A Rodrigues

Evolution of the North Portuguese coast in the last 18,000 years

Abstract At the maximum of the last glacial (18 ka BP) the polar front was situated between 37° and 40° N in the vicinity of the Portuguese continental margin. General warming of the atmosphere (which began 16 ka BP) was responsible for the progressive northward retreat of the polar front and for the subsequent rise in mean sea level (Pujel, 1980; Ruddiman and McIntyre, 1981). Morphological and sedimentological studies have been used to trace the evolution of the coastline since the last glacial maximum. An erosive surface underlying the unconsolidated sedimentary cover has been identified along the Portuguese shelf and is considered to have formed at the last glacial maximum when this area was exposed. In the present work this surface has been investigated using light seismic reflection. Identification of morphological elements of coastal origin, together with mapping of surficial sediments (relict palimpsest and amphoteric deposits) has allowed the reconstruction of the coastline during the post-glacial migration, from the lowest stand to the present.

Bilateral Evaluation of the Hand and Wrist in Untreated Early Inflammatory Arthritis: A Comparative Study of Ultrasonography and Magnetic Resonance Imaging

Objective. To compare Doppler ultrasound (US) and 3.0-Tesla magnetic resonance imaging (3.0-T MRI) findings of synovial inflammation in the tendons and joints in an early polyarthritis cohort (patients who presented < 1 year after arthritis onset) using a bilateral hand and wrist evaluation. Also, to evaluate the diagnostic performance of US and MRI findings for rheumatoid arthritis (RA), their ability to predict RA as a diagnostic outcome, and their capacity to improve the accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria in early arthritis. Methods. Forty-five patients (40 women, 5 men; mean age 45.6 yrs) with untreated recent-onset polyarthritis participated in this prospective study and were examined using an US and MRI approach including both wrists and hands. After a followup of 12 months, patients were classified as having RA if they fulfilled the criteria for RA. The proportion of synovitis identified by US and MRI for each joint and tendon region was compared by chi-square test. The diagnostic performance of US and MRI for RA identification was evaluated using receiver-operating curve (ROC) analysis. Possible associations between synovitis for each joint and tendon region as identified by US or MRI and RA diagnosis at 12 months were tested by logistic regression analysis. The diagnostic performance of the ACR/EULAR RA classification criteria corrected by US and MRI joint and tendon counts was evaluated using ROC analysis. Results. Thirty patients fulfilled the ACR/EULAR criteria [early RA (ERA) patients] and the remaining 15 failed to meet these criteria (non-RA). Carpal joint synovitis and tenosynovitis of the flexor tendons was found in 86.7% and 86.7% of patients with ERA on MRI compared with 63.3% and 50% on US, respectively (p < 0.05). The global MRI and US counts revealed a good diagnostic performance for RA diagnosis of both techniques, although MRI was statistically significantly better [area under the curve (AUC) = 0.959 and AUC = 0.853, respectively; z statistic = 2.210, p < 0.05]. MRI identification of carpal joint synovitis (OR 3.64, 95% CI 1.119–11.841), tenosynovitis of the flexor tendons (OR 5.09, 95% CI 1.620–16.051), and global joint and tendon count (OR 2.77, 95% CI 1.249–6.139) were in the multivariate logistic regression model the most powerful predictors of progression toward RA. In the group of ERA patients with US joint and tendon counts ≤ 10, a statistically significant difference was found between the diagnostic performance for RA of the ACR/EULAR criteria as previously described and the diagnostic performance of the MRI-corrected ACR/EULAR criteria (AUC = 0.898 and AUC = 0.986, respectively; z statistic = 2.181, p < 0.05). Conclusion. 3.0-T MRI identified a higher prevalence of synovitis in comparison to US in an early polyarthritis cohort. Both techniques have good diagnostic performance for RA although MRI reveals a significantly higher diagnostic capability. Synovitis of carpal joints and of flexor tendons as identified by MRI were the most powerful predictors of progression toward RA. In patients with US joint and tendon counts ≤ 10, MRI can significantly improve the diagnostic performance of the 2010 ACR/EULAR classification criteria.

