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Background:Hepatitis B virus (HBV) vaccination is recommended for rheumatic patients starting biologic therapy. There is some evidence that HBV vaccination is effective in patients under conventional disease modifying anti-rheumatic drugs (DMARDs), but it is currently unclear whether this also applies to biologics.Objectives:To assess the efficacy and safety of HBV vaccination in patients with rheumatic diseases treated with biologics.Methods:We included patients with any inflammatory rheumatic diseases treated with any biologic, who were negative for anti-HBs and anti-HBc and had never been vaccinated for HBV. Engerix B® was administered at 0, 1 and 6 months and anti-HBs was re-assessed ≥1 month after last dose. Response was defined as anti-HBs>10IU/L and compared against healthy controls (HC) undergoing Occupational Health immunization. Disease flare was evaluated before and until at least 1 month post-vaccination. We recorded serious adverse events (SAE) and immune-related disorders not previously present.Results:We included 67 patients, most treated with TNF inhibitors (TNFi), and 70 HC (Table 1). Most patients were taking concomitant DMARDs (69%) and were in remission/low disease activity (59%). Only 20 patients (30%) had a positive response to vaccination, in comparison to 68 HC (97%, pst/2nddose, deemed not to be related to vaccination. One RA patient on infliximab had bilateral uveitis 2 months after the 1stvaccine dose, which resolved with topical therapy.Table 1.Baseline characteristics of study participants.Patients (n=67)Controls (n=70)pAge (years)56 ± 946 ± 9Female (%)40 (60)62 (89)Diagnosis (%)RA32 (48)PsA / AS18 (27) / 13 (19)Other4 (6)Disease duration (years)17 ± 10Biologic (%)TNF-inhibitor53 (79)Tocilizumab / Abatacept6 (9) / 1 (1)Rituximab / Belimumab2 (3) / 4 (6)Anakinra1 (1)Conventional DMARDs (%)MTX / LEF39 (58) / 1 (1)SSZ / Other6 (9) / 3 (4)None21 (31)Prednisolone (%) / Dose (mg)29 (43) / 5.6 ± 2.1DAS283.1 ± 1.4ASDAS2.2 ± 1.4Conclusion:In this study, HBV vaccination response was poor and lower in rheumatic patients treated with biologic therapy than in healthy adults. Vaccination was overall safe but there were 4 severe flares and 3 SAE that lead to treatment switch/interruption, although causal association is difficult to establish. Our data reinforce the recommendation for HBV vaccination prior to starting biologic therapy, possibly even as soon as the diagnosis is established. Alternative HBV vaccination strategies should be investigated in patients already treated with biologics.Disclosure of Interests:Vasco C Romão: None declared, Pedro Ávila-Ribeiro Grant/research support from: Novartis, Maria João Gonçalves: None declared, Ana Rita Cruz-Machado: None declared, André Guerreiro: None declared, Vítor Teixeira: None declared, Ana Valido: None declared, Joana Silva-Dinis: None declared, Elsa Vieira-Sousa: None declared, Maria João Saavedra: None declared, Ema Leite: None declared, Rui Tato Marinho: None declared, Joao Eurico Fonseca: None declared

Introduction Topical application of tranexamic acid to the knee joint before closure in total knee arthroplasty reduces postoperative bleeding without increase in complication. However, it is unknown the effectiveness of topic TXA performed with other topical medications, like povidone-iodine solution. Materials and methods One hundred and twenty-five patients were randomized to receive 100 mL of povidone-iodine solution (control: group A) or 1.5 (group B) and 3.0 g (group C) of topical TXA in povidone-iodine solution applied into the knee before closure in total knee arthroplasty. Results The patients in the TXA groups had higher mean postoperative hemoglobin levels ( P = 0.01 and P = 0.03 in groups B and C, respectively) and a reduced postoperative blood loss in the TXA groups ( P = 0.07 and P = 0.09 in groups B and C, respectively). No significant complications were observed. Discussion In this study, topical application of tranexamic acid after total knee arthroplasty together with povidone-iodine solution results in higher postoperative hemoglobin levels and lower blood loss compared with those in the control group without other complications. Level of evidence I – I: high-powered prospective randomized trial.

