Search

Introduction: During the last decades, benzodiazepines (BZD) and antidepressants (ADP) have been among the most prescribed therapies in all developed countries. They have side effects, and BZD carry a risk of abuse and dependence disorders. The purpose of this study was to evaluate the prevalence of BZD and ADP among patients who attend a Rheumatology clinic, as well as the indication for these drugs. Methods: The study included patients who were referred for the first time to the Rheumatology clinic. Demographical data, reason for referral, and final diagnosis were recorded. The indication for ADP and/or BZD was recorded, as well as the duration of treatment. Sample size was estimated for a 0.05% alpha risk. Univariate and multivariate analyses were performed in order to study the relationships with the demographical or clinical characteristics. Results: A total of 350 patients were included (women 77.1%, men 22.9%). Most of them (73.4%) had been referred for musculoskeletal pain. More than a third (36.6%) of patients were on BZD and/or ADP. The most frequent reasons for their prescription were anxiety, depression, and insomnia. The final diagnosis in the clinic was a non-inflammatory condition in 82%, and an inflammatory one in 18%. In the univariate analyses, the use of BZD/ADP was associated with female gender (p

The AETHERA trial demonstrated that brentuximab vedotin (BV) consolidation after autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma (HL) at high risk of relapse/progression increases progression-free survival (PFS). Patients previously exposed to BV were excluded from that trial. However, BV alone or in combination with chemotherapy is frequently used as front-line treatment and/or pre-ASCT salvage therapy. We analyzed data from 156 patients with high-risk HL who underwent ASCT with (BV-CON, n = 62) or without (non-BV, n = 94) BV consolidation. Fifty-seven patients received BV-based salvage regimens before ASCT. The 3-year overall survival and PFS for all patients were 91.6% and 70.0%, respectively. Multivariate analysis showed that BV-CON was associated with better PFS (HR 0.39, p = 0.01), whereas positive PET at transplant leaded to worse PFS (HR 2.71, p = 0.001). BV-CON improved PFS in PET-positive patients (72.2% vs. 43.0%, p = 0.05), with a beneficial trend observed in PET negative (88.8% vs. 75.2%, p = 0.09). BV-CON patients with or without BV exposure pre-ASCT had a significantly better PFS than non-BV with or without BV pretransplant treatment (HR 0.36, p = 0.004). The efficacy of real-life BV consolidation therapy was similar to that in the AETHERA trial. This therapeutic strategy improves survival independently of BV exposure prior to ASCT.

espanolAims To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. Methods Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. Conclusions The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis. espanolObjetivos Describir la metodologia del Registro Espanol de Artritis Psoriasica de reciente comienzo de la Sociedad Espanola de Reumatologia (REAPSER), asi como sus fortalezas y limitaciones. El objetivo principal del proyecto es identificar factores pronosticos de la evolucion clinica y radiografica en una cohorte de pacientes que padecen artritis psoriasica (APs) diagnosticada con menos de 2 anos de evolucion. Material y metodo Estudio observacional, prospectivo (2 anos de seguimiento; periodicidad anual de las visitas), multicentrico. La intencion en la visita basal fue reflejar la situacion del paciente antes de que la evolucion de la enfermedad se viese modificada por los tratamientos pautados en los servicios de reumatologia. Los pacientes fueron invitados a participar consecutivamente en una de sus visitas habituales al reumatologo. El tamano muestral finalmente alcanzado fue de 211 pacientes. Se recogen datos sociodemograficos; de situacion laboral; historia familiar; antecedentes personales y comorbilidad; antropometricos; estilo de vida; uso de los servicios de salud; situacion clinica al diagnostico de APs; afectacion articular y dolor espinal; dolor y valoracion global de la enfermedad; entesitis, dactilitis y uveitis; afectacion cutanea y ungueal; situacion funcional y calidad de vida; evaluacion radiografica; determinaciones analiticas; tratamiento; brotes en esqueleto axial y periferico. Conclusiones El estudio REAPSER incluye una cohorte de pacientes con APs de inicio reciente reclutados antes de que la evolucion de la enfermedad se viese modificada por la prescripcion de FAME en los servicios de reumatologia. Se espera que la informacion exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros analisis.

