-analysis of Latin American, with Amerindian-European (primarily South European) admixed individuals and Spanish, in order to find new risk loci for RA susceptibility shared and specific for each one of them. Methods A total of 5,533 subjects were genotyped with the immunochip custom array and included in the final data set. The OR of the meta-analysis of both populations was performed using the inverse variance method under fixed-effects model. The imputation process of the MHC region was performed with a dense reference panel using the Beagle software. Results We confirm the association in this population at genome-wide significant level of the HLA and PTPN22 . The MCH analysis showed that four amino acids in positions 11, 13, 70 and 86 of the HLA-DRβ1 explain all the association in our combined analysis. Interestingly, we observed differential associations in each cohort separately. In the Spanish cohort, only amino acids 13 and 86 of HLA-DRβ1 were necessary to explain all the association in the MHC region, while for the Latin American population, amino acids at positions 13 and 70 were the important ones. Outside of the HLA region, the most interesting signals observed were on 2p25.3, 3q25.33 and 7p12.2 where the MYTL1 , IL12A and IKZF1 genes are located, respectively. Conclusions Our results show that the comparative use of two populations provides clues on the diversity and the history of the genetic susceptibility behind a complex disease such as RA. References Kim, K. et al. Ann. Rheum. Dis. (2014). doi:10.1136/annrheumdis-2013-204749 Jia, X. et al. PloS One 8, e64683 (2013). Raychaudhuri, S. et al. Nat. Genet. 44, 291–296 (2012). Acknowledgements This work was supported by the followuing grants: Instituto de Salud Carlos III (ISCIII) from Spanish Health Ministry RETICS Program RD12/0009 and PI12/02558, the C2A Andalusian recruitment program from Junta de Andalucia (Spain), the European IMI BTCure Program and the Swedish Research Council. MT is supported by the Instituto de Salud Carlos III (Spanish Health Ministry), through the Sara Borrell subprogram [CD13/00316]. Disclosure of Interest None declared

Background Joint damage is a key pathological feature of Rheumatoid Arthritis (RA) and is characterized by a high level of heterogeneity. There is recent evidence suggesting an association of IL2RA and C5orf3 loci with the degree of joint destruction in RA. Objectives Using a large cohort of RA patients we have performed the validation of this two candidate genes for joint destruction and analyzed in relation to the main disease phenotypes. Methods A total of 857 RA patients were recruited and their level of joint destruction was measured. The previously reported single nucleotide polymorphisms at IL2RA (rs2104286) and C5orf30 (rs26232) loci were genotyped in the patient cohort using Taqman RealTime-PCR. The two loci were tested for association with the level of joint destruction using linear regression. Clinically relevant variables were analyzed independently with the level of joint damage and in relation to the genetic polymorphisms using linear regression analysis. Results We found a highly significant association between IL2RA locus SNP rs2104286 with the level of joint destruction in RA ( P =0.0017). In our cohort, variation at C5orf30 locus did not show any evidence of association. Years of disease duration ( P =2.6e-54), number of previous biological therapies ( P =4.3e-9), body-mass index (BMI, P =6.9e-5), Anti-Citrullinated Peptide Antibodies (ACPA) status ( P =0.0001) and Rheumatoid Factor (RF) status ( P =0.009) were also found to be significantly associated with the level of joint damage in RA. The genetic association between IL2RA locus and bone erosions was found to be restricted to autoantibody-positive (74% ACPA-positive, P =0.001; 74% RF-positive, P =0.004) and female (77%, P =0.01) patients. Conclusions The results of this study confirm the association of IL2RA with joint destruction in RA and suggest that this genetic variation is relevant to a specific patient phenotype. Acknowledgements This work was supported by the Spanish Ministry of Economy and Competitiveness Strategic Project grants [PSE-010000-2006-6, IPT-010000-2010-36] and the Fondo de Investigaciόn Sanitaria grant [11/0551]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Disclosure of Interest None declared

