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Introduction: Patients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients. Methods: A large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA. Results: Low irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ?4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01). Conclusions: Our results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA. FUNDING: This work was partially supported by grants from Instituto de Investigación Sanitaria IDIVAL (NVAL17/10) and from the ‘Asociación Cántabra de Reumatologıá ’ awarded to FG. FG and JR-G are beneficiaries of a grant funded by ‘Instituto de Salud Carlos III’ (ISCIII) (PI20/00059). FG is supported by funds of the RICORS Program (RD21/0002/0025) from ISCIII, co-funded by the European Union. SR-M and VP-C are supported by funds of the RETICS Program (RD16/0012/0009) from ISCIII, co-funded by the European Regional Development Fund. RL-M is a recipient of a Miguel Servet type II Program fellowship from ISCIII, co-funded by the European Social Fund, `Investing in your future´ (CPII21/00004). ACKNOWLEDGMENTS: We are indebted to the patients for their essential collaboration to this study.

Background:The prevalence of inflammatory bowel disease (IBD) in ankylosing spondylitis (AS) has been reported to range between 6%-15%. As occurs with axial spondyloarthrtitis (axSpA), patients with IBD have an increased risk of cardiovascular (CV) events because of a process of accelerated atherosclerosis1. However, it is unknown whether the presence of IBD confers an increased cardiovascular CV risk in patients with axSpA.Objectives:To compare the atherosclerotic burden, CV events, CV risk factors and disease related factors including structural damage in axSpA patients with and without IBD.Methods:Cross-sectional analysis of the AtheSpAin cohort, a Spanish multicenter cohort designed for the study of atherosclerosis in axSpA, comparing axSpA patients with and without concomitant IBD. Background information on CV and disease-related factors was reviewed. Data on CV risk and disease status at the time of the study were also obtained, including the structural damage assessed by the presence of syndesmophytes, the severity of the sacroiliitis (defined as grade 3 or 4 according to New York criteria), and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Carotid ultrasound (US) was performed in all patients at the time of the study, including measurement of carotid intima-media wall thickness (cIMT) and plaque detection according to the Mannhein consensus criteria.Results:A set of 886 axSpA patients were included. 829 (93.6%) of them had no concomitant IBD, which was present in 57 (6.4%) patients. Age, sex and AS/nr-axSpA ratio were comparable in both groups (Table 1. next page). Patients with IBD were characterised by a lower prevalence of HLA B27 (46% vs 72%, p=0.01) and a higher presence of concomitant psoriasis (21% vs 10%, p=0.01)Regarding peripheral disease (history of synovitis, enthesitis, dactylitis) and hip involvement, no differences were found between both groups. There were either no differences in the structural damage found in patients with and without IBD (Table 1. next page).With respect to the management of the disease, prednisone (21% vs 13%, p = 0.03), DMARDs (54% vs 35%, p = 0.01) and anti-TNFα therapy (54% vs 31%, p = 0.00) were more commonly used in the group with IBD, while treatment with NSAIDs was more frequent in patients without IBD (81% vs 70%, p = 0.04).Regarding CV risk features, smoking was more frequent in patients without IBD (34% vs 21%, p = 0.045) (Table 1. next page). No differences were observed neither in the lipid profile or blood pressure at the time of the study, nor in the prevalence of CV events (5% vs 4%, p=0.99) (Table 1) and the subclinical atherogenic burden assessed both by the presence of carotid plaques (31% vs 37%, p=0.45) and the cIMT (645 ± 147 mm vs 636 ± 112 mm, p = 0.64) (Table 1. next page).Conclusion:The presence of IBD does not confer additional CV risk to axSpA. In our series, patients with axSpA and IBD showed a lower frequency of HLA B27 and a higher prevalence of psoriasis.Table 1.axSpA without IBD (n=829)axSpA with IBD (n=57)pMen/Women, n272/55715/420.33Mean age (years) ±SD at the time of study49 ± 1349 ± 100.99AS/nr-AxSpa656/17345/120.97History of CV risk factors Current smoker285 (34)12 (21)0.045 Obesitty Dyslipemia280 (34)16 (28)0.42 Hypertension223 (27)16 (28)0.79 Diabetes Mellitus60 (7)4 (7)0.99 Chronic Kidney Disease20 (2)2 (4)0.65History of cardiovascular events, n (%)40 (5)2 (4)0.99Structural damage at the time of studyPresence of syndesmophytes, n (%)307 (37%)23 (49%)0.66mSASSS5 (1-15)6 (3-23)0.64Severe sacroiliitis (grade 3,4), n (%)436 (53)34 (60)0.42CV data at the time of studyCarotid plaques261 (31)21 (37)0.45IMT (mm)645 ± 147636 ± 1120.64IMT >= 0.9 mm46 (6)0 (0)0.066Abbreviations: AS = ankylosing spondylitis. AxSpA= axial spondylitis. CV = cardiovascular. IBD = Inflammatory bowel disease. IMT = intima-media wall thickness. Nr-axSpA = no-radiographic axial spondylitis.Disclosure of Interests:None declared