Objective To identify factors associated with poor anticoagulation control with vitamin K antagonists (VKA) among outpatients with nonvalvular atrial fibrillation (NVAF) attended in Neurology and Internal Medicine in Spain. Methods Cross-sectional and multicenter study, from the ALADIN database, of outpatients with NVAF treated with VKA and attended in Internal Medicine and Neurology in Spain. Rates of anticoagulation control were determined with the direct and Rosendaal methods, considering data from the 6 months before the inclusion. Results Out of 1337 patients included in the ALADIN study, 750 were taking VKA, and complete information about INR values in the last 6 months was available in 383 patients. Mean scores of Charlson Index, CHADS2, CHA2DS2-VASc and HAS-BLED were 1.94 ± 1.54; 3.10 ± 1.26; 4.63 ± 1.54, and 2.20 ± 0.90, respectively. 46.2% and 47.0% of patients had an adequate anticoagulation control according to the direct and Rosendaal methods, respectively. Inadequate anticoagulation control according to the direct method was associated with diabetes (OR: 2.511; 95% CI: 1.144–5.659), prior labile INR (OR: 35.371; 95% CI: 15.058–83.083) and the determination of >6 INR controls in the last 6 months (OR: 4.747; 95% CI: 2.094–10.759), and according to the Rosendaal method, with prior labile INR (p Conclusions Despite the high thromboembolic risk, only a little more than a half of patients were well controlled. Factors associated with poor anticoagulation control were diabetes, labile INR, >6 INR controls and HAS-BLED.

Resumen Objetivo Identificar los factores asociados con el mal control de la anticoagulacion con antagonistas de la vitamina K (AVK) en pacientes con fibrilacion auricular no valvular (FANV) atendidos en consultas de Neurologia y Medicina Interna de Espana. Metodos Estudio transversal, multicentrico, anidado en el estudio ALADIN, de sujetos con FANV, tratados con AVK, atendidos en consultas de Medicina Interna o Neurologia de Espana. El grado de control de la anticoagulacion se estudio mediante el metodo directo y el de Rosendaal, considerando los 6 meses previos a la inclusion. Resultados De los 1.337 pacientes incluidos en ALADIN, 750 estaban tratados con AVK, con informacion completa sobre el INR de los ultimos 6 meses en 383 pacientes. Las puntuaciones medias del indice de Charlson, CHADS2, CHA2DS2-VASc y HAS-BLED fueron 1,94 ± 1,54; 3,10 ± 1,26; 4,63 ± 1,54 y 2,20 ± 0,90, respectivamente. El 46,2% y el 47,0% de los pacientes presentaban un control adecuado de la anticoagulacion por los metodos directo y Rosendaal, respectivamente. El control inadecuado de la anticoagulacion se asocio por el metodo directo con diabetes (OR: 2,511; IC 95%: 1,144-5,659), antecedentes de INR inestable (OR: 35,371; IC 95%: 15,058-83,083) y la realizacion de > 6 controles en los ultimos 6 meses (OR: 4,747; IC 95%: 2,094-10,759), y por el metodo de Rosendaal, con los antecedentes de INR inestable (p Conclusiones Pese al alto riesgo tromboembolico, solo estaban bien controlados algo mas de la mitad. Los factores asociados al mal control de la anticoagulacion fueron la diabetes, INR inestable, > 6 controles de INR y el HAS-BLED.

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.

Cardiovascular (CV) disease is the main cause of mortality in axial spondyloarthritis (axSpA). CV risk is enhanced by dysregulation of adipokines. Low omentin levels were associated with metabolic dysfunction and CV disease in conditions different from axSpA. Accordingly, we evaluated the genetic and functional implication of omentin in CV risk and subclinical atherosclerosis in a cohort of 385 axSpA patients. Subclinical atherosclerosis was evaluated by carotid ultrasound. Omentin rs12409609, in linkage disequilibrium with a polymorphism associated with CV risk, was genotyped in 385 patients and 84 controls. Serum omentin levels were also determined. omentin mRNA expression was assessed in a subgroup of individuals. Serum and mRNA omentin levels were lower in axSpA compared to controls. Low serum omentin levels were related to male sex, obesity, inflammatory bowel disease (IBD) and high atherogenic index. rs12409609 minor allele was associated with low omentin mRNA expression in axSpA. No association was observed with subclinical atherosclerosis at the genetic or functional level. In conclusion, in our study low omentin serum levels were associated with CV risk factors in axSpA. Furthermore, rs12409609 minor allele may be downregulating the expression of omentin. These data support a role of omentin as a CV risk biomarker in axSpA. We wish to thank all the patients and controls that participated in this study. This work was supported by funds of a NEXT-VAL grant (NVAL17/10) (Instituto de Investigación Sanitaria IDIVAL) awarded to FG. SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from the ‘Instituto de Salud Carlos III´ (ISCIII), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by the European Social Fund (ESF)). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the ESF (grant CP16/00033).

