BackgroundThe management of comorbidity in patients with axial spondyloarthritis (Ax-SpA) needs improvement; the implementation of clinical practice guidelines is still deficient and heterogeneous.ObjectivesTo prioritise comorbidities in Ax-SpA and to elaborate practical aids for their identification and follow-up.MethodsA multidisciplinary panel [10 rheumatologists (6 experts in Ax-SpA), 2 family doctors, 1 internist, 1 cardiologist, 1 gastroenterologist, 1 psychologist and 3 methodologists] prioritised, in a discussion group, a list of comorbidities based on frequency and impact. Each comorbidity was discussed largely and systematic reviews were performed to support or discard items. In a second meeting, items to be included were presented, discussed, and those with lower priority disregarded.ResultsThe panel produced a checklist for health professionals and another for patients. Each item is supported by arguments and references. Table 1 shows, schematically, the items included in the checklists.Table 1.Items included in the checklistUsual treatmentOf note: oral anticoagulants, antihypertensive drugs, ASA, steroids and NSAIDs. Specific comorbiditiesHypertension, heart failure, renal failure, liver cirrhosis, gastric ulcer, infections, tuberculosis, neurological disease, and fracture risk.Vaccine schedule and dental hygienePatient's vaccination status; prevention of infections.Life-stylePhysical activity (amount and type).Alcohol consumption. Detect possible abuses; important risk factor for other comorbidities.Depression, quality of sleep and sexual lifeThe impact of Ax-SpA in the psychosocial sphere is relevant and should be carefully evaluated. Specific questionnaires are recommended.Non-preventable diseasesFrequent association with uveitis, inflammatory bowel disease and cardiac pathology; systematise questionsConclusionsThese checklists are intended to facilitate the systematic evaluation of co-morbidity associated with Ax-SpA, thus allowing an earlier detection and better control and management of these patients by the rheumatologist.AcknowledgementsThis project was funded by Merck Sharp & Dohme Spain. Merck Sharp & Dohme had no influence on either the development of the project or the final content of the abstract.Disclosure of InterestNone declared
BackgroundDuring the development of recommendations and implementation aids of the GECOAx project, the importance of avoiding certain situations was highlighted.ObjectivesTo recognize what prescriptions, risk assessments, or preventive strategies are wrong practices and should thus be avoided in clinical practice. To establish not to do recommendations in the management of the comorbidity of AxSpA.MethodsA multidisciplinary group was selected [10 rheumatologists, 1 internist, 1 cardiologist, 1 gastroenterologist, 1 psychologist and 2 family physicians]. With the support of 3 methodologists, and after interactions aimed to edit a document for the management of comorbidity launched by the same panel, a list of Not to do recommendations was issued. In a discussion meeting, evidence was provided to support the recommendations, items without sufficient basis were removed, and the final list was produced.ResultsA summary list of Not to do recommendations (Table 1) was issued.Table 1– DO NOT prescribe NSAIDs to patients with high cardiovascular (CV) risk and particularly with hypertension.– DO NOT prescribe NSAIDs to patients with CKD, heart failure or liver cirrhosis and, if necessary, exert caution.– DO NOT use CV risk scores in patients who already suffered a CV event or those with multiple risk factors (smoking, obesity, sedentary lifestyle, DM, hypertension, dyslipidemia) or a family history of premature CV disease; All should be considered high CV risk.– DO NOT base renal disease screening on a single glomerular filtration test and/or albuminuria (ALWAYS should be confirmed); serum creatinine should not be used as the only test to evaluate renal function.– DO NOT administer biological therapy in case of active, serious and uncontrolled infection, sepsis or risk of sepsis or tuberculosis or without a previous screening of chronic HBV, HCV, HIV and TB.– DO NOT repeat HBV vaccination unless HBV antibody levels are not achieved.– DO NOT vaccinate a patient in therapy with biological agents or in immunosuppressive treatment with live virusesConclusionsThese recommendations aim to avoid making common mistakes in clinical practice and to help better management of frequent comorbidity in patients with AxSpA.AcknowledgementsThis project was funded by Merck Sharp & Dohme Spain. Merck Sharp & Dohme had no influence on either the development of the project or the final content of the manuscript.Disclosure of InterestNone declared