The clinical diagnosis of von Willebrand disease (VWD), particularly type 1, can be complex because several genetic and environmental factors affect von Willebrand factor (VWF) plasma levels. An estimated 60% of the phenotypic variation is attributable to hereditary factors, with the ABO blood group locus being the most influential. However, recent studies provide strong evidence that nonsynonymous single nucleotide variants (SNVs) contribute to VWF and factor VIII phenotypic variability in healthy individuals. This study aims to investigate the role of common VWF SNVs on VWD phenotype by analyzing data from 219 unrelated patients included in the “Molecular and Clinical Profile of von Willebrand Disease in Spain project.” To that end, generalized linear mixed-effects regression models were fitted, and additive and epistatic analyses, and haplotype studies were performed, considering five VWD-related measures (bleeding score, VWF:Ag, VWF:RCo, factor VIII:C, and VWF:CB). According to these analyses, homozygotes: for p.Thr789Ala(C) would be expected to show 39% higher VWF:Ag levels; p.Thr1381Ala(C), 27% lower VWF:Ag levels; and p.Gln852Arg(C), 52% lower VWF:RCo levels. Homozygotes for both p.Thr789Ala(C) and p.Gln852Arg(T) were predicted to show 185% higher VWF:CB activity, and carriers of two copies of the p.Thr1381Ala(T)/p.Gln852Arg(T) haplotype would present a 100% increase in VWF:RCo activity. These results indicate a substantial effect of common VWF variation on VWD phenotype. Although additional studies are needed to determine the true magnitude of the effects of SNVs on VWF, these findings provide new evidence regarding the contribution of common variants to VWD, which should be taken into account to enhance the accuracy of the diagnosis and classification of this condition. ClinicalTrials.gov identifier: NCT02869074.

Objective.The assessment of the cardiovascular (CV) risk is recommended in patients with chronic inflammatory rheumatic diseases. The objectives of this study were to assess the CV risk profile in a cohort of patients with psoriatic arthritis (PsA), to determine the presence of subclinical cardiovascular disease by carotid ultrasound (US), and to study the association of CV disease to PsA characteristics.Methods.This was a cross-sectional multicentric descriptive study. The clinical CV risk was calculated with Systematic Coronary Risk Evaluation (SCORE) charts. Common carotid US was conducted to evaluate the carotid wall intima-media thickness and the presence of atheroma plaques. Patients were reclassified upon US results. Multivariate analyses were performed to identify associations of US carotid abnormalities with the classical CV risk factors and PsA characteristics.Results.The study included 176 patients with PsA. The SCORE-estimated CV risk was intermediate in 65.3% of the patients. In the US study, 32% of the patients had abnormalities, and 30.8% of the patients were upgraded and reclassified as very high risk owing to the presence of atheroma. Subclinical CV disease was associated with age and dyslipidemia but not with other risk factors. It was associated with axial disease in the subgroup with intermediate risk, and with C-reactive protein levels in patients with high risk.Conclusion.Many patients with PsA have clinical estimated intermediate or high risk of a fatal CV event. A carotid US study detects subclinical vascular disease and may be useful to depict the real risk. The presence of atheroma is only partially explained by the classic CV risk factors.