A1.1 Obesity is a risk factor for worse treatment response in rheumatoid arthritis patients- results from reuma.pt

Objective Obesity is a traditional cardiovascular risk factor that affects one third of rheumatoid arthritis (RA) patients. Presently, the importance of obesity in RA activity remains unclear. This study aims to determine the influence of obesity on treatment response to biologic therapy evaluated by DAS28 at six months, in patients with RA, regardless of the targeted cytokine or cell, by analyzing a cohort of patients treated with anti-IL-6, TNFinhibitors (TNFi) or anti-CD20 therapies. Methods We conducted a retrospective longitudinal cohort study using the Rheumatic Diseases Portuguese Register (Reuma.pt). RA patients refractory to DMARD therapy, with at least 6 months of follow up after starting their first biologic therapy, with available data on weight and height at baseline were included. A DMARD naïve patients group was used as control Information was obtained on patient demographics, education, body mass index (BMI), present smoking status, disease duration, therapy, baseline disease activity score in 28 joints (DAS28), erosive disease, rheumatoid factor and anti-citrullinated protein antibodies, health assessment questionnaire (HAQ), type of biologic therapy (TNFi vs non-TNFi). BMI was categorised in two classes: non-obese (BMI <30) and obese (BMI > = 30 Kg/m2). Multivariate analysis was performed in order to evaluate the association between obesity and DAS 28 at 6 month and remission state (DAS28 <2.6). Results 317 patients treated for the first time with a biologic agent were included in this study. 23% were obese. We found a significant association between obesity and DAS28 at 6 months (β = 0.412 (0.045–0.779); p = 0.028). Other factors also showed a significant association namely baseline DAS28 (β = 0.514 (0.393–0.636); p < 0.001) and the use of a TNFi (β = 1.22 (0.787–1.653; p < 0.001). Considering disease remission the analysis did not show a significant association between obesity and DAS28 remission at 6 months for all biologic agents as a group (OR = 0.391 (0.132–1.161; p = 0.091). Baseline DAS28 (OR = 0.384 (0.264–0.597); p < 0.001) and the use of TNFi as a biologic therapy did show a significant association with achieving remission in these patients (OR = 0.037 (0.012–0.111); p < 0.001). In the 35 DMARD naïve patients evaluated we also found a significantly association of obesity and DAS28 at 6 months (β = 1.048 (0.227–1.829); p-value = 0.009) but not with remission (OR = 0.24 (0.006–1.938); p = 0.24). Conclusion Obesity predicts worse treatment response in rheumatoid arthritis. These results suggest that obese RA patients should be encouraged to reduce weight in order to improve disease control.

Years of Working Life Lost Caused By Osteoarthritis In Portugal.

§ The estimated prevalence of OA in the Portuguese population (50-64 yo) is 29.7% (knee:18.6%; hand:12.6%; hip:3.6%). § Among these, 61.8% were out of work versus 47.6% for those without OA (p=0.004). § OA is associated with early exit from work (unadjusted OR: 1.78; CI:1.19-2.65; p=0.005. Adjusted OR: 1.83; CI: 1.12-2.96; p=0.015), but not with official early retirement (OR: 1.18; CI:0.78-1.79; p=0.437). § Early exit from work potentially led to 162,735 YWLL (95 per 1000 inhabitants). § Early retirement contributed the most for these YWLL (58%; 94,432 YWLL), followed by unemployment (35%; 57,209 YWLL) and disability pensions (7%; 11,094 YWLL). § Women accounted for 80% of these YWLL (153 per 1000 female inhabitants). § A total of 161,621 PYWLL were estimated if early retirement is considered and 369,839 PYWLL for all forms of exit from work.