[Background]: Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65‐year‐old population., [Methods]: A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated., [Results]: Median age of our cohort was 76 (interquartile range, IQR, 70‐81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8‐21) days. Median time on response was 320 (IQR, 147‐526) days. Sixty‐three adverse events (AEs), mainly grade 1‐2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self‐limited pulmonary embolisms in secondary ITP were the only thrombotic events observed., [Conclusion]: Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD‐ITP were poor. A relatively high number of deaths were observed.

Background and objectives Immunosuppression is a known risk factor for cervical cancer. Women with rheumatic conditions are immunosuppressed due to the disease and the treatments. One of the main risk factors for this neoplasm is the lack of adherence to early detection programmes for human papillomavirus. The objectives of this study were to evaluate the adherence to the screening programme of patients in the Rheumatology Clinic, as well as to evaluate the prevalence of cervical lesions and their association with the different disease characteristics and the treatments received. Methods A descriptive retrospective study. The electronic medical history of patients actively being followed up in a tertiary hospital with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and systemic lupus erythematosus (SLE) were reviewed. Results Finally, 307 patients were included. No data were found for screening programme attendance in up to 42.4% of the patients (39.6% in RA, 43.8% in PSA and 46% in SLE). Among the patients who attended the screening programme at least once (57.6%), the prevalence of cervical dysplasia was 5.1%. No cases of neoplasia were found. In the simple logistic regression analysis, there was no association between attending the screening programme and any variable. The study also showed no association between the variables collected and the presence of infection and dysplasia. Conclusion These results are influenced by the absence of screening data in a significant percentage of patients and by the low prevalence of dysplasia found in this series of patients with rheumatic diseases.

Background Patients with autoimmune diseases suffer from an immunosuppressive state related to a pro-inflammatory environment and therapies received. Immunosuppression is a known risk factor for developing virus-associated cancers, including at uterine cervix (1,2). One of the major risk and prognostic factors for cervical neoplasm is missing the screening and early detection programs of human papilloma virus (HPV) (3). This screening is recommended for immunosuppressed women to be performed annually between 21 and 65 years of age (4). Objectives To audit the degree of adherence to HPV-cervical cancer screening of patients with chronic arthritis in the rheumatology unit of a tertiary center. Methods A descriptive, cross-sectional study was performed. The medical records of adult, female patients, with clinical diagnosis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), being followed in rheumatology clinics were reviewed. Assistance to screening clinics and cervical cytology and HPV-PCR results were revised to determine if patients had followed the screening program. Type of screening, number of visits and findings were also collected. A descriptive analysis is presented, with an estimate of the 95% confidence interval (95%CI) for the primary study variable. Results 233 medical histories (144 AR, 89 PsA) from patients with a median age of 55 years (p25-75 18-60) were included. Information related to the performance of cervical screening was found in the clinical records of 137 patients (58.8%, 95% CI 52.4-64.9%). Regarding the type of arthritis, the prevalence of performing cervical screening in RA and PsA was 60.4% and 56.2%, respectively, while rates of women attending the program at least twice were 45.1% for RA and 37.1% for PAs. In relation of screening findings, HPV infection was detected in 8 patients (5.8%), cervical dysplasia in 6 (4.4%), while no case of invasive cancer was detected. Conclusion Autoimmune and inflammatory diseases, along with the treatment employed, are associated with an increased risk of cervical HPV infection. Despite this, information regarding HPV cervical screening was collected in only half of patients. Both patients and their treating rheumatologists must be aware of this risk and adhere to cervical screening programs to achieve an early diagnosis and management. References [1] JAMA.2006;296:2823. 2) Int J Cancer.2013;132:1429. 3) Int J Cancer.2012;130:937. 4)Rev.Esp.Patol.2014;47(1):1-43. Disclosure of Interests None declared