Background:Osteoporosis (OP) has been described to be frequent in spondyloarthritis [1]. However, the specific association of psoriatic arthritis (PsA) and bone fragility remains inconclusive, with a prevalence of OP ranging from 1.4–68.8 [2, 3].Objectives:The aim of this study was to describe the prevalence of osteopenia and OP in a representative cohort of patients with PsAMethods:Multi-centric, cross-sectional, descriptive study of patients with clinical diagnosis of PsA. Patients were randomly selected; they were invited to participate and were included after signing informed consent until the calculated sample size was reached. Clinical and demographic characteristics were recorded, as well as several protective and risk factors for osteoporosis and insufficiency fractures. Patients were asked to undergo a hip and lumbar (L2-L4) densitometry by DXA, and lateral X-Ray of the dorsal and lumbar spine if they had not these tests available in the previous year. The prevalence of osteoporosis and the risk factors was calculated. The characteristics of the patients with OP were compared to those without by univariate analyses, and were adjusted by age and sex. Multivariate analyse by ANOVA test was done to study the association of OP and fractures with clinical characteristics of the disease. The Clinical Research Ethics Committee of the Hospital General Universitario de Alicante (ISABIAL- approval number 180264) approved the studyResults:166 patients were included (Female 69%, male 30,1%), median age 58 (IR 51-65). Basal characteristics are shown in Table 1. Osteopenia or OP was present in 100 patients (60.2%). OP was present in 44 patients (26.5%). Among these, 9 patients (20.5%), all women ≥50 years old, had a total amount of 14 insufficiency fractures (4 vertebrae, 2 hips, 4 distal radius, 4 others). OP was present in 21.7% of the women, and 4.8% of the men. The most frequent risk factors among patients with OP were D-vitamin deficit (54.5%), sedentary life style by WHO standards (43.2%) and low calcium intake (38.6%). The most frequent protector factors in the group without osteopenia/nor OP was the intake of statins for ≥12 months. The presence of vertebral fractures was associated with female sex, sedentary lifestyle and age.Conclusion:The prevalence of insufficiency fractures among PsA patients was very superior to that recently found in the general population in Spain (prevalence 1.83%) [4]. Fractures are associated, similar to the general population, to female sex, sedentary life and age. Inherent factors to psoriatic disease may be responsible for this increased prevalenceReferences:[1]Moltó A et al. Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study. Ann Rheum Dis. 2016;756:1016[2]Gulati AM et al. Bone mineral density in patients with psoriatic arthritis: data from the Nord-Trøndelag Health Study 3. RMD Open. 2017;3: e000413.[3]Busquets N et al. Bone mineral density status and frequency of osteoporosis and clinical fractures in 155 patients with psoriatic arthritis followed in a university hospital. Reumatol Clin. 2014;10:89.[4]Seoane-Mato D et al. Prevalence of rheumatic diseases in adult population in Spain (EPISER 2016 study): Aims and methodology. Reumatol Clin. 2019;15:90.Table 1.Basal characteristics (n=166)Age (years)57,9 (SD 0,8)Median 58 (IR 51-65)SexMale50 (30.1%)Female116 (69.9%)Duration of disease (years)10.3 (SD 0.63)Median 9 (IR 4.75-13)Type of PsAAxial15 (9%)Peripheral125 (75.3%)Both26 (15.7%)HAQ (n=142)0.47 (SD 0.05)Median 0.25 (IR 0-1)BASFI (n=40)3.7 (SD0.5)Median 3.6 (IR 1-5.75)cDMARDNever25 (15.1%)Previous/actual141 (85%)bDMARDNever84 (50.6%)Previous/actual82 (49.4%)PsA: psoriatic arthritisHAQ: Health Assessment QuestionnaireBASFI: Bath Ankylosing Spondylitis Functional IndexcDMARDs: classical disease modifying anti-rheumatic drugsbDMARDs biological drugsAcknowledgements:Thanks to doctors C. Fernández-Carballido, M Mínguez and G Panadero for their help recruiting candidates.Disclosure of Interests:None declared.

Background:Anterior uveitis (AU) is one of the most frequent extra articular manifestations of axial spondyloarthritis (axSpA), present in around 25% of patients. As with axSpA, AU has also been associated with the development of accelerated atherosclerosis1. If the presence of AU confers an increased cardiovascular (CV) risk or specific disease-related features to patients with axSpA remains unclear.Objectives:To compare the atherosclerotic burden, CV events, CV risk factors and disease related factors including structural damage in axSpA patients with and without AU.Methods:Cross-sectional analysis of the AtheSpAin cohort, a Spanish multicenter cohort designed for the study of atherosclerosis in axSpA, comparing axSpA patients with and without concomitant uveitis. Background information on CV and disease-related factors was reviewed. Data on CV risk and disease status at the time of the study were also obtained, including the structural damage assessed by the presence of syndesmophytes, the severity of the sacroiliitis (defined as grade 3 or 4 according to New York criteria), and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Carotid ultrasound (US) was performed in all patients at the time of the study, including measurement of carotid intima-media wall thickness (cIMT) and plaque detection according to the Mannhein consensus criteria.Results:A set of 886 axSpA patients were included. 