Resumo: Os sarcomas primários do pulmão são neoplasias raras e potencialmente agressivas, que devem ser distinguidos de outros tumores pulmonares malignos e cujo comportamento biológico não está completamente esclarecido.Os autores apresentam um caso clínico de sarcoma pleomórfico indiferenciado do pulmão, que foi diagnosticado a um homem de 66 anos. Na altura do diagnóstico foi realizada desobstrução brônquica por laser e radioterapia, tendo sido posteriormente observada uma sobrevivência superior a 11 anos. Abstract: Primary sarcomas of the lung are uncommon, potentially aggressive neoplasms that need to be distinguished from other malignant pulmonary tumors and whose biological behavior is as yet not fully understood.Primary undifferentiated pleomorphic sarcoma was diagnosed in the right lung of a 66 year-old man, who has survived over 11 years after treatment with endobronchial tumor debulking by laser therapy and radiotherapy. Palavras-chave: Neoplasias pulmonares, Sarcoma pulmonar, Sarcoma pleomórfico indiferenciado pulmonar, Sobrevivência prolongada, Keywords: Lung neoplasm, Pulmonary sarcoma, Undifferentiated pleomorphic pulmonary sarcoma, Long survivors

Primary sarcomas of the lung are uncommon, potentially aggressive neoplasms that need to be distinguished from other malignant pulmonary tumors and whose biological behavior is as yet not fully understood.Primary undifferentiated pleomorphic sarcoma was diagnosed in the right lung of a 66 year-old man, who has survived over 11 years after treatment with endobronchial tumor debulking by laser therapy and radiotherapy. Resumo: Os sarcomas primários do pulmão são neoplasias raras e potencialmente agressivas, que devem ser distinguidos de outros tumores pulmonares malignos e cujo comportamento biológico não está completamente esclarecido.Os autores apresentam um caso clínico de sarcoma pleomórfico indiferenciado do pulmão, que foi diagnosticado a um homem de 66 anos. Na altura do diagnóstico foi realizada desobstrução brônquica por laser e radioterapia, posteriormente foi observada uma sobrevivência superior a 11 anos. Keywords: Lung neoplasm, Pulmonary sarcoma, Undifferentiated pleomorphic pulmonary sarcoma, Long survivors, Palavras-chave: Neoplasias pulmonares, Sarcoma pulmonar, Sarcoma pleomórfico indiferenciado pulmonar, Sobrevivência prolongada

Background Registries are becoming an increasingly important source of data, providing additional information on the use of biologics in clinical practice. The real-world clinical data currently available regarding the use of SC anti-TNFs is still limited. Therefore, it is of utmost importance to increase the knowledge of Golimumab (GLM) effectiveness in the clinical practice. Objectives This study was designed to access the effectiveness of SC GLM 50 mg/monthly + MTX through 52 weeks of treatment in biologic-naive RA patients. The primary objective was to investigate the proportion of patients achieving clinical remission (DAS28ESR 0.22); and the effect of treatment on DAS28 individual components. Methods This was a retrospective non-interventional study based on the Rheumatic Diseases Portuguese Register (Reuma.pt). It was conducted in a cohort of patients aged >18 years with active RA despite previous treatment with conventional DMARDs, biologic-naive, who started SC GLM+MTX, from March 2011 to August 2015. The cumulative incidence of achieving clinical remission, treatment persistence and functional response/remission were estimated using survival analysis. Cox regression was used to calculate the hazard ratios. Results A total of 109 patients (86.3% female, mean age 55.5±13.2 years; mean age of diagnosis 45.5±13.5 years, rheumatoid factor 78% positive) met the study criteria. Ninety-three had a follow up of at least 52 weeks (i.e. all patients who started treatment before August 2014). At week 52, 38.3% of patients were on clinical remission, 91.9% achieved functional response and 35.2% were on functional remission (HAQ Conclusions This is the first Golimumab data analysis generated from the Portuguese registry Reuma.pt. Our results are in agreement with data from other national registries and demonstrate the long-term effectiveness and the high treatment persistence rates of GLM through 52 weeks. Disclosure of Interest A. F. Mourao Consultant for: Merck Sharp & Dohme, C. Ribeiro: None declared, J. Borges: None declared, M. J. Goncalves: None declared, M. Bernardes: None declared, S. Fernandes: None declared, R. Dezerto Employee of: Merck Sharp & Dohme, P. A. Laires Employee of: Merck Sharp & Dohme, P. Machado Employee of: Merck Sharp & Dohme, M. Eusebio: None declared, M. J. Santos: None declared, H. Canhao: None declared