Background There are scarce data regarding subclinical vascular disease in psoriatic arthritis (PsA)(1). Similarly to rheumatoid arthritis, the real CVR could also be underestimated by clinical risk charts (2). Objectives To study the prevalence of subclinical vascular atheromatosis in patients with PsA; to analyze the association of carotid plaques with PsA characteristics; to identify which patients with intermediate or high clinical risk would be worthwhile to undergo carotid ultrasound to detect plaque. Methods Descriptive, transversal and multicentric study, of patients with clinical diagnose of PsA followed in 4 Spanish hospitals. Demographic data, classic CVR factors and clinical characteristics were recorded. The probability of a 10 years fatal cardiovascular event was calculated by SCORE charts adapted for Spain (3), and afterwards a systematic bilateral common carotid ultrasound (4) was conducted. The intima-media thickness of the carotid wall and the presence of atheroma plaque were registered. Patient’s characteristics were described using descriptive analysis techniques. For univariate comparisons we used Chi2 and Anova. Multivariate analyses were conducted by logistic regression. The probability of plaque according to the age and the presence of CVR factors was calculated for patients with clinical intermediate or high risk by means of logistic regression. The study was approved by the Hospital General Universitario de Elda Ethic Committee (RCV-PS-MC/26/02/2016). Results 309 patients were included. The characteristics of the sample and the prevalence of CVR factors are depicted in Table 1. Patients were stratified by SCORE as follows: low risk 41 patients (13.3%), intermediate 182 (58.9%), high 75 (24.3%) and very high 11 (3.6%) patients. Plaque criteria by ultrasound was found in 95 patients (30.7%), who were reclassified as very high risk. Final distribution after carotid ultrasound showed a decrease in all groups (12%, 43.7% and 14.2% in low, intermediate and high risk, respectively) with a consequent increase in the very high risk group (30.1%). In the univariate study, plaque was associated with age (p 55 years (OR 2.84; IC 1.54-5.55), and with the number of classical CVR factors (OR 1.49; IC 1.13-1.97). In the presence of 3 or more risk factors, the probability of having plaque was 57.2% in patients with clinical intermediate risk and 61.8% in patients with high risk, and raised with increasing presence of CVR factors (Table 2). Conclusion Subclinical vascular disease is present in almost a third of the patients with PsA. SCORE tables may prove inaccurate for estimating the real CVR, and carotid ultrasound would be advisable in patients with intermediate or high risk who present any classical CVR factor. Disclosure of Interests None declared

Background Cardiovascular (CV) disease is one of the main causes of mortality in axial spondyloarthritis (axSpA). The higher incidence of CV risk factors and systemic chronic inflammation increase CV risk in axSpA.1 This is enhanced by a dysregulation of adipokines. Low levels of omentin, an anti-inflammatory adipokine, have been associated with metabolic dysfunction and CV disease in general population and conditions different from axSpA.2,3 Objectives To evaluate the implication of omentin in CV risk and subclinical atherosclerosis in axSpA at the genetic and functional (mRNA and protein) level. Methods 382 patients fulfilling the ASAS classification criteria for axSpA4 and 84 controls were included. Carotid ultrasound was performed to evaluate the presence of subclinical atherosclerosis. Serum omentin levels were assessed by ELISA. mRNA expression of ITLN1, coding omentin, was evaluated by RT-qPCR. ITLN1 rs12409609 (C/T), in complete linkage disequilibrium with a polymorphism previously associated with coronary artery disease,5 was genotyped by TaqMan probes. Results were adjusted by potential confounding factors (STATA® v.11.1). Results Serum and mRNA levels of omentin were lower in axSpA compared to controls (p Conclusion style=”font-family: ‘Times New Roman’,’serif’; font-size: 10.0pt; margin: 0cm; margin-bottom: 8.0pt; line-height: 106%; margin-left: 0cm; margin-right: 0cm; margin-top: 0cm; mso-style-name: Normal_0; text-align: justify;” fontsize=”11.0” data-pos-index=”15” class-name=”Deleted”>Omentin is linked to obesity and adverse lipid profiles in axSpA. Additionally, low serum levels of omentin are associated with the presence of IBD in axSpA. These data support a role of omentin as a CV risk biomarker in axSpA. References [1] Joint Bone Spine.2014;81:57-63. [2] Cardiovasc Hematol Disord Drug Targets.2013;13:59-72. [3] Curr Issues Pharm Med Sci.2015;28:176-80. [4] Ann Rheum Dis.2009;68:777-83. [5] Asian Cardiovasc Thorac Ann.2017;25:199-203. Acknowledgement Study supported by NVAL17/10 (IDIVAL). Personal funds: FG: Sara Borrell fellowship CD15/00095 (ISCIII-ESF); SR-M: RD16/0012/0009 (ISCIII-ERDF); VP-C: PREVAL18/01 (IDIVAL); VM and RL-M: Miguel Servet type I CP16/00033 (ISCIII-ERDF, ISCIII-ESF). Disclosure of Interests Fernanda Genre: None declared, Javier Rueda-Gotor: None declared, Sara Remuzgo-Martinez: None declared, Veronica Pulito-Cueto: None declared, Alfonso Corrales: None declared, Veronica Mijares: None declared, Leticia Lera-Gomez: None declared, Virginia Portilla: None declared, Rosa Exposito: None declared, Cristina Mata: None declared, Ivan Ferraz-Amaro: None declared, Vanessa Hernandez-Hernandez: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Esther Vicente: None declared, Cristina Fernandez-Carballido: None declared, Maria Paz Martinez-Vidal: None declared, David Castro-Corredor: None declared, Joaquin Anino-Fernandez: None declared, Juan Carlos Quevedo-Abeledo: None declared, Carlos Rodriguez-Lozano: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Oreste Gualillo: None declared, Javier Martin Ibanez: None declared, Javier Llorca: None declared, Raquel Lopez-Mejias: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi.