709 (80.0%) of them had no history of concomitant AU, which was present in the remaining 177 (20.0%). The group with AU was older (50 ± 11 vs 48 ± 13 years, p=0.05), had a higher proportion of patients with AS (90.1% vs 76.3%, p=0.00) (Table 1) and a longer disease duration 13(7-23) vs 7(2-16) years, p=0.00]. The prevalence of HLA-B27 was higher in AU patients (82% vs 67%).Remarkably, structural damage showed interesting differences between both groups (Table 1). AU patients had a higher prevalence of severe sacroiliits (69% vs 49%, p=0.00), which remained significant after adjustment for age, disease duration and AS/nr-axSpA ratio. Furthermore, a non-significant trend towards a higher prevalence of syndesmophytes (44% vs 36%, p=0.06) and hip involvement (20% vs 15%, p=0.09) was observed in the group of AU.Regarding CV risk features, no differences were observed in the prevalence of CV risk factors and events (Table 1). Patients with AU showed a higher cIMT in the crude analysis (665 ± 156 mm vs 640 ± 142 mm, p = 0.047), but no significant differences were observed after adjustment by age and sex (p=0.6). Prevalence of carotid plaques was comparable in both groups (32% Vs 32%, p=0.84).Table 1.axSpA without uveitis (n=709)axSpA with uveitis (n=177)pP (adjusted model)Men/Women, n477/232122/550.68Mean age (years) ±SD at the time of study48 ± 1350 ± 110.049AS/nr-AxSpa541/168160/170.000History of CV risk factors, n (%) Current smoker247 (35)50 (28)0.096 Obesitty Dyslipemia233 (33)63 (36)0.48 Hypertension188 (27)50 (28)0.63 Diabetes Mellitus50 (7)14 (8)0.69 Chronic Kidney Disease18 (3)4 (2)0.99History of cardiovascular events, n (%)29 (4)12 (7)0.13Structural damage at the time of studyPresence of syndesmophytes, n (%)253 (36)77 (44)0.063mSASSS5 (1-15)6 (0-16)0.31Severe sacroiliitis (grade 3,4), n (%)348 (49)122 (69)0.0000.000*Carotid US data at the time of studyCarotid plaques, n (%)225 (32)57 (32)0.84IMT (mm)640 ± 142665 ± 1560.0470.6**IMT >= 0.900 mm36 (5)10 (6)0.72*: adjusted by age, disease duration and AS/nr-axSpA ratio**: adjusted by age and sexAbbreviations: AS = ankylosing spondylitis. AxSpA= axial spondylitis. CV = cardiovascular. IMT = intima-media wall thickness. Nr-axSpA = no-radiographic axial spondylitis.Conclusion:The presence of AU does not confer additional CV risk to axSpA patients, although it is associated with a more severe structural damage in our series.References:[1]Conkar S, Güven Yilmaz S, Koska İÖ, Berdeli A, Mir S. Evaluation of development of subclinical atherosclerosis in children with uveitis. Clin Rheumatol. 2018 May;37(5):1305-1308.Disclosure of Interests:None declared

Background:Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA).1 Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients,2 we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce.3Objectives:To evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA.Methods:510 patients who fulfilled the ASAS criteria for axSpA4 were included in this study. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242 T/A, rs7159023 G/A and rs35262691 T/C) were genotyped by TaqMan probes. Serum vaspin levels were assessed by Enzyme-Linked ImmunoSorbent Assay. Analysis was performed using a statistical software.Results:Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (pConclusion:Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.References:[1]Adv Exp Med Biol. 2019;1111:159-88.[2]Front Med (Lausanne). 2018;5:62.[3]Braz J Med Biol Res. 2016;49(7):e5231.[4]Ann Rheum Dis. 2009;68(2):ii1-44.Acknowledgements:Personal funds: RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF); SR-M: RD16/0012/0009 (ISCIII-ERDF); VP-C: PREVAL18/01 (IDIVAL); LL-G: INNVAL20/06 (IDIVAL).Disclosure of Interests:Javier Rueda-Gotor: None declared, Raquel López-Mejías: None declared, Sara Remuzgo-Martínez: None declared, Verónica Pulito Cueto: None declared, Alfonso Corrales: None declared, Leticia Lera-Gómez: None declared, Virginia Portilla: None declared, Iñigo González-Mazón: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Rosa Expósito: None declared, Cristina Mata: None declared, Javier Llorca: None declared, Vanessa Hernández-Hernández: None declared, Carlos Rodríguez-Lozano: None declared, Nuria Barbarroja Puerto: None declared, Rafaela Ortega Castro: None declared, Noelia García Castañeda: None declared, Cristina Fernández-Carballido: None declared, Maria Paz Martínez-Vidal: None declared, David Castro-Corredor: None declared, Joaquín Anino-Fernández: None declared, Diana Peiteado: None declared, Chamaida Plasencia: None declared, E Galindez: None declared, María L. García Vivar: None declared, Oreste Gualillo: None declared, Juan Carlos Quevedo-Abeledo: None declared, Santos Castañeda: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay Speakers bureau: Pfizer, Abbvie, MSD, Grant/research support from: Pfizer, Abbvie, MSD, Fernanda Genre: None declared