AB1155 Self-Reported Rheumatic Diseases and Early Retirement in Portugal – Results from the Portuguese Epidemiology Study on Rheumatic Diseases (Epireumapt)

Background Chronic diseases and in particular rheumatic diseases (RD) may lead to early retirement, generating substantial costs to society. Objectives We aim to examine the association between self-reported RD and early retirement by using large real-world observational data. Methods EpiReumaPt was a national, cross-sectional, population-based study conducted from September 2011 to December 2013. 10,661 inhabitants were randomly surveyed in order to capture and characterize all cases of RD within a representative sample of the Portuguese population, which were stratified by administrative territorial units (NUTSII). In this analysis we used all participants aged between 50 and 65 years old, near the official retirement age (N=2,792; females: 1,727). The association of self-reported RD and early retirement was tested using individual level logistic regression. All estimates were computed as weighted proportions, in order to take into account the sampling. Results 29.9% of the Portuguese population with ages between 50 and 64 years old were officially retired. Among these, 43.2% were retired due to ill-health, which in turn about a third (30.4%) was specifically due to RD. Thus, 13.1% of all retirees self-reported RD as the main reason for early retirement. More than a third (34.2%; females: 46.3%) of all study population self-reported RD, being also more likely to self-report other main chronic disease (OR: 3.4; CI: 2.53-4.65; p<0.001). 35.2% of RD respondents were retired versus 27.2% of those non-RD (p=0.025). Prevalence of self-reported RD seems to be associated with early retirement (unadjusted OR: 1.45; CI: 1.05-2.01; p=0.025). Some other characteristics are also associated with early retirement, in particular older age, male gender and presence of other chronic diseases. RD association tends to be independently associated with early retirement (adjusted OR: 1.41; CI: 1.03-1.95; p=0.031). Conclusions These results are in line with previous data from the National Health Survey conducted in Portugal nearly a decade ago and confirms the impact that self-reported RD still have on early retirement. Nevertheless, further analysis should be done in order to analyze clinically confirmed RD and to address the different RD and its relationship with early retirement. Disclosure of Interest None declared

BioRePortAP, an electronic clinical record coupled with a database: an example of its use in a single centre

AIMS To evaluate the efficacy and safety of the treatment of psoriatic arthritis (PsA) patients with tumor necrosis factor (TNF) antagonists in the Rheumatology Department of Hospital de Santa Maria using the BioRePortAP. METHODS The Portuguese Society of Rheumatology (SPR) developed an electronic medical chart coupled with a database for the follow up of PsA patients, the BioRePortAP, which was launched in May 2009. This evaluation was based on all the PsA patients that were on active treatment with TNF antagonists in September 2009 and were registered in the BioRePortAP. All the previous data on these patients were introduced in BioRePortAP using the prospective paper based follow up protocol that this Department was using since 1999. Only patients with more than 9 months of treatment were analyzed. RESULTS Forty-two patients with PsA, actively treated with anti-TNF agents in September 2009, for at least 9 months, were analyzed in BioRePortAP. Twenty-three patients were male (55%) and nineteen were female (45%). The average age of these patients was 49.8+/-10.9 years old, the average disease duration was of 10.7+/-5.6 years and the mean duration of biological therapy was of 37.8+/-27.8 months. For the 81% of patients with peripheral joint disease there was a mean reduction of more than 80% in the swollen and tender joint counts, and almost 50% in the health assessment questionnaire (HAQ) value. In the 19% of the patients with axial involvement the reduction of BASDAI and BASFI was not statistically significative. On top of that, PASI score suffered a reduction of 64%. Fourteen patients (33.3%) had to switch their TNF antagonist treatment. 58.8% of the switches were due to adverse effects and 41.2% due to therapy failure. Regarding the 56 adverse reactions registered, only one was a severe reaction. The remaining adverse reactions were not severe and 67% of them were due to infections. DISCUSSION The results of this first report of the use of the BioRePortAP in clinical practice confirm the efficacy and safety of TNF antagonist treatment in PsA. The results shown here elucidate the potential applications of BioRePortAP as a tool for efficacy and safety assessment of PsA patients treated with biotechnological drugs.

AB0835 Association Between Sociodemographic and Clinical Features with Radiographic Severity in Knee Osteoarthritis – Results from Epireumapt

