Background Ankylosing Spondylitis (AS) typically affects young people, leading to progressive deterioration of physical function and quality of life (QoL) with higher use of healthcare services. Work disability and early retirement is also higher in AS patients than in the general population, with a remarkable negative impact on productivity and social costs. Objectives The objectives of this study were to assess the gradient of AS severity, measured by several well-established scores, for QoL, labour-market status and healthcare services demand, in a group of AS patients. Methods We collected cross-sectional data in patients under 65 years, concerning demographic characteristics, disease duration, time to diagnosis, BASDAI, BASFI, BASMI, SF-36, ASQoL, EQ-5D and evaluated the ASDAS. The number of appointments and emergency room visits during the year before and working status in active ages people, were also collected. To measure the gradient of AS on QoL scores, healthcare use and working status, regression models, with application of stepwise procedure for removal of statistically non-significant effects, were performed. Results A total of 369 patients were included (62.3% men and 37.1% women), with a mean age of 45.4±13.2 years (range 20–79 years). For SF-36 and ASQoL, only BASDAI and BASFI scores matter and both mean higher value associated with lower health and it seems that a one point increase in one score is roughly equal to one point increase in the other score. The same conclusion holds for EQ5D. The only difference lies with the group of patients with 7–12 years of schooling, who have higher utility score than the others. The probability of being employed is negatively related to age and to BASMI. Only the BASFI is positively associated with the number of medical appointments. Age and ASDAS are the only determinants of emergency rooms visits. Conclusions BASDAI and BASFAI, which are modifiable scores, are negatively associated with utility/ QoL scores. Age and BASMI (no modifiable scores) are negatively associated with being employed. In addition, earlier or later disease detection, have no influence on these gradients. Accuracy of therapy intervention has a pivotal role on impacts, more than a precise time in detection. Disclosure of Interest None declared

Background Approximately one-third of patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi) need to switch their biological therapy. However, a significant clinical response only occurs in half of switcher patients. Objectives To determine predictive factors of treatment response at 12 weeks in AS patients switching treatment to a second TNFi. Methods Patients with AS (1984 modified New York classification criteria) switching treatment to a second TNFi were identified in the Rheumatic Diseases Portuguese Register, Reuma.pt. Data was extracted at baseline (at second TNFi start) and at 12 weeks of follow-up. Variables included in the analysis were age, race, gender, BMI, education level, work status, tobacco and alcohol consumption, disease duration, time to diagnosis, peripheral arthritis, extra-articular manifestations, ESR, CRP, HLA-B27 positivity, previous DMARD and steroid therapy, BASDAI, ASDAS, BASFI, BASMI, first TNFi used, reason and time to switch. Univariable logistic regression analysis of baseline predictors of BASDAI response (improvement ≥2 units or ≥50%) was performed and variables with a p-value<0.25 were re-tested in multivariable regression models. Results Of the 334 AS patients treated with biologicals, 85 (25.4%) switched to a second TNFi. Reasons for switch included treatment failure (16; 18.8%), adverse events (25; 29.4%) and other reasons (44; 51.8%) like refractory extra-articular manifestations, surgery or patient preferences. Patients were included in the analysis if they stayed in therapy at least for 3 months and have BASDAI at baseline and at 3 months available. Forty-nine patients were analyzed, 22 responders (44.9%) and 27 non-responders (55.1%). BASDAI clinical response at 12 weeks was predicted by BASMI (p=0.04; OR 3.8 [95% CI 1.0, 14.1]) adjusting for gender, erythrocyte sedimentation rate and age at biological treatment onset. No other statistical significant demographical, clinical or laboratorial predictors were found. Conclusions We found 44.9% switchers who responded to the second TNFi. An increased BASMI score was an independent predictor of BASDAI clinical response to a second TNFi in AS patients. The inclusion of a greater number of patients in future studies may allow the determination of further predictive factors. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5590

Background Tumor necrosis factor-alpha inhibitors (TNFi) are currently the only therapeutic option when conventional treatment fails in ankylosing spondylitis (AS) patients. Objectives To assess the retention rate and investigate predictive factors and reasons for drug discontinuation in patients with AS starting their first TNFi. Methods We included all new biological starters AS patients fulfilling the 1984 modified New York classification criteria, registered at the Rheumatic Diseases Portuguese Register, Reuma.pt from June 2008 until October 2011. Retention rate at 2 years was evaluated using survival-data analysis methods with discontinuation of the drug, regardless the reason, as the primary outcome. Potential predictive factors of drug discontinuation (demographic, clinical and laboratorial) were assessed using log-rank tests and a Cox proportional-hazards regression model. Results Of the 334 AS patients starting a TNFi, 265 (79.34%) maintain treatment after 2 years of follow-up. Median drug survival among patients who discontinued treatment was 10.9 months (95% CI: 7.7 – 13.0 months) with a discontinuation rate of 11.6% per year. The main reason for treatment cessation was adverse events (34.4%) followed by lack of response at 12 weeks (23.2%). Drug survivals were similar regardless of the reason for discontinuation or TNFi used. Compared with patients who retain their first TNFi those who discontinue treatment, were more frequently women (p=0.04), were older at disease beginning (p=0.01) and at TNFi beginning (p=0.03), had higher BMI (p=0.01) and higher Bath Ankylosing Spondylitis Functional Index (BASFI, p=0.02) at baseline. In multivariable Cox regression, older age at TNFi beginning was the only baseline predictor of drug discontinuation (HR 1.06, 95% CI 1.02 – 1.10, p=0.006). Conclusions Retention rate was high among AS patients starting their first TNFi. Adverse events were the main reason for drug discontinuation and older age at treatment onset was a predictor of shorter drug survival. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3916