Background Treatment with rituximab (RTX) for rheumatologic diseases may produce hypogammaglobulinemia (hypoglb) (1,2), and that way increase the risk to acquire certain infections (3,4). There are no stablished guides to evaluate and treat hypoglb in these patients. In our hospital, the percentage of patients who develop hypoglb and severe infections is unknown. Objectives To analyse the effect of RTX on immunoglobulin (Ig) levels and to evaluate the severe infections and hepatitis B reactivations that could be related to this treatment. Methods This is a descriptive, retrospective study of patients followed up in the Rheumatology Unit of the Alicante General University Hospital (HGUA) who had received at least one course of RTX. Clinical characteristics and laboratory parameters were obtained from the electronic charts: type of disease, posology and total amount of RTX, Ig levels before and after treatment with RTX, the concomitant treatment with disease-modifying drugs (DMDs), hepatitis B virus’s (HBV) reactivations and infections that required hospitalization. Hypoglb was assessed when IgG Results Finally 106 patients were included, 85 women (80.2%) and 21 men (19.8%). The more frequent conditions were rheumatoid arthritis (47.2%), Sjogren syndrome (16%), Systemic Lupus Eritematosus (13.2%), vasculitis (6.6%) and other connective tissue diseases (10.4%). Characteristics of the sample are shown in table 1. A correct follow up of the Ig levels during the treatment was shown to be undergone in 87.7% of the cases. It was found that 35.8% of the patients presented hypoglb and 13,2% presented severe infections after receiving RTX. No HBV reactivations were found. Among the patients with hypoglb, 78.9% received concomitant treatment with other immunosuppressants (methotrexate 23.6%, leflunomide 23.6%). Hypoglb was more frequent in rheumatoid arthritis (44%), lupus (42.8%) and vasculitis (28.6%). Through simple logistic regression hypoglb during treatment was associated with the presence of previous hypoglb (p=0.025), higher doses received (p=0.01) and longer treatment (p=0.003). In the multiple logistic regression, only low levels of Ig before treatment turned out to be an independent risk factor for hypoglb during treatment (OR 6.86; IC 1.25-37.57). The IgM and IgA levels, but no the IgG levels were significantly lower in patients who has severe infections. Conclusion Hypogammaglobulinemia happens in a third of the patients who receive RTX, especially in those who have low previous IgG levels; therefore a follow up during the treatment should be encouraged. Low IgM and IgA levels during the treatment could also be associated with severe infections. References [1] Christou EAA. Int Rev Immunol. 2017;3:352. [2] Roberts DM. Journal of Autoimmunity 2015;57:60 [3] Gea-Banacloche, JC; Seminars in Hematology 2010;47:187. [4] Salliot C.Ann Rheum Dis 2009;68:25 Disclosure of Interests Andres Fierro: None declared, Mariano Andres: None declared, Jenny de la Torre-Aboki: None declared, Paloma Vela-Casasempere Grant/research support from: UCB, Abbvie, Pfizer, Roche, Bristol-Myer-Squibb (another research, not BIOBADASER related), Consultant for: UCB, Lilly, Pfizer, Roche, Bristol-Myer-Squibb, Speakers bureau: Roche, UCB, MSD, Pfizer, GSK, BMS, Lilly, Maria Paz Martinez-Vidal: None declared

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.