Objectives To assess patient characteristics associated with radiographic severity in knee osteoarthritis (KOA) in a population-based study. Methods EpiReumaPt is a national epidemiologic, cross-sectional study of rheumatic diseases (RD) in the Portuguese population conducted from September 2011 to December 2013. From the 3877 patients assessed by a rheumatologist on the second phase of the study, we included all cases of KOA defined according to the American College of Rheumatology clinical and/or radiographic classification criteria. Knee x-rays were acquired using a standardized protocol and centrally scored according to the Kellgren-Lawrence (KL) scale. The knee osteoarthritis outcome score (KOOS) was used to assess KOA clinical features. Weighted stepwise multivariate logistic regression was used to assess which features associated with radiographic severity, after stratifying the disease in mild (grade 0 to 2) and severe (grade 3 and 4) KOA according to the KL scale. Results A total of 981 (weighted prevalence: 12.4%) patients were classified as KOA patients. Knee radiographs were available for 553 patients. From those, 318 (63.7%) had mild disease and 235 (36.3%) had severe disease. On the multivariate analysis, several patients features were significantly and independently associated to radiographic severity: age (OR: 1.08; p<0.001), obesity (OR: 2.7; p=0.014); dyslipidemia (OR: 2.73; p=0.002), the total number of non-rheumatic comorbidities (OR: 0.63; p<0.001); Country region (OR: 0.61; p<0.001); orthopedic intervention of the knee (OR: 4.71; p=0.004); KOOS symptoms subscale (OR: 0.96; p=0.001; higher KOOS, less symptoms). Alentejo region had the higher proportion of severe disease [56.0% (36.2-75.7)], whereas Lisbon area had the lowest [36.4% (26.9-45.8)]. Conclusions We found several clinical and sociodemographic features associated with radiographic severity in KOA patients. Our findings contribute to the understanding of disease progression mediators. A longitudinal evaluation is needed to validate these results. Disclosure of Interest None declared

A4.3 Differences of bone WNT regulators expression between fragility fractures and osteoarthritis patients

Introduction The importance of Wnt signalling, a crucial pathway for osteoblast differentiation and a master bone mass regulator as been recently highlighted. With this study, we aim to compare bone expression of Wnt regulators between fragility fracture and osteoarthritis patients. Methods Patients submitted to total hip replacement surgery either due to a fragility fracture or to osteoarthritis, at the Orthopedics department of Hospital de Santa Maria, were recruited. Clinical risk factors (CRFS) for osteoporotic fractures were collected. RNA was extracted from a small trabecular bone sample and analysed by quantitative real-time protein chain reaction (RT-PCR). Immunohistochemistry analysis for DKK1 and SOST was also performed. Results 118 patients submitted to total hip replacement surgery, 55 due to fragility fracture, were evaluated. Fragility fracture patients were predominantly women (84% vs 49%, p<0.001), significantly older (80 ± 7 vs 68 ± 12, p < 0.001) and had significantly more previous fragility fractures than the osteoarthritis group (33% vs 5%, p < 0.001). Univariate analysis showed that RANKl/OPG ratio, a marker of osteoclastogenisis, was significantly higher in the fragility fracture group (p < 0.001). On the other hand osteocalcin expression, a marker of osteoblast maturation was significantly lower in fragility fracture group (p < 0.001). Regarding Wnt regulators, WNT 10b (β = -0,398, p < 0.001) and DKK1 (β = -0,387, p < 0.001) expression was significantly higher in osteoarthritis group even after adjusting for age and gender. In multivariate analysis SOST (β = 0.236, p = 0.0411) was significantly higher in the fragility fracture group. Semi-quantitative analysis of immunohistochemistry results for DKK1 revealed a significantly higher staining scores (p = 0.04) in the osteoarthritis group. Conclusion In fragility fracture patients, bone SOST expression is upregulated. In osteoarthritis patients, DKK1 gene expression and protein staining is significantly higher than in fragility fractures. These results improve the knowledge of WNT disturbances in these two diseases and can be of help to identify new treatment targets.

A4.5 Procollagen type 1 amino-terminal propeptide is negatively associated with bone stiffness in subpopulations of patients submitted to hip replacement surgery