Human leukocyte antigen (HLA)-B27 is the mostly known major histocompatibility complex (MHC) gene associated with ankylosing spondylitis (AS). Nonetheless, there is substantial evidence that other MHC genes appear to be associated with the disease, although it has not yet been established whether these associations are driven by direct associations or by linkage disequilibrium (LD) mechanisms. We aimed to investigate the contributions of HLA class I and II alleles and B27-haplotypes for AS in a case-control study. A total of 188 HLA-B27 AS cases and 189 HLA-B27 healthy controls were selected and typed for HLA class I and II by the Luminex polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Allelic and haplotypic distributions were estimated by maximum likelihood method using Arlequin v3.11 and statistical analysis were performed by Stata10.1. No associations were found between non-HLA-B27 loci and AS susceptibility, but several associations were observed for phenotypic features of the disease. DRB1*08 was identified as a risk factor for uveitis and DQB1*04 seems to provide protection for AS severity (functional, metrological and radiological indexes). A*02/B27/C*02/DRB1*01/DQB1*05 [P<0.0001; odds ratio (OR) = 39.06; 95% confidence interval (CI) (2.34-651)] is the only haplotype that seems to confer susceptibility to AS. Moreover, the haplotype A*02/B27/C*01/DRB1*08/DQB1*04 seems to provide protection for disease functional and radiological repercussions. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 might play some role in AS susceptibility and severity.

Gold nanoparticles functionalized with thiol-oligonucleotides are ideal platforms for detection of specific DNA sequences. Here we evaluate the effect of single base mismatches in hybridization efficiency according to the position of the mismatch, base pairing combination and thiol-oligonucleotide density in terms of specificity and efficiency of target recognition. Hybridization efficiency and single-nucleotide polymorphism discrimination at room temperature is maximized at a density of 83 ± 4 thiol-oligonucleotides per 13.5 nm gold nanoparticle (24 pmol/cm2), and when the mismatch is localized at the 3′-end of the Au-nanoprobe, i.e. away from the gold nanoparticle surface.

To identify the cytokines that are present at higher levels in the serum and synovial fluid (SF) of patients with established rheumatoid arthritis (RA). Interleukin (IL)1β, IL2, IL4, IL6, IL8, IL10, IL12 (p70), IL17A, IL18, IL22, IL23, interferon (IFN)γ, leptin, MCP-1, MIP-1α, OPG, transforming growth factor β (TGFβ) and …

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly characterised by synovial hyperplasia and joint destruction. Although the aetiopathology of this autoimmune disease is not completely understood, it is known that it is associated with a misregulation of both the cellular immune system and the cytokine network. Nevertheless, little is known about the blood cytokine milieu in the first few weeks of RA. To determine …

The introduction of biological agents has provided a new therapeutic approach to the treatment of juvenile idiopathic arthritis (JIA).

The purpose of this study was to characterize the clinical and serological features of a large cohort of patients with antinuclear antibody (ANA) positive undifferentiated connective tissue disease (UCTD). Consecutive patients with UCTD, followed up at the Rheumatology Clinic of the participating centers, were included. Data from these patients were obtained by clinical evaluation and chart review. All patients were diagnosed as having UCTD on basis of the following criteria: positive ANA plus at least one clinical feature of connective tissue disease, but not fulfilling classification criteria for any differentiated connective tissue disease. One hundred eighty-four patients were studied (female patients—94.5%; mean age at time of evaluation—47 years). The most prevalent manifestations were arthralgia (66%), arthritis (32%), Raynaud’s phenomenon (30%), sicca symptoms (30%), and leukopenia (19%). The prevalence of ANA was 100%, anti-SSA 20%, anti-dsDNA 14%, and anti-SSB 7%. Patients with anti-dsDNA/anti-Sm, anticentromere/anti-Scl70, or anti-SSA/anti-SSB antibodies more frequently presented a set of manifestations close to systemic lupus erythematosus (SLE), systemic sclerosis, or Sjögren syndrome, respectively. We analyze a large cohort of UCTD. Seventy-two percent of these UCTD patients present lupus-, scleroderma-, or Sjögren-like features but do not fulfill classification criteria and mostly present a mild disease.