Background:Patients with axial spondyloarthritis (axSpA) may present with concomitant psoriasis (Ps) in approximately 10% of cases. As with axSpA, Ps is also associated with an accelerated atherosclerosis process1. However, it is unknown whether the presence of Ps confers an increased cardiovascular (CV) risk in patients with axSpA.Objectives:To compare factors related to the disease, CV risk factors, atherosclerotic burden, and CV events in patients with axSpA with and without Ps.Methods:Cross-sectional analysis of the AtheSpAin cohort, a Spanish multicenter cohort designed for the study of atherosclerosis in axSpA. We compared axSpA patients with and without concomitant psoriasis, focusing mainly on CV risk characteristics. Background information on CV risk factors, CV events, and disease-related factors was reviewed, and data on maximum body index, blood pressure, lipid profile, and disease status at the time of the study were also obtained. Carotid ultrasound (US) was performed in all patients at the time of the study, including measurement of carotid intima-media wall thickness (cIMT) and plaque detection according to the Mannhein consensus criteria.Results:A set of 882 axSpA patients were included. 786 (89.1%) of them had no concomitant Ps, which was present in 96 (10.9%) patients. Although the mean age was similar, male sex was more prevalent in axSpA patients with Ps (79.1% Vs 66.5%, p=0.01) (Table 1).Furthermore, it was found that axSpA with Ps had a more frequent history of synovitis (50% vs 33%, p = 0.001), dactylitis (13% vs 6%, p = 0.011) and concomitant inflammatory bowel disease (13% vs 6%, p = 0.01). AxSpA patients with Ps had a non-significant trend towards a higher prevalence of asymmetric sacroiliitis (23 vs 16%, p = 0.064) and had a lower frequency of positive HLA-B27 status (56% vs 72%, p = 0.003). Regarding the management of the disease, prednisone (23% vs 12%, p = 0.02), methotrexate (30% vs 15%, p = 0.000) and anti-TNFα therapy (50% vs 34%, p = 0.002) were more commonly used in the group with Ps.Regarding CV risk characteristics, no differences were observed either in the prevalence of traditional CV risk factors (Table 1), nor in the total serum level, HDL and LDL, blood pressure and body mass index at that time of the study. However, axSpA patients with Ps showed a higher prevalence of CV events (9% vs 4%, p = 0.05), including ischemic heart disease (6% vs 3%, p = 0.042) and ischemic stroke (4% vs 1%, p = 0.016) (Table 1). The subclinical atherogenic burden was also more severe in the group with Ps, with a higher prevalence of carotid plaques (39% vs 31%, p = 0.098), and higher values of cIMT (0.664 ± 0.170 mm vs 0.642 ± 0.142 mm, p = 0.16), although the differences did not reach statistical significance.Table 1.Main sociodemographic and cardiovascular differences among axSpA patients with and without psoriasis.axSpA without psoriasis (n=786)axSpA with psoriasis (n=96)pMen/Women, n523/26876/200.010Mean age (years) ±SD at the time of study49 ± 1349 ± 130.81AS/nr-AxSpa625/16677/190.79History of CV risk factors Current smokers267 (34)30 (31)0.60 Obesitty174 (22)26 (27)0.29 Dyslipidemia262 (33)35 (36)0.48 Hypertension211 (27)28 (29)0.57 Diabetes Mellitus56 (7)8 (8)0.65 Chronic Kidney Disease19 (2)3 (3)0.72History of cardiovascular events, n (%)33 (4)9 (9)0.023 Ischemic heart disease20 (3)6 (6)0.042 Congestive heart failure2 (0)1 (1)0.29 Ischemic stroke6 (1)4 (4)0.016 Peripheral artery disease6 (1)0 (0)0.99CV data at the time of studyCarotid plaques244 (31)38 (39)0.098IMT mm0.642 ± 0.1420.664 ± 0.1700.16IMT >= 900 mm40 (5)6 (6)0.66Abbreviations: AS = ankylosing spondylitis. AxSpA= axial spondylitis. CV = cardiovascular. IMT = intima-media wall thickness. Nr-axSpA = no-radiographic axial spondylitis.Conclusion:The presence of Ps may confer additional CV risk to axSpA patients and is associated with particular disease related factors.References:[1]Fang N, Jiang M, Fan Y. Association Between Psoriasis and Subclinical Atherosclerosis: A Meta-Analysis. Medicine (Baltimore). 2016;95(20):e3576.Disclosure of Interests:None declared.