[Introduction]: Molecular testing of Inherited bleeding coagulation disorders (IBCDs) not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and in certain cases genotype–phenotype correlations are important for predicting the clinical course of the disease and to allow tailor-made follow-up of individuals. Until recently, genotyping has been mainly performed by Sanger sequencing, a technique known to be time consuming and expensive. Currently, next-generation sequencing (NGS) offers a new potential approach that enables the simultaneous investigation of multiple genes at manageable cost. [Aim]: The aim of this study was to design and to analyse the applicability of a 23-gene NGS panel in the molecular diagnosis of patients with IBCDs. [Methods]: A custom target enrichment library was designed to capture 31 genes known to be associated with IBCDs. Probes were generated for 296 targets to cover 86.3 kb regions (all exons and flanking regions) of these genes. Twenty patients with an IBCDs phenotype were studied using NGS technology. [Results]: In all patients, our NGS approach detected causative mutations. Twenty-one pathogenic variants were found; while most of them were missense (18), three deletions were also identified. Six novel mutations affecting F8, FGA, F11, F10 and VWF genes, and 15 previously reported variants were detected. NGS and Sanger sequencing were 100% concordant. Conclusion: Our results demonstrate that this approach could be an accurate, reproducible and reliable tool in the rapid genetic diagnosis of IBCDs.

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

Aims: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. Methods: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. Conclusions: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis. (C) 2018 Elsevier Espafia, S.L.U. and Sociedad Espailola de Reumatologia y Colegio Mexicano de Reumatologia. All rights reserved.

42 p.-8 fig., Drug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs against Leishmania share this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in Leishmania were poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline on Leishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insight into the sertraline effects on bioenergetics metabolism of the parasite. Sertraline induced respiration uncoupling, a significant decrease of intracellular ATP level, and oxidative stress in L. infantum promastigotes. Metabolomics evidenced an extended metabolic disarray caused by sertraline. This encompasses a remarkable variation of the levels of thiol-redox and polyamine biosynthetic intermediates, as well as shortage of intracellular amino acids used as metabolic fuel by Leishmania Sertraline killed Leishmania through a multitarget mechanism of action, tackling essential metabolic pathways of the parasite. As such, sertraline is a valuable candidate for visceral leishmaniasis treatment under a drug repurposing strategy., This work was supported by grants of the Fondo de Investigaciones Sanitarias-ISCIII-FEDER (PI12-02706), and (RD16/0027/0010, Red de Enfermedades Tropicales, subprogram RETICS del Plan Estatal de I+D+i (2013-2016) co-financed with FEDER funds, SAF2015-65740-R, and CSIC PIE 201620E038 to L. R., São Paulo State Research Foundation (FAPESP 2015/23403-9 to A. G.T.); EADS-CASA/ Brazilian Air Force (FAB) mobility program to M.L.L., and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) to M.L.L.

Background Osteoporosis (OP) and vertebral fractures (VF) are common comorbidities of axial Spondyloarthritis (axSpA) with deleterious effects for the physical function of the patients. Objectives To evaluate the relationship between disease activity and radiographic damage and bone mineral density (BMD), 25 (OH) vitamin D levels and VF in patients with axSpA (ASAS Criteria). Methods Cross-sectional study. Activity variables: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS); ESR and CRP. Vitamin D insufficiency if Results We studied 206 patients (62 women/144 men); 86% AS/14% nr-axSpA and associated peripheral involvement in 42%. Mean ±standard deviation (SD) values: age 52±14; activity (BASDAI 3.6±2.2, ASDAS-CRP 2.2±0.95, ASDAS-ESR 2.5±0.99, CRP 4.97±8.97 mg/L, ESR 18.2±14, 8 mm); physical function (BASFI 3.3±2.7); radiographic damage: mSASSS total 20.46±19.14, lumbar 10.41±9.89 and cervical 10.05±10.78; 25 (OH)vitD 19.83±9.25 ng/mL, 85.7% of the patients had insufficiency. Low LS BMD in 25.7% (z-score) and 28.9% (t-score) and low FN BMD in 45.2% (z) and 28.9% (t) of the patients. OP prevalence in LS 3.2%(z)/6.9%(t) and in FN 9.1% (z)/13.4% (t). Morphometric VF were identified in 34% of the patients. Bivariate analysis: ESR, ASDAS-ESR, age, male sex, low 25 (OH) vitD levels and the mSASSS were associated with low FN BMD. Multivariate models confirmed the association between disease activity (ASDAS-ESR) [OR 3.32 (95% CI: 2.35 to 4.55); p=0.016], 25(OH)D [OR 0.95 (95% CI: 0.86 to 0.98); p=0.029] and low FN BMD (z score). An association was confirmed between CRP [OR 2.34 (95% CI: 1.10 to 4.98); p=0.027], radiographic damage [lumbar mSASSS OR 1.06 (95% CI: 1.03 to 1.10) p=0.001], high LS BMD [OR 296 (95% CI: 5.07 to 12258); p=0.006] and low FN BMD [OR 0.11 (95% CI: 0.03 to 0.12); p=0.000] and the presence of VF. Conclusions In patients with axSpA, low FN BMD is associated with disease activity and vitamin D insufficiency and VF are associated with CRP and low hip bone mass. Furthermore, the presence of radiographic damage, even when ‘falsely’ increases LS BMD, is associated with the presence of fractures. Reference [1] Van der Heide, et al. 2016update of the ASAS-EULAR management recommendations of axial SpA. Ann Rheum Dis2017 Jun;76(6):978–991. Disclosure of Interest None declared