Background and Objectives Osteoporosis (OP) is a frequent disorder of bone metabolism. In OP, cortical bone changes lead to bone loss and deterioration of the microarchitecture increasing risk of fragility fractures of the hip. Bone turnover markers (BTM) reflect bone remodelling. Their role in daily clinical practice is still undefined. In a recent epidemiologic study, a relation between P1NP and hip fractures was found, suggesting both low and high levels of P1NP confer increased risk of osteoporotic fractures. We aim to analyse the relation between BTM and biomechanical features of the bone, in patients with stabilised osteoporosis and in patient with severe osteoarthritis. Materials and Methods We analysed patients submitted to hip replacement surgery in the context of severe OA or hip fragility fracture. The patients were asked for clinical data, blood samples and to perform dual x-ray absorptiometry. Blood biomechanical studies were performed and a bone cylinder was drilled from their femoral epiphyses. Stiffness, strength and toughness were assessed by young’s modulus, yield stress and energy until yield point, respectively. Results We analysed 299 patients, 163 patients with OP and 136 with severe OA. OA patients were more frequently men (67%, p < 0.001), significantly younger (67.5 ± 11.1y vs 78.9 ± 9.0y, p < 0.001) and fatter (body mass index (Kg/m2) 28.1 ± 4.7 vs 23.92 ± 4.1, p < 0.001). OA patients fell less (number of falls in the last year 0.44 ± 0.49 vs 0.12 ± 0.32, p < 0.001). Only 15% of OP patients were being treated. Stiffness, strength and toughness were significantly increased in OA group (p = 0.005, 0.02 and 0.004, respectively), with adjustment to age and sex. Alkaline phosphatase was higher in OP patients (p = 0.05, with adjustment to age, sex and BMI), the other parameters didn’t reach statistical difference. In OP patients, P1NP (coef = -1.42, p = 0.045) was associated with lower stiffness. In OA patients, P1NP (coef = -3.82, p = 0.006) and B-CTX (coef = -4.61, p = 0.035) were also associated with bone stiffness. P1NP was also associated with lower strength (coef = -0.058, p = 0.013). All analyses were adjusted to age, sex and BMI. Conclusions In both OA and OP patients, P1NP was associated with lower stiffness. This tendency was also found with strength in OA patients. This may reflect that extreme values P1NP associate with bone fragility. This study was performed on a post-surgery context and further studies in other populations should be done.

AB0881 Biologic Disease Modifying Anti-Rheumatic Drug Use in the Treatment of Juvenile Idiopathic Arthritis: Data from the Rheumatic Diseases Portuguese Register, Reuma.Pt

Background The Portuguese Society of Rheumatology developed the Rheumatic Diseases Portuguese Register (Reuma.pt) encompassing also Juvenile Idiopathic Arthritis patients followed by rheumatologists and pediatricians. Objectives 1. To obtain an overview of biological agents use in Portuguese children with JIA. 2. To assess the effectiveness and safety of biological therapy at 6 months and 1 year of treatment. Methods We retrieved data from Reuma.pt, until December 2013. We collected baseline patient and disease characteristics of patients with JIA who started treatment with biological agents. Follow-up data were analyzed and are presented at 6 months and 1 year. Disease activity was assessed using the number of active joints, ESR and CHAQ. Results 812 patients with JIA,227 received biological therapy.The mean age at disease onset of patients treated with biologic DMARDs was 6.9±4.7years and the mean age for starting biological therapy was 16.1±9.4years. The most common JIA categories were polyarticular RF negative (23.3%), polyarticular RF+(17.5%) and extended oligoarticular (16.0%).The median duration of the first biological agent was 5.76years. Most patients were treated with antiTNF as first line (90.3%):etanercept 69.2%,adalimumab 12.8%,infliximab 8.4%. Mean baseline active joint count was 5.1±5.8, decreasing to 1.2±2.4 and 1.0±3.1 after 6 months and 1 year of therapy. Mean ESR was 33.9±25.3 mm/1sth and 26.9±23.9 and 19.1±180 after 6 months and 1 year. CHAQ decreased from 0.8±0.7 to 0.4±0.5 and 0.4±0.5 at 6 months and 1 year. 14.1% switched once to other biological therapy (3.08% in the first 6 months,4.4% in the first year), 5.73% switched twice (0.88% in the first 6 months,1.76% in the first year) and 2 patients (0.88%) switched 3 times after the first year of treatment. 14 serious adverse events were reported leading to discontinuation of the treatment, 6 in the first 6 months and 8 in the first year of treatment. There were no reported deaths. The one-year treatment retention with biological agents was 91%. Conclusions JIA patients treated with biologics and registered in Reuma.pt showed a good profile of effectiveness and safety at 1 year. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3142