Background:During the last decades, anxiolytics and antidepressants (ADP) have been among the most prescribed therapies in all developed countries (1). In Spain a prevalence of use of 11.4% was communicated (2), slightly over the European average (3,4). They have potential addiction problems and side effects.Objectives:The objective of this study was to evaluate the prevalence of anxiolytics and antidepressants among patients who attend a Rheumatology consult, as well as the indication for them.Methods:Patients who were referred for the first time to the Rheumatology consult were included. Demographical data, reason for referral and final diagnosis were recorded. Regarding the treatment with ADP or/and benzodiazepines (BDZ), their duration and the indication for the prescription were recorded. Sample size was estimated for a 0.05% alpha risk. Descriptive, univariate and multivariate analyses (ANOVA) were performed in order to study the prevalence of these treatments, and their associations with demographical or clinical characteristics. The study was approved by the Hospital Universitario de Elche Ethics Committee.Results:350 patients were included (women 77.1%, men 22.9%), mean age 58.1 yo. 40% were occupied and 31.4% were unemployed. The majority were married or lived with a couple (71.4%). Most of them had been referred for musculoskeletal pain (73.4%). More than a third (39.4%) were on BZD and/or ADP: 107 patients were on BZD (30.6%), 68 were on ADP (19.4%), and 47 (13.4%) were on both. The most frequent reasons for their prescription were anxiety, depression and insomnia. The final diagnosis in the clinic was a non-inflammatory condition in 53.1%, and inflammatory in 18%. In the univariate analyses, the use of BZD/ADP was not associated with civil status, but it was associated with female sex (pConclusion:The use of anxiolytics and antidepressants is frequent in the patients referred to the Rheumatology clinic, and it’s associated to female sex and non-inflammatory conditions, over all fibromyalgia.References:[1]Lagnaoui R, Depont F, Fourrier A, Abouelfath A, Bégaud B, Verdoux H, et al. Patterns and correlates of benzodiazepine use in the French general population. Eur J Clin Pharmacol. 2004;60:523-9.[2]Ministerio de Sanidad, Servicios Sociales e Igualdad. Secretaría de Estado de Servicios Sociales e Igualdad. Delegación del Gobierno para el Plan Nacional sobre Droga. Encuesta sobre alcohol y drogas en población general en España: EDADES 2011-2012. 2013. Disponible en:http://www.pnsd.msc.es/Categoria2/observa/pdf/EDADES2011.pdf[3]Simó Miñana J. Utilización de medicamentos en España y en Europa. Aten Primaria. 2012; 44:335-47.[4]Khong TP, de Vries F, Goldenberg JS, Klungel OH, Robinson NJ, Ibáñez L, Petri H. Potential impact of benzodiazepine use on the rate of hip fractures in five large European countries and the Unite d States Calcif Tissue Int. 2012;91:24-31.Disclosure of Interests: :None declared

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

Background: Eltrombopag is effective and safe for treating chronic immune thrombocytopenia (ITP) patients who have not responded to previous therapy. Interestingly, some patients in whom hemostatic platelet counts are achieved with eltrombopag may sustain the platelet response when eltrombopag ceases to be administered. However, the frequency of sustained responses after discontinuing eltrombopag without additional therapy for ITP is largely unknown. Methods: A total of 260 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry were retrospectively evaluated. The study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age was 62 [range, 18–93] years. There were 165 women and 95 men. According to the standard definition, patients were allocated to newly diagnosed (n=29), persistent (n=36) and chronic (n=195) ITP groups. The median time from diagnosis to eltrombopag initiation was 24 [range, 1–480] months. The median number of previous therapies was 3 [range, 0–10], including splenectomy (22%), rituximab (23%) and romiplostim (19%). The initial response rate to eltrombopag was 231/260 (89%), including 77% (n=201) cases of complete remission (platelet count ≥100 x 109/L). The median duration of eltrombopag treatment was 6 [range, 1–54] months. Eltrombopag was discontinued in 80 out of 201 (39.8%) patients who achieved CR. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=33), platelet count >400x109/L (n=29), patient’s request (n=5), aspartate aminotransferase elevation (n=3), diarrhea (n=3), thrombosis (n=3) and other reasons (n=4). For analysis of discontinuation, patients with follow-up < 6 months (n=15), newly diagnosed ITP (n=11) or patients who received concomitant or previous (6 months before) treatments at the start of eltrombopag use (n=5) were excluded. Of the 49 evaluable patients, 22 (45%) had an immediate relapse after stopping eltrombopag. One patient with sustained response after stopping treatment relapsed at 10 months. A total of 26 patients (53%) showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 [range, 6–25] months. These patients were characterized by a median time since ITP diagnosis of 46.5±114.1 months, with 4/26 having ITP The main characteristics (age, gender, duration of ITP, prior anti-ITP lines, prior splenectomy, prior rituximab, prior romiplostim, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 26 patients with sustained response after stopping eltrombopag were compared with those of the 23 patients relapsing after eltrombopag withdrawal. No predictive factors of sustained response after eltrombopag withdrawal could be identified. Conclusion: Platelet response following eltrombopag cessation may be sustained in nearly half of adult patients with primary ITP after CR with eltrombopag. However, reliable markers for predicting which patients will have this response are lacking. Disclosures No relevant conflicts of interest to declare.