Background Immune mediated and inflammatory diseases (IMIDs) such a rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (Ps), and psoriatic arthritis (PsA), are associated with higher rates of cardiovascular (CV) morbidity and mortality, mostly due to accelerated atherosclerosis. Classic CV risk factors do not fully account for the gap observed in the prevalence and incidence of CV disease, when compared to that of the general population. Objectives To analyze the influence of different demographic and clinical variables in the prevalence of CV disease in subjects affected with RA, PsA, Ps, SLE, or inflammatory bowel disease. Additionally, we compared the adjusted prevalence of CV disease among these conditions. Methods Subjects included in this cross-sectional study were collected as part of the Immune-Mediated Inflammatory Disease Consortium (IMIDC) between 2007 and 2010. Demographic, disease and cardiovascular related clinical data was collected using a standard protocol of questionnaires, after a clinical interview with close questions and review of medical records. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition, and the overall IMIDC, respectively. Standardize prevalence (SP) for each IMID was calculated using marginal analysis. Results 9951 patients were included. When analyzed separately, traditional CV risk factors had a different contribution to CV disease in each IMID. Overall, when analyzed all subjects, older age at study, longer elapsed time from IMID diagnosis to study, presence of traditional CV risk factors (arterial hypertension, type2 diabetes mellitus, dyslipidemia, obesity) and male gender were independently associated with a higher CV disease risk. After adjusting by demographic and traditional CV risk factors, SLE exhibited the highest SP, followed by RA and Ps/Crohn9s disease. Conclusions Cardiovascular disease is related to immune-mediated inflammatory diseases. A different impact is shown dependent of particular disease directly affecting the burden of disease. Acknowledgements We would like to thank all the patients and physicians for their collaboration. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease. A genetic component has been implicated in atherosclerosis. Recently, the ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807 polymorphisms have been associated with coronary artery disease [1] and the PIK3CG rs17398575, EDNRA rs1878406 variants with carotid plaques in general population [2]. Objectives We aimed to determine the potential role of these 5 polymorphisms and cIMT, presence/absence of carotid plaques and CV events in RA. Methods Polymorphisms were analyzed in 2140 Spanish RA patients by TaqMan assays. Subclinical aterosclerosis was determined by carotid ultrasonography (US) in 620 patients. Results No statistical significant differences were observed when the ABO rs579459, PPAP2B rs17114036 and ADAMTS7 rs3825807 polymorphisms and CV events were compared. It was also the case when PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms and cIMT and carotid plaques were analyzed. Conclusions Our results do not confirm an association of these 5 polymorphisms and subclinical atherosclerosis and CV in RA. References Schunkert H, et al. Nat Genet 2011;43:333-8. Bis JC, al. Nat Genet 2011;43:940-7. Acknowledgements This study was supported by European Union FEDER funds and “Fondo de Investigaciόn Sanitaria” (PI06/0024, PS09/00748 and PI12/00060) from `Instituto de Salud Carlos III” (ISCIII, Spain). It was also partially supported by RETICS Programs RD12/0009/0013 and RD12/0009/0004 (RIER) from ISCIII and by grants from the European IMI BTCure Program. RLM is a recipient of a Sara Borrell postdoctoral fellowship from ISCIII (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER). MGB is a beneficiary of a grant from Fundaciόn Espanola de Reumatologia (FER). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1760