Background and objectives B-cells play several important roles in rheumatoid arthritis (RA) pathogenesis, namely through autoantibody production, antigen presentation and T cell activation, but few studies have been performed in untreated early RA patients. Therefore, the main goal of this study was to characterise B-cell phenotype and B-cell gene expression levels since early RA onset in comparison with the chronic phase of the disease. Materials and methods Blood samples were collected from untreated early RA (ERA) patients ( Results The frequency of total CD19 + B-cells in circulation was similar between controls and patients’ groups, but established RA had significantly increased frequencies of double negative (IgD-CD27-) B-cells in comparison with controls. CXCR5 B-cell expression was significantly increased in both ERA and established RA in comparison with controls, but no significant differences were observed in BAFF-R, TACI, BCMA, CD69, CD86, HLA-DR, TLR9, CD95, IgM and CD5 B-cell expression between all groups analysed. Furthermore, alterations in B-cell gene expression levels were found in BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M in ERA and established RA patients when compared to controls, but no significant differences were detected in AID, BCMA, CXCR5, TLR7 and TLR10 B-cell gene expression between all groups. In addition, CXCL13 and sCD23, but not BAFF serum levels, were significantly increased since early RA. Conclusions CXCR5 B-cell expression and CXCL13 serum levels are significantly increased in untreated early RA (

Background Biologic therapy for rheumatic diseases (RD) and inflammatory bowel disease (IBD) has been associated with increased risk of reactivation of latent infections such as hepatitis B (HB). However, the actual risk of HB reactivation is still unclear, especially in low-endemic countries such as Portugal. Objectives To evaluate the serologic HB profile of rheumatic and IBD patients exposed to biologics in two centres. To characterize and assess the incidence of HB reactivation in patients with evidence of past HB infection. Methods We collected available HB serology of rheumatic patients that ever started biological therapy at our departments. We reviewed the clinical course to identify reactivation cases, defined as raising transaminases, de novo detection of AgHBs and/or positive viral load. Anti-HBc positive patients were studied as to clinical and treatment characteristics. Results We identified 934 patients with available data on HB serologies (710 RD, 224 IBD) that corresponded to a cumulative biologics exposure of 3904.4 patient-years. All of the patients were AgHBs negative, 72 (8.5%) were anti-HBc positive and viral load was undetectable in every case (Figure 1). In the anti-HBc positive subpopulation, two thirds were females, median age at biologic start was 54.1 years (interquartile range [IQR] 41.3-60.6) and median disease duration was 6.6 years (IQR 3.3-11.1). Sixty-one had a RD diagnosis (9.8% of total; 31 rheumatoid arthritis [10.9%], 12 ankylosing spondylitis [6.9%], 10 psoriatic arthritis [11.2]) and 11 had IBD (5.0% of total; 10 Crohn9s disease [5.7%], 1 ulcerative colitis [2.5]). Amongst anti-HBc positive patients, the most frequent initial biologic was infliximab (38.9%), followed by etanercept (31.9%), adalimumab (12.5%), golimumab (5.6%), tocilizumab (5.6%) and rituximab (5.6%). Only 5.6% eventually stopped biologic treatment during follow-up. Forty-four patients (61%) were concomitantly treated with methotrexate (69% of RD and 18% of IBD patients), 43 (60%) with other DMARDs (56% of RD and 82% of IBD patients) and 51 (71%) were on corticosteroids (71% of RD, 73% of IBD patients). No patient received prophylactic antiviral therapy and there was only one case of HB reactivation, a Crohn9s disease patient with prior history of acute HB, anti-HBc/anti-HBs positive and initially treated with adalimumab plus azathioprine. She was switched to infliximab because of poor response and at the time she had lost anti-HBs positivity while maintaining anti-HBc. Severe HB reactivation ensued after 13 months of treatment, infliximab was stopped and anti-viral therapy started with a favorable outcome. Conclusions In our cohort of 934 rheumatic and IBD patients, anti-HBc positivity was infrequent, viral load undetectable and there were no chronic HB cases. There was one case of HB reactivation in a anti-HBc+/anti-HBs- patient treated with infliximab. In a low incidence setting, HB reactivation following biologic therapy is likely to be a much rarer event than what has been previously reported. Disclosure of Interest None declared