Background: Eltrombopag is an oral thrombopoietin receptor agonist (TPO-RA) drug approved in primary chronic ITP. Lack of clinical trials in secondary ITP avoids a clear demonstration of its potential in terms of safety and efficacy on secondary ITP. Aims: To evaluate the efficacy and safety of eltrombopag in secondary ITP patients in daily clinical practice in Spain. Methods: Ninety-eight secondary ITP patients (aged 18 years or more) from 30 Spanish centers, treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. Our study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: Our case series included 98 patients we allocated to four categories: immune disorders (n=47), infections (n=23), lymphoproliferative disorders (n=20), and neoplasms (n=8). The median age of the cohort was 62 (IQR, 40-71) years with 38 men and 60 women. At diagnosis, 34 patients had a Charlson Comorbidity Index score of 2 or more. Median time from ITP diagnosis to eltrombopag initiation was 13 (IQR, 2-66) months. Median number of therapies against thrombocytopenia before eltrombopag was 2 (IQR, 1-3), including rituximab (24), splenectomy (18) and romiplostim (13). Median platelet count when treatment started was 15 x 109/L (IQR, 5-43 x 109/L). Meanwhile, 44 patients had bleeding symptoms. Concomitant therapy was administered to 55 ITP (corticoids in 33) (Table I). Whole cohort eltrombopag response rate was 59% of responses (R; platelet count ≥30 x109/L and at least 2-fold increase the baseline count and absence of bleeding) with 52% of complete responses (CR; platelet count >100 x 109/L). Regarding the disease associated to ITP we observed high response rates in immune disorders and infection groups (67% of R, 76 % of R, respectively). Nevertheless, in lymphoproliferative disorders and neoplastic groups efficacy rates were much lower (36 % of R, 37 % of R respectively). The proportion of patients achieving platelet response was quite similar regardless the other studied parameters: age, sex, concomitant treatment, bleeding and platelet count at start of eltrombopag treatment. 30 adverse events were reported with eltrombopag, being 18 of them grade 3-4. 14 deaths were observed but only two were caused by bleeding. The remaining causes of death were: 4 because of bacterial sepsis and another 4 due to progression of basal disease. 2 secondary neoplasms, 1 aspergillosis and one death due to a non-treated severe anemia were also reported (Table II). Conclusion: The use of eltrombopag for treating secondary ITP is effective and safe. To point out, its efficacy in lymphoproliferative disorders and in neoplasm-associated ITP is lower than in benign diseases. Certainly, more studies are needed to confirm usefulness of TPO-RAs in secondary ITP cases. Table 1. Patient characteristics Variable Total(n = 98) Type of disease, n Immune disorders SLE 13 Evans Syndrome 8 Antiphospholipid Syndrome 6 Sjögren Syndrome 5 Rheumatoid Arthritis 3 Immunodeficiencies 3 Autoimmune Hepatitis 2 Primary Biliary Cirrhosis 2 Psoriatic arthritis 1 Evans Syndrome-Immunodeficiencies 1 Evans Syndrome-HCV 1 Graves-Basedow disease 1 Inflammatory Bowel disease 1 Lymphoproliferative disorders Lymphoproliferative diseases 16 HCV-Lymphoma 3 HIV-Lymphoma 1 Infections Hepatitis C Virus 16 HIV 5 HCV-HIV 2 Neoplasms Myeloid Neoplasms 8 Age, years, median [Q1;Q3] 62[40;71] Men/Women n 38/60 Bleeding at start of eltrombopag treatment, n 44 Concomitant treatment, n 55 Corticoids 33 Immunoglobulins 6 Corticoids and Immunoglobulins 7 Table 2. Adverse events with Eltrombopag Variable n Total, n 30 Serious Adverse Events (Grade 3-4), n 18 Progression of basal disease 4 Severe Bacterial Infections 3 Deep venous thrombosis 3 Stroke 2 Medullary fibrosis 2 Severe Bleeding 1 Aspergillosis 1 Pulmonary Embolism 1 Secondary neoplasms 1 Acute Pancreatitis 1 Acute Myocardial Infarction 1 Deaths, n 14 Bacterial Infections 4 Progression of basal disease 4 Secondary neoplasms 2 Severe Bleeding 2 Aspergillosis 1 Severe Anemia due to negative of patient to transfusion 1 Disclosures Off Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for secondary ITP patients..