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased mortality and reduced life expectancy compared with the general population. This mortality gap has increased in the last years since mortality rates for RA have remained constant throughout time while mortality rates for the general population have decline. Excess mortality has been associated with disease activity. Radiographic joint destruction reflects the cumulative burden of inflammation and it is conceived as an objective measure of RA severity. Objectives The objective of our study is to analyze the influence of radiological joint damage in the mortality rate in a cohort of RA patients. Methods We included 783 RA patients in a retrospective longitudinal study, from May 1993 to November 2013, attending the rheumatology outpatient clinic of the Hospital Clinico San Carlos (Madrid, Spain). Subjects were included at the moment of their first X-ray, until October 2012, and followed until patients9 death, loss of follow up or November 2013. Clinical records were examined and demographic and clinical data was collected. Radiographic joint damage of hands and wrists was assessed with the Sharp vand-der-Heijde score [total (SHS), erosion (ES) and narrowing/(sub)luxation (NSLS) components]. Survival techniques were applied to estimate the mortality rate (MR; expressed per 1000 patients-years with a 95% of Confidence Interval [95% CI]). Cox bivariate and multivariate regression models were conducted to examine risk factors for death. Interaction terms between radiological damage and rheumatoid factor (RF) positivity, and the elapsed time from RA onset to X-ray, were introduce in the models. Proportional hazard assumption was tested using Schoenfeld residuals and the scaled Schoenfeld residuals. Results were expressed as hazard ratio (HR) and 95% CI. Results Most of the patients included were women (74%), with a median age of 61 years old (interquartile range [IQR]: 47-71), 67% were RF positive, and the median (IQR) elapsed time between RA symptoms onset and the X-ray was 2 (0-7) years. The median (range) followed up time per patient was 5 [0.4-20] years. 92 patients died during a follow up time of 4758 person-years. Mortality rate was 19 per 1000 patient-year [95% CI 16-24]. We observed in the bivariate analysis that older age, male sex, higher elapsed time from RA onset to X-ray, SHS, ES, NSLS, number of hospital admissions (used as a surrogate measure of comorbidity), basal Health Assessment Questionnaire, RF positivity, earlier RA onset (in calendar time), and no treatment with biological therapy, were associated with a higher MR. 3 multivariate models were constructed, using SHS, ES or NSLS as measures for joint destruction, and adjusted by the previous variables. In none of the models radiographic damage was associated with MR. However, we observed that the interaction between ES and RF positivity and with elapsed time from RA onset to X-ray were both significant (p=0.001, p=0.03, respectively): the lower elapsed time, the greater the effect of ES in the MR. On the other hand, ES was associated to MR only in RF negative patients. Conclusions Erosive joint damage seems to be a risk factor for all cause mortality among RF negative RA patients. Early radiographic damage seems to better predict mortality. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5198

Background With the expanding use of Biological Agents (BA), in particular TNF inhibitors, opportunistic infections (OI) are a major concern in Rheumatology. Objectives a) To describe the incidence of OI global and by periods in Rheumatoid Arthritis (RA). b) To compare the risk of OI by BA. Methods We performed a retrospective longitudinal observational study from 1/1/2000 to 23/11/2013. We included subjects followed up in our outpatient clinic, diagnosed with RA according to ACR criteria 87, whom started treatment with a BA [etanercept (ETN), golimumab (GOLI), certolizumab (CTZ), infliximab (IFX), adalimumab (ADA), rituximab (RTX), abatacept (ABA), or tozilizumab (TZL)]. Our primary end point was OI that involved the suspension of the BA. We consider OI when there was a positive culture (for Candida, Aspergillus or Herpes) or compatible symptoms that responded to specific treatment. We also collected secondary variables: sociodemographic (age, sex); clinical (disease duration, types of BA, hospital admission, previous BA). Statistical analysis: We used survival techniques to estimate the incidence of global OI and OI by periods (1st: 98-2002, 2nd:2002-2007, 3rd: 2007-2013), expressed per 1000 patient-year [CI 95%]. The exposure time was defined from the start date of each BA to suspension, loss of follow up or end of study (23/11/2013). We performed Cox regression models (adjusted by age, duration of RA, sex, calendar time and prior BA) to compare the risk of OI between each BA. Results 405 RA patients were included in the study, they started 744 different courses of BA treatment, with a total follow-up of 1,612 patient-years. Of these, 81% were women with a mean age at diagnosis of 52.5±13 years. The most frequently used drug was ADA (32%), followed by ETN (25%), IFX (21%) and RTX (14%). There were 16 OI (6 Candidas, 2 Aspergillus and 8 Herpes Zoster), 40% required hospitalization and two died of disseminated candidiasis. The incidence of OI was 9.9 [6.1-16.2], and tended to increase over time (1st: 5.9 [1.5 to 23.9]; 2nd: 7.7 [2.9 to 20, 6]; and 3rd: 13.1 [7.1 to 24.3]). We only registered OI cases in anti-TNF and RTX, which is the drug with higher incidence (n=3, I: 20.1 [6.4 to 62.4]). We found no statistically significant association between RTX compared with other BA and the development of OI Conclusions The incidence of OI and its evolution over time in real life conditions is described. It seems that OI tend to increase over time and we had two cases with fatal outcome. Doctors using BA should be concerned about this problem and be aware of the optimal methods for the detection and management of OI. We did not find statistical differences in the rate of OI between BA. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4509