BACKGROUND Fracture risk assessment tools are useful to calculate the long term probability of osteoporotic fracture. However, how it reflects bone quality is unknown. The aim of this study was to correlate the WHO clinical fracture risk assessment tool, FRAX, with bone mechanical properties. METHODS Six patients submitted to hip replacement surgery, either due to osteoporotic fractures or to osteoarthritis, were evaluated. Bone samples were collected and the mechanical properties assessed by compression tests. Patients' data regarding the presence of clinical risk factors for fracture were registered. Laboratorial assessment of bone metabolic parameters and a dual X-ray absorptiometry(DXA) were done. RESULTS Analysis of the load-displacement curves showed that patients with fragility fractures (n=4) had low values of elastic modulus, yield load and energy absorbed until yield point. Osteoarthritis patients tend to have a better biomechanical performance.Femoral neck DXA scan was also performed in 3 patients. Fragility fracture patients had a lower bone mineral density than the patients with osteoarthritis. FRAX algorithm was applied and a positive relation was found between FRAX results and biomechanical parameters. Blood bone metabolic markers were within the normal range for all the subjects. CONCLUSIONS The worse mechanical properties observed in the fragility fracture patients were related to high probability of fracture given by FRAX. These observations, in a very small sample, need further confirmation. However, they suggest that the fracture risk assessment tool, FRAX, may reflect the current mechanical bone behavior of the patient.

OBJECTIVE:Association between ankylosing spondylitis (AS) and two genes, ERAP1 and IL23R, has recently been reported in North American and British populations. The population attributable risk fraction for ERAP1 in this study was 25%, and for IL23R, 9%. Confirmation of these findings to ERAP1 in other ethnic groups has not yet been demonstrated. We sought to test the association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to AS among a Portuguese population. We also investigated the role of these genes in clinical manifestations of AS, including age of symptom onset, the Bath Ankylosing Spondylitis Disease Activity, Metrology and Functional Indices, and the modified Stoke Ankylosing Spondylitis Spinal Score. METHODS:The study was conducted on 358 AS cases and 285 ethnically matched Portuguese healthy controls. AS was defined according to the modified New York Criteria. Genotyping of IL23R and ERAP1 allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests of genotypes as implemented in PLINK for dichotomous and quantitative variables respectively. A meta-analysis for Portuguese and previously published Spanish IL23R data was performed using the StatsDirect Statistical tools, by fixed and random effects models. RESULTS:A total of 14 nsSNPs markers (8 for IL23R, 5 for ERAP1, 1 for LN-PEP) were analysed. Three markers (2 for IL23R and 1 for ERAP1) showed significant single-locus disease associations, confirming that the association of these genes with AS in the Portuguese population. The strongest associated SNP in IL23R was rs1004819 (OR=1.4, p=0.0049), and in ERAP1 was rs30187 (OR=1.26, p=0.035). The population attributable risk fractions in the Portuguese population for these SNPs are 11% and 9.7% respectively. No association was seen with any SNP in LN-PEP, which flanks ERAP1 and was associated with AS in the British population. No association was seen with clinical manifestations of AS. CONCLUSION:These results show that IL23R and ERAP1 genes are also associated with susceptibility to AS in the Portuguese population, and that they contribute a significant proportion of the population risk for this disease.

Osteoporosis (OP) is defined as a systemic skeletal disease, characterized by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and, hence, susceptibility to fracture. Osteoporotic fractures, namely hip fractures, impose a major economic burden on healthcare systems. Globally, OP affects around 150 million people and in Europe it affects about 75 million persons. The Third National Health and Nutrition Examination Survey (NHANES III) study performed in United States of America, revealed that 20% of post-menopausal Caucasian women, 12% of Hispanic women and 8% of African American women, have OP. In Portugal, the incidence of hip fractures caused by low or moderate impact falls in women varies from 154 to 572 per 100 000 inhabitants, while in men the incidence is lower and varies from 77 to 232 per 100 000 inhabitants. Currently, the standard diagnostic tool for osteoporosis is Dual X-ray Absorptiometry (DXA) which only measures bone mineral density (BMD) and does not take into consideration the quality of bone, including its microarchitectural and structural design. The assessment of osteoporosis by BMD alo*Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon **Department of Rheumatology and Bone Metabolic Diseases, Hospital de Santa Maria, Lisbon ***Departamento de Engenharia de Materiais, Instituto Superior Técnico, Instituto de Ciência e Engenharia de Materiais e Superfícies, Lisbon ****Department of Orthopaedics, Hospital de Santa Maria, Lisbon Abstract