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 109/l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 109/l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients 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 months, with 4/26 having ITP

To substantiate the functionality of a crystallographically evidenced allosteric site in Bacillus caldovelox arginase (Bewley et al., 1999), we have examined the kinetic consequences of the single mutations of Asp199 and Glu256, which interact with l -arginine in this site. The introduced mutations (Asp199 → Asn, Asp199 → Ala, Glu256 → Gln and Glu256 → Ala) had no effect on the hexameric structure of the enzyme (mol. wt. 195 ± 10 kDa). However, in contrast with the Michaelis–Menten kinetics exhibited by the wild-type species, the D199A, D199N, E256A and E256Q variants exhibited positive cooperativity with respect to l -arginine. The Glu278 → Ala mutation, which compromise interactions at the trimer–trimer interface, yielded trimeric species (mol. wt. 100 ± 5 kDa) exhibiting hyperbolic kinetics that changed to sigmoidal by the additional Glu256 → Ala mutation. In addition to demonstrating the total functionality of the trimer, our results also suggest that B. caldovelox is kinetically cooperative and that the commonly detected hyperbolic behavior results from binding of l -arginine as a typical allosteric activator.

Objectives To analyse the cardiovascular risk according to the SCORE chart in a series of patients with psoriatic arthritis, and to study the presence of subclinical cardiovascular disease by carotid ultrasound. Methods Cross-sectional descriptive study of patients with psoriatic arthritis attended in a tertiary hospital. The presence of classical cardiovascular risk factors and the clinical characteristics of the patients were recorded. The cardiovascular risk was calculated with SCORE, calibrated for Spain. Common carotid ultrasound was conducted to assess intima-media thickness and the presence of atheroma plaques. Patients were reclassified upon ultrasound results. Statistical analyses were made for sample description, and multivariate analyses were performed to investigate the associations with the presence of atheroma plaques. Results A total of 102 patients were included. According to SCORE charts, 70.6% of the patients had intermediate cardiovascular risk, 25.5% high risk and 3.9% very high risk. After the ultrasound study, 26.5% of the patients were upgraded, and reclassified as very high risk due to the presence of plaques. The presence of subclinical vascular disease was associated with higher uric acid levels ( P = 0.036) and the presence of 2 or more cardiovascular risk factors ( P = 0.021). Conclusions A considerable number of psoriatic arthritis patients have a priori moderate or high risk of a fatal cardiovascular event. Carotid ultrasound detects subclinical vascular disease and increases the real risk in a substantial proportion of patients. Cardiovascular risk prediction clinical tools such as the SCORE underestimate the presence of subclinical cardiovascular disease in patients with psoriatic arthritis.

Multifunctional nanoparticles are usually produced by sequential synthesis, with long multistep protocols. Our study reports a generic modular strategy for the parallel one-step multifunctionalization of different hydrophobic nanoparticles. The method was designed and developed by taking advantage of the natural noncovalent interactions between the fatty acid binding sites of the bovine serum albumin (BSA) and the aliphatic surfactants on different inorganic nanomaterials. As a general example of the approach, three different nanoparticles-iron oxide, upconverting nanophosphors, and gold nanospheres-were nanoemulsified in water with BSA. To support specific applications, multifunctional capability was incorporated with a variety of previously modified BSA modules. These modules include different conjugated groups, such as chelating agents for (68)Ga or (89)Zr and ligand molecules for enhanced in vivo targeting. A large library of 13 multimodal contrast agents was developed with this convergent strategy. This platform allows a highly versatile and easy tailoring option for efficient incorporation of functional groups. Finally, as demonstration of this versatility, a bimodal (PET/MRI) probe including a maleimide-conjugated BSA was selectively synthesized with an RGD peptide for in vivo imaging detection of tumor angiogenesis.