Background Fibromyalgia (FM) is a condition characterized by chronic widespread pain associated to multiple symptoms, including fatigue, sleep disturbances, cognitive dysfunction, and depressive episodes. In recent years, many candidate gene association studies have been designed and carried out to identify the genes associated with FM. However, the study of the genetic factors associated to disease severity or to the presence of coexisting comorbidities, and therefore, potentially useful as predictors of disease outcome, is a relatively unexplored field. Objectives To study in FM patients the genetic risk factors involved in the presence of syndromes and symptoms associated with this disease, and/or severity. Methods We included Spanish Caucasian patients diagnosed with FM according to 1990 ACR criteria. Fist, we used a discovery cohort (DC) of 564 patients, recruited from 15 centers throughout the Spanish geography. Subsequently, we used a replication cohort (RC) of 397 patients from the DNA Bank for Genetic Research in FM and Chronic Fatigue Syndrome of the FF Foundation and from the National DNA Bank (Salamanca, Spain). In the DC we studied the association between 320 single nucleotide polymorphisms (SNPs), located in 22 loci, and the presence of symptoms and syndromes associated with FM (depression, headache, sleep disorders, myofascial syndrome, irritable bowel syndrome, chronic fatigue, vertiginous syndrome, chronic cystitis, and sicca syndrome) and disease severity, using the FIQ (Fibromyalgia Impact Questionnaire) and the HADS (Hospital Anxiety and Depression Scale). In the RC, we studied those SNPs and those variables that were associated in the discovery cohort. As the dependent variables were dichotomous or continuous, linear or logistic regressions were performed, respectively, to study the genetic association, using an additive model of effects. The odds ratio (OR), with 95% confidence intervals [95% CIs], was used to assess the strength of association between genotypes and the main dichotomous variables. Analyses were adjusted for sex and time from the onset of pain symptoms. P values were adjusted for the number of main variables and a cutoff of 0.05 was established to select those SNPs to replicate in the RC. DC and RC results were pooled using meta-analysis techniques. P value was corrected considering the number of linkage disequilibrium blocks in which the analyzed SNPs were included. Results In the DC, we observed 10 SNPs with an adjusted p-value lower that 0.05: rs4760750, rs4760816, rs2171363 (associated to sleep disturbances), rs174696, rs10171225, rs3771863 (associated to sicca syndrome), rs2422148, rs2216307 (associated to vertigo), and rs12654778, rs10434128 (associated to HADS depression). After replication in the RC and pooling the results from both cohorts, only the rs3771863 variant, from the TACR1 gene, showed a significant association with a lower risk of sicca syndrome (adjusted OR 0.56 [95% CI 0.42 - 0.76], p=0.00022). Conclusions TACR1 gene could play a role in the development of sicca syndrome in FM patients. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5542

International audience; Objective To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the RA genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. Methods We analyzed a total of 11,715 RA cases and 26,493 controls from 9 independent cohorts, all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on OPN expression in macrophages and OPN serum levels was investigated. Results We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of ≥ 3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (P = 1.29x10-5, ORACPA-negative 1.257 1.135–1.394) and less with ACPA positivity (P = 0.0148, ORACPA-positive 1.072 1.014–1.134]). The odds ratios between these subgroups (i.e., ACPA-positive and -negative) significantly differed (P = 7.33x10-3). Expression quantitative trait locus analysis revealed an association of the SPP1 risk-allele combination with decreased SPP1 expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the SPP1 risk-allele combination and low serum level of secreted OPN (P = 0.0157) as well as serum level of secreted OPN correlated positively with ACPA production (P = 0.005; r = 0.483). Conclusion We demonstrate a significant contribution of the combination of SPP1 rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association greater in patients negative for ACPAs.