Background SCORE understimates real Cardiovascualr Risk (CVR) in Rheumatoid ARtrhtis (1) and CVR in Psoriatic Arthritis (PsA) may be underestimated (2) too. The carotid intima-media thickness (CIMT) and the presence of atheroma plaques by Ultrasound (US) are significantly associated with risk for stroke or coronary heart disease (3) and translate a very high CVR Objectives To assess the CVR in PsA patients according to the SCORE chart, and the presence of subclinical vascular disease by US Methods Ongoing transversal descriptive study of PsA patients followed in our Rheumatology Division approved by the Ethic Committee of our Hospital. Clinical characteristics were recorded: age, gender, duration and type of disease, therapy; presence of classical CVR factors including body mass index (BMI), hypertension, dyslipidaemia, tobacco, and diabetes; personal and familiar cardiovascular events; lipid profile:total cholesterol (TC), high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) within the previous three months. CVR was calculated with SCORE calibrated for Spain (4). The patients underwent bilateral US carotid study with a GE LOGIQ S7 US Equipment. Billaterally the CIMT and the presence of atheroma plaques were assessed according to the Mannheim consensus (5). Patientes were reclassified upon US results. Results 40 patients included. Age was 55.8 years (SD 10.6) and 50% were female. Clinical characteristics are described in Table 1. The percentage of patients in the four levels of CVR (low, intermediate, high, and very high) was 0%, 67.5%, 25% and 7.5% respectively. 14 patients had plaques (35%), 13 (32.5%) were at the left side and 5 (12%) at the right side. In univariate analysis, plaques were associated with diabetes (P=0,005), hypertension (P=0,027) and age (P=0,039), but not with gender, dyslipidaemia, tobacco, neither length nor spectrum of the disease. 13 patients (32.5%) were reclassified and upgraded to very high risk. The final number of patients was 17 (42%), 8 (20%) and 15 (37.5%) for intermediate, high and very high risk respectively Conclusions The preliminary results of our patients with PsA show a substantial proportion of patients with a high or very high risk a priori of a fatal CV event. SCORE classification appears to underestimate the real CV risk done as 38% of patients have an estimated very high risk after the US study. These results, even in this short series, have relevant significance as most of the patients will require a specific therapeutic approach. References Peters MJ et al. EULAR evidenced-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis2010;69:325–31. Rosales JL et al. Cardiovascular risk assessment according to a national calibrated score risk index in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. J B Spine. 2014 Mar;:164-8. Lin YC et al. Relationship between metabolic syndrome and carotid intima-media thickness: cross-sectional comparison between psoriasis and psoriatic arthritis. Arthritis Care Res (Hoboken). 2014 jan;66(1):97-103. Sans S et al. Calibraciόn de la tabla SCORE del riesgo cardiovascular para Espana. Rev Esp Cardiol 2007;60:476–85. T ouboul PJ et al. Mannheim carotid intima-media thickness and plaque consensus. Cerebrovasc Dis. 2012;34:290-6. Disclosure of Interest None declared

Background Patients with chronic arthritis have a higher risk of cardiovascular (CV) events than the general population. Possibly this is due to both the high prevalence of classic cardiovascular risk factors (CVRF) and to the persistent inflammation due to their rheumatic disease. T2T approaches and other advances have increased our control of disease activity, however, classic CVRF are often monitored and treated exclusively by the GP. Objectives To describe the role of a nurse-clinic in the development of a specific program of patients with chronic inflammatory arthritides aimed at: 1) Detecting classic CVRF and 2) Optimizing the treatment of these classic CVRF Methods Following the EULAR 2010 recommendations, we developed a screening program for CVRF. Patients with the diagnosis of RA, SpA or PsA who were followed up at a single Rheumatology Department were offered participation in this program by their managing rheumatologist. In a single visit to a nurse-led clinic CV risk was evaluated through a clinical interview. Patients were asked about smoking status, diet, exercise, prior diagnosis of hypertension (HBP), diabetes (DM), dyslipemia (Dlp), personal and familial CV events, other comorbidities and their current treatment. Weight, height, BMI, and blood pressure were registered. Laboratory tests were then reviewed. SCORE tables were then applied and adjustment of the SCORE in RA patients was performed according to the EULAR recommendations. Those patients who did not achieve their target for the CVRF were sent to the rheumatologist for consultation. In the rheumatology nurse clinic, an educational program was initiated in order to modify diet, exercise, lifestyle and smoking cessation, where appropriate. The project is currently ongoing; preliminary results are presented. Results 63 patients (43 female) had been screened at the nurse-led clinic up to January 2015. Mean age was 58.6 years (SD 10.2). Diagnoses of the screened patients were 49 RA, 5 PsA and 9 SpA. At baseline, three patients had a history of CV events, 7 patients had a prior diagnosis of DM, 21 had HBP (13 with poor BP control), 16 had Dlp (5 with a total cholesterol >220mg/dL and 9 with an LDL-cholesterol higher than their therapeutic objective according to the SCORE estimation and European guidelines). 12 patients were active smokers and 24 were obese (BMI>30). In the patients without prior DM, the nurse clinic detected 3 patients (5/56, 5%) with glycemia ≥126mg/dL. In these patients a new blood test was ordered to confirm the diagnosis of DM. In patients without prior HBP 11 patients (11/42, 26%) had BP>140/90. In patients without prior Dlp 20 patients (20/47, 43%) had total cholesterol levels >220mg/dL and 21 (21/47, 45%) with LDL-cholesterol levels over their therapeutic target. Overall, this screening strategy allowed the detection of classical CVRF which were previously undetected or poorly controlled (DM, HBP, Dlp) in 43/63 (75%) of the evaluated patients. In all 63 patients, the nurse-led educational program was initiated. Conclusions A nurse led single-visit screening program allows the detection of classic CVRF in a high proportion of patients. If proper treatment for the classic CVF is initiated, this might result in a decrease of CV events with a favourable impact on the general health of chronic arthritis patients. Disclosure of Interest None declared

Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP. Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%. Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag. Disclosures No relevant conflicts of interest to declare.