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.

SummaryThe diagnosis of von Willebrand disease (VWD) remains difficult in a significant proportion of patients. A Spanish multicentre study investigated a cohort of 556 patients from 330 families who were analysed centrally. VWD was confirmed in 480. Next generation sequencing (NGS) of the whole coding VWF was carried out in all recruited patients, compared with the phenotype, and a final diagnosis established. A total of 238 different VWF mutations were found, 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 463 were found to have VWF mutation/s. A good phenotypic/ genotypic association was estimated in 96.5 % of the patients. One hundred seventy-four patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred sixteen patients presented with mutations that had previously been associated with increased von Willebrand factor (VWF) clearance. RIPA unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 70 patients. The NGS study facilitated an appropriate classification in 63 of them. The remaining seven patients presented with a VWF novel mutation pending further investigation. In five patients with a type 3 and two with a type 2A or 2B phenotype with no mutation, an acquired von Willebrand syndrome (AVWS) was suspected/confirmed. These data seem to support NGS as a first line efficient and faster paradigm in VWD diagnosis.Supplementary Material to this article is available online at www.thrombosis-online.com.

Lipids are important components of biological systems, and their role can be currently investigated by the application of untargeted, holistic approaches such as metabolomics and lipidomics. Acquired data are analyzed to find significant signals responsible for the differentiation between the investigated conditions. Subsequently, identification has to be performed to bring biological meaning to the obtained results. Lipid identification seems to be relatively easy due to the known characteristic fragments; however, the large number of structural isomers and the formation of different adducts makes it challenging and at risk of misidentification. The inspection of data, acquired for plasma samples by a standard metabolic fingerprinting method, revealed multisignal formations for phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins by the formation of ions such as [M + H](+), [M + Na](+), and [M + K](+) in positive ionization mode and [M - H](-), [M + HCOO](-), and [M + Cl](-) in negative mode. Moreover, sodium formate cluster formation was found for [M + H·HCOONa](+) and [H-H·HCOONa](-). The MS/MS spectrum obtained for each of the multi-ions revealed significant differences in the fragmentation, which were confirmed by the analysis of the samples in two independent research centers. After the inspection of an acquired spectra, a list of characteristic and diagnostic fragments was proposed that allowed for easy, quick, and robust lipid identification that provides information about the headgroup, formed adduct, and fatty acyl composition. This ensures successful identification, which is of great importance for the contextualization of data and results validation.

The correct diagnosis and classification of von Willebrand disease (VWD) is difficult because of the variability of its clinical expression and limitations of laboratory methods. However, correctly diagnosing VWD is important for therapy and genetic counselling. A survey related to the referred VWD patients in Spain revealed local diagnostic problems in at least one third of the cases of VWD. Consequently, a Spanish multicenter study was carried out in which a cohort of 556 patients from 330 families was analyzed centrally. VWD was confirmed in 480 patients. Next generation sequencing (NGS) of the whole coding von Willebrand factor gene ( VWF ) was carried out in all recruited patients, compared with the phenotype, and a final diagnosis was established. A total of 238 different VWF mutations were found: 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 467 were found to have a VWF mutation/s. A good phenotype/genotype association was estimated in 94.6% of the cases. One hundred and eighty patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred and sixteen patients presented with mutations that had previously been associated with an increased VWF clearance. Ristocetin induced platelet agglutination (RIPA) unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 74 patients. A local/central disagreement over diagnosis occurred in 42.3% of the whole cohort. The NGS study facilitated an appropriate classification in 60 of them. Based on these results, a proposal for a change in the VWD diagnostic paradigm, suggesting the inclusion of the analysis of VWF at the initial diagnostic process, has been made. An extension of this project to include 400 new VWD patients has begun. A diagnostic strategy has been developed, and a Spanish consensus guideline for optimal treatment of VWD was developed in Spain. Desmopressin (DDAVP) is the treatment of choice in responsive VWD patients. VWF concentrates (VWF/FVIII) are used in individuals unresponsive to DDAVP, when DDAVP is contraindicated, or in VWD types 2B and 3, and for long term management needs (e.g., post major surgery).