Background Psoriatic Arthritis (PsA) is a complex disease and is present in ∼11% in patients with Psoriasis (Ps). Recently, Genomewide Association Studies (GWAS) have expanded the number of risk loci for Ps in >20 new loci. Two of these genes, ERAP-1 and HLA-C, have been shown to interact epistatically in the risk to develop Ps. Objectives We have studied the presence of new genetic interactions between Ps risk lci with the HLA region in Purely cutaneous Psoriasis (PsC) and PsA. Methods Within each Ps risk locus (n=31), the SNP having the highest statistical evidence was selected. The 31 SNPs were genotyped using Taqman technology in a cohort of n=955 PsA, 1,050 PsC and 1,497 hypernormal controls of the Spanish population. The presence of statistically significant gene-gene interactions was performed using a logistic regression model with three parameters to determine the presence of interaction at the allelic level. Results We replicated the previously described interaction of HLA-C and ERAP1 in the PsC cohort but not in the PsA cohort. We identified, for the first time, a significative epistatic association between HLA-C and SERPINB8. Microarray gene expression studies on cutaneous biopsies corroborate the presence of this interaction at a functional level. In PsA, no statistically significant interactions where identified with variation at HLA-C. However, 6 of the studied genes showed a significant (P<0.05) association with HLA-B27 positivity. Conclusions The present study has identified new genetic interactions associated with the risk to develop PsC and PsA. The functional study of these interactions will improve our knowledge of the biological basis of these complex diseases. Disclosure of Interest None Declared
BackgroundPsA has a higher heritability than PsV, indicating the existence of additional PsA-specific genetic factors. To date, however, the specific genetic basis underlying PsA is poorly understood.ObjectivesThe objective the present study was to identify new genetic variation specifically associated with PsA risk.MethodsIn order to characterize the genetic basis of PsA, we performed a GWAS meta-analysis at the single-marker level as well as at the pathway level (GWPA). A cohort of 835 PsA patients and 1,558 controls from the Spanish population was genotyped for >550,000 SNPs. GWAS data from a second cohort of 1,430 PsA patients and 1,417 controls from the North American population was also used. In order to confirm the specificity of the new genetic variation associated with PsA risk, we analyzed the association with purely cutaneous psoriasis (PsC, n=614) and rheumatoid arthritis (RA, n=1,191). We performed a pharmacogenetic analysis to investigate the new PsA-specific pathways as a source for drug discovery in PsA.ResultsGWAS meta-analysis identified a new association between B3GNT2 gene and PsA (P<5e-08). In the GWAS pathway analysis, we identified and validated a total of 14 genetic pathways associated with PsA risk. From these, the glycosaminoglycan (GAG) metabolism pathway was also found to be significantly associated with PsA risk when directly contrasted to the PsC cohort as well as the RA cohort. At the functional level, we detected a significant differential expression of GAG metabolism pathway genes in blood samples from PsA patients compared to PsC patients. The pharmacogenetic analysis identified several FDA-approved drugs likely to modify the GAG pathway.ConclusionsThe present study represents an important step towards the characterization of the genetic factors specific to PsA risk.Disclosure of InterestNone declared
BackgroundPsoriatic Arthritis (PsA) is a complex disease of unknown etiology, involving both genetic and environmental factors.ObjectivesTo analyze the more relevant epidemiological characteristics in a large cohort of patients with PsA and controls in the Spanish population.MethodsA cross-sectional, comparative, multicenter study of patients with PsA and hypernormal healthy subjects for IMID diseases was performed. All patients were recruited through the Immune-Mediated Inflammatory Diseases Consortium (IMIDC).The IMIDC is a network of Spanish biomedical researchers focused in the study of the molecular basis of immune-mediated inflammatory diseases. All patients included in the present study were selected from the outpatient clinics of 13 Rheumatology Departments at different Spanish University Hospitals. An epidemiological questionnaire developed by experts at DNA National Bank was applied to obtain all data.Results1,602 PsA patients and 1,558 healthy subjects were included. 53% of PsA patients and 60% of controls were male. The mean age of patients PsA patients and controls was 52±13 years and 49±7 years respectively. In the univariate analysis, we observed that the height and weight of the control subjects was significantly higher than in patients with PsA.The level of statistical significance was decreased by introducing gender and age as covariates.In our cohort,55% of patients with PsA had no education or only primary education. Control subjects mostly had secondary or higher education.The physical exercise was significantly more frequent among controls. The gender and age affect the assessment of physical activity performed by both groups of patients.Regarding employment status, most patients with PsA (29%) and controls (44%) were external employers.Both PsA patients and controls (52%) most frequently use their private cars.The mean consumption of tobacco and alcohol was higher in the control group and the statistical significance was maintained in multivariate analysis.In both univariate and multivariate analysis,statistical differences in the average number of children and consumption of coffee were observed.ConclusionsIn this large comparative study we describe for the first time the general epidemiological characteristics in patients with PsA and healthy subjects representative of the Spanish population.PsA patients are older, have an average number of children higher and lower consumption of alcohol and tobacco than controls. The influence of gender confirms the significance level of variables such as physical activity, weight and height.Disclosure of InterestNone declared
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