Background CD226 genetic variants have been associated with a number of autoimmune diseases. Objectives The aim of this study was to investigate the potential implication of the CD226 loci in the susceptibility to and main clinical manifestations of giant cell arteritis (GCA). Methods A Spanish Caucasian cohort of 455 patients diagnosed with biopsy-proven GCA and 1414 healthy controls were included in the study. Three CD226 polymorphisms, rs727088, rs34794968 and rs763361, were genotyped using the TaqMan® allelic discrimination technology. PLINK software was used for the statistical analyses. Results No significant association between the CD226 polymorphisms and susceptibility to GCA was found (rs727088: P =0.92, OR=1.01 CI 95% 0.86-1.18; rs34794968: P =0.61, OR=1.04 CI 95% 0.89-1.22; rs763361: P =0.88, OR=0.99 CI 95% 0.84-1.16). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischemic manifestations or irreversible occlusive disease, no association was observed either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. Furthermore, the haplotype analysis revealed no significant association with the disease. Conclusions Our results show that the CD226 gene does not play a relevant role in the susceptibility to GCA and clinical manifestations of this vasculitis. References Hafler JP, Maier LM, Cooper JD, Plagnol V, Hinks A, Simmonds MJ, et al. CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun. 2009; 10:5-10. Lofgren SE, Delgado-Vega AM, Gallant CJ, Sanchez E, Frostegard J, Truedsson L, et al. A 3’-untranslated region variant is associated with impaired expression of CD226 in T and natural killer T cells and is associated with susceptibility to systemic lupus erythematosus. Arthritis Rheum. 2010; 62:3404-3414. Salvarani C, Cantini F, Boiardi L, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 2002; 347:261-271. Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ, Miranda-Filloy JA, Gonzalez-Juanatey C, Martin J, et al. Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum. 2009; 61:1454-1461. Disclosure of Interest None Declared

Background Rheumatoid arthritis (RA), a chronic autoimmune disease, is associated with accelerated atherosclerosis. Results from GWAS of UK, US and European families with RA (1,2,3) have identified linkage to the chromosome 16p13 locus. MHCIITA is a major regulator of MHC expression that has also been reported to be involved in the susceptibility to myocardial infarction (4). Objectives In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA. Methods 1302 patientsfulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively. Results No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events or not were found. It was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination ( p =0.08; OR: 0.63 [95%CI: 0.37- 1.05]). Conclusions Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of RA patients. Acknowledgments: Supported by two grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spain). This work was partially supported by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+i 2008-2011 (FEDER). MGB is a recipient of a grant from Fundaciόn Espanola de Reumatologia (FER). References Mackay K, Eyre S, et al. Arthritis Rheum 2002; 46:632-9. John S, Shephard N, et al. Am J Hum Genet 2004; 75:54–64. Eyre S, Barton A, et al. Arthritis Rheum 2004; 50:729–35. Swanberg M, Lidman O, et al. Nat Genet 2005; 37:486-94. Disclosure of Interest None Declared

Background The T-cell receptor T3 zeta chain ( CD3 ζ), also called CD247, is essential for assembly, surface expression and signaling cascade of the T-cell receptor-CD3 complex (TCR/CD3 complex). Abnormalities in this pathway can result in T-cell dysfunction and development of autoimmune disorders [1]. Regarding this, previous reports have demonstrated an association of CD247 variants with systemic lupus erythematosus [2, 3] and systemic sclerosis [4, 5]. In the case of rheumatoid arthritis (RA), one meta-GWAS found no association between CD247 gene and RA at a genome-wide level of significance [6], however, a more recent meta-analysis of GWAS on RA and celiac disease (CeD) identified CD247 gene as a new susceptibility locus for RA [7]. Objectives In order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537) in a large independent European Caucasian population. Results However, no evidence of association was found for these three CD247 SNPs with RA and with the anti-cyclic citrullinated polypeptide (anti-CCP) status. We performed a meta-analysis including GWAS data for the rs864537 from previously published data, reveling an overall genome-wide significant association between rs864537 and RA with anti-CCP (OR 0.90 [0.87 to 0.93], P overall = 2.1 x 10 -10 ). Conclusions Our results described for first time at GWAS-level the association of this CD247 variant and RA risk References Takeuchi T et al . Ann Rheum Dis . 2012; 71:i78-i81. Gorman CL et al . J Immunol . 2008; 180: 1060-70. Warchol T et al . Tissue Antigens . 2009; 74:68-72. Dieude P et al . Ann Rheum Dis . 2011;70:1695-6. Radstake TR et al . Nat Genet . 2010; 42:426-9. Stahl EA et al . Nat Genet . 2010; 42:508-14. Zhernakova A et al . PLoS Genet . 2011; 7:e1002004. Acknowledgements This work was supported by two Spanish grants from RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+i 2008-2011 (FEDER) and also by grants from the European IMI BTCure Program. MT was supported by Spanish Ministry of Science through the program Juan de la Cierva (JCI-2010-08227). Disclosure of Interest None Declared