Background Fabry9s disease (FD) is a lysosomal storage disorder initiated by sphingolipid accumulation owing to a deficiency of the enzyme a-galactosidase A (a-Gal A). Classically affected males present with pain (more frequently, acroparestesias in the extremities, but also episodes of joint pain associated with fever and high erythrocyte sedimentation rate), cutaneous lesions and gastrointestinal symptoms. During the course of the disease, renal, cardiac and cerebrovascular complications often develop, causing high morbidity and premature death. Clinical picture in females is more heterogeneous, with some patients having a milder phenotype. The prevalence of FD among patients diagnosed as juvenile idiopathic arthritis (JIA) is unknown, but as musculoskeletal pain may be a chief complaint at presentation, the presence of misdiagnosed cases is probable. Biochemical analysis (such as measurement of α-Gal enzyme activity in plasma) is frequently used for diagnosis purposes. However, molecular analysis is a more sensitive method, allowing the diagnosis in the subset of patients who have normal enzymatic levels. The correct diagnosis can prevent the progression of FD and avoid the exposure to immunosuppressant treatments used in JIA children that are useless for this condition. Objectives With this study, we aim to calculate the frequency of FD in a population of JIA patients. Methods Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded at regular time points, according to clinical practice in the Portuguese nationwide register Reuma.pt. Molecular genetic testing to detect GLA mutations was performed. After the multiplex PCR technique for amplification of DNA fragments to optimize reactions, direct sequencing of the complete sequence of GLA gene (7 exons) was performed to identify mutations. Results From a cohort of 292 patients with JIA (188 female, 104 male), mutations were identified in 5 patients (all female). 4 patients had the alpha-Gal A gene mutation D313Y, a rare variant, that is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This patient is a girl that presented with a persistent oligoarticular form of JIA at the age of 3 years old, now being treated with steroid intra-articular injections and conventional DMARDs. Conclusions Excluding the D313Y alteration, which is thought not to be clinically relevant, FD mutation (R118C) presented in a frequency of 1 in 292 individuals within this nationwide JIA cohort. As our patient is a heterozygotic female, we cannot ascertain a final diagnosis of FD. The patient and her family are under further clinical investigation. A low threshold for FD screening in JIA patients should be warranted. An early diagnosis of FD in those patients can lead to implementation of a specific therapy and allow the study of their families. References Niemann M, et al. Lyso-Gb3 Indicates that the Alpha-Galactosidase A Mutation D313Y is not Clinically Relevant for Fabry Disease, JIMD Rep. 2013;7:99-102 Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is a multi-organ immune-mediated disease that affects predominantly women at reproductive age but may present itself at any age. Age at disease onset has a strong modulating effect on clinical presentation and course of disease. Although young patients may have a more aggressive disease, controversies persist regarding the impact of age at disease onset on SLE outcome. Objectives Characterize childhood-onset, adult-onset and late-onset SLE and assess whether disease outcome differs in these three patient groups. Methods Patients with childhood-onset (diagnosis ≤18 years) SLE fulfilling ACR 1997 criteria were identified in the Portuguese registry Reuma.pt/SLE and compared with adult-onset (≥19y and ≤49 years) and late-onset (≥50 years) SLE patients paired for disease duration. Results Two hundred and sixty seven SLE patients with mean disease duration of 11.9±9.3 years were analyzed (Table 1). The number of fulfilled ACR criteria was significantly higher in childhood-onset SLE. A greater proportion of women, higher prevalence of arthritis and anti-SSA antibodies were noted in the adult-onset group. Hypertension, diabetes and thyroid disease were significantly more prevalent in late-onset SLE. Disease activity at last visit evaluated using the SLEDAI-2K was significantly higher in childhood-onset group than in the late-onset counterparts. SLICC/ACR damage index was numerically higher in late-onset SLE and significantly more patients in this group had irreversible damage. Cyclophosphamide and mycophenolate mophetil were used more frequently in childhood-onset SLE patients. Conclusions The skin, kidney and neurological involvement are most common in childhood-onset, as well as the use of immunosuppressants, supporting the concept of a more severe disease. In contrast, patients with late-onset SLE have more comorbidities and irreversible damage. The age of SLE onset has a significant impact not only on the clinical characteristics and disease activity, but is also important for disease outcome. Disclosure of Interest None declared

Background and objectives B cells play several important roles in rheumatoid arthritis (RA) pathogenesis, namely through autoantibody production, antigen presentation and T cell activation. The use of immunosuppressive drugs such as TNF-inhibitors and/or Il-6 receptor antagonist, tocilizumab, in RA might affect the circulating numbers of B cells and their activation state. The main goal of this work was to study the effect of TNF-inhibitors and tocilizumab on B cell phenotype and gene expression before and after treatment. Materials and methods Blood samples were collected from established RA patients treated with TNF-inhibitors (n = 10) and tocilizumab (n = 9) before and after treatment, and from healthy donors (n = 15). B-cell subpopulations were characterised by flow cytometry and B-cell gene expression was analysed by real-time PCR on isolated B-cells. Results The frequency of circulating B cell subpopulations was similar between controls and established RA patients irrespective of treatment. The mean fluorescence intensity (MFI) of TACI, CXCR5 and HLA-DR expressed on CD19 + B-cells was significantly increased in TNF-treated patients when compared to controls. A significant decrease of CD86 and increase of CD95 MFI was observed in CD19 + B-cells after TNF treatment. In tocilizumab-treated patients, HLA-DR and TLR9 MFI were significantly increased in CD19 + B-cells when compared to controls. No significant differences were observed in BAFF-R, BCMA, IgM and CD69 MFI in both groups of patients compared to controls. BAFF-R, Bcl-2, β2-microglobulin, FcgR2A, TLR7 and TLR10 gene expression were significantly increased after treatment with TNF and/or tocilizumab in comparison with controls, but no significant differences were observed when comparing baseline and follow-ups. Conclusions In RA, the use of TNF-inhibitors and/or tocilizumab treatment affects B-cell phenotype in circulation, but the effect of these drugs on B-cell gene expression is less evident. The decreased levels of CD86 expression and increased CD95 MFI on B-cells after TNF treatment support an inhibition of B-cell activation. Our results suggest that TNF-inhibitors and tocilizumab help to reduce B-cell infiltration in the joints and these activated B-cells express higher HLA-DR and CXCR5 levels in circulation.

Introduction Topical application of Tranexamic acid to the knee joint before closure in total knee arthroplasty reduces postoperative bleeding without increase in complication. However, it is unknown the effectiveness of topic TXA performed with other topical medications, like povidone-iodine solution. Materials and methods One hundred and twenty-five patients were randomized to receive 100 mL povidone-iodine solution (control: gr. A) or 1.5 (gr. B) and 3.0 g (gr. C) of topical TXA in 100 mL of povidone-iodine applied into the knee before closure in total knee arthroplasty. Results The patients in the TXA groups had higher mean postoperative hemoglobin levels (P = 0.01 and P = 0.03 in groups B and C, respectively) and a reduced postoperative blood loss in the TXA groups (P = 0.07 and P = 0.09 in groups B and C, respectively). No significant complications were observed. Discussion In this study, topical application of Tranexamic acid after total knee arthroplasty together with povidone-iodine solution results in higher postoperative hemoglobin levels and lower blood loss compared with those in the control group without other complications. Level of evidence I – I: High-powered prospective randomized trial.

This paper reports on the comparison of three modeling approaches that were applied to a fed batch evaporative sugar crystallization process. They are termed white box, black box, and grey box modeling strategies, which reflects the level of physical transparency and understanding of the model. White box models represent the traditional modeling approach, based on modeling by first principles. Black box models rely on recorded process data and knowledge collected during the normal process operation. Among various tools in this group an artificial neural networks (ANN) approach is adopted in this paper. The grey box model is obtained from a combination of first principles modeling, based on mass, energy and population balances, with an ANN to approximate three kinetic parameters -- crystal growth rate, nucleation rate and the agglomeration kernel. The results have shown that the hybrid modeling approach outperformed the other aforementioned modeling strategies.

Background Biologic therapy for rheumatic diseases has been associated with increased risk of latent infections reactivation such as tuberculosis or hepatitis B (HB), due to severe immunosuppression. However, the actual risk of HB reactivation is still unclear regarding the several biologics available, especially in low-incidence countries such as Portugal. Objectives To evaluate the serologic HB profile of biologic-treated rheumatic patients in a single centre and assess the incidence of HB reactivation. Methods We retrospectively collected electronically available HB serology of rheumatic patients that ever started biological therapy at our department and we reviewed the clinical course to identify reactivation cases, defined as raising viral load and transaminases. Results We included 288 patients with available electronic data on HB serologies. Mean age was 43.9±15.7 years (3.1 to 82.3 years), disease duration was 10.9±9.5 years, 63.9% of patients were female and the most common rheumatic disease was rheumatoid arthritis (112, 38.9%), followed by ankylosing spondylitis (76, 26.4%) and psoriatic arthritis (54, 18.8%). As first biologic, 254 patients (88.2%) started anti-TNF agents, 14 (4.9%) rituximab, 11 (3.8%) tocilizumab and 9 patients (3.1%) another biologic. 30 patients (10.4%) eventually stopped biologic treatment. 185 patients (64.2%) were treated with concomitant methotrexate (mean dosage 15.7±5.4mg), 81 (28.1%) with other DMARDs and 169 (58.7%) were treated with corticosteroids (58.7%). All of the 288 patients were HBsAg negative and 23 were anti-HBc positive (9%). The 23 anti-HBc positive patients did not differ significantly from the overall population in terms of age, gender distribution, disease duration, follow-up time, biologic discontinuation or biologic started. No patient received prophylactic antiviral therapy and there were no cases of reactivation or isolated rise in viral load during a cumulative biologic exposure of 1005.6 patient-years (Fig. 1). Conclusions In our cohort, there were no cases of HB reactivation on the 288 patients treated with biologic therapy. Anti-HBc positivity was infrequent, viral load was undetectable in all cases and no chronic HB cases were detected. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4716

Background Systemic lupus erythematosus (SLE) is characterized by female predominance with male to female ratio around 1:10. Differences regarding clinical manifestations, disease activity, damage and mortality between men and women with SLE have been reported. Overall it is recognized that gender may affect SLE phenotype, but results concerning disease severity and prognosis are still a matter of debate. Objectives Characterization of Portuguese SLE male patients, focusing demographic, clinical, and laboratorial features. Methods All SLE patients from the Portuguese Lupus Register, Reuma.pt/LES were included. Demographic, clinical and therapeutic data were analyzed upon records from the last visit. Student t-tests, chi-square tests and Fisher9s exact tests were used to compare male and female patients. Analyses were further adjusted to age and disease duration. Results Of the 1510 SLE patients registered in Reuma.pt/LES, 122 (8%) are men. Male patients had later onset (39.4±20.6y vs 35.6±14.1y; p=0.005) and shorter disease duration (10.7±7.6y vs 14.1±9.0 y; p=0.0001). Mean current age, racial distribution and education level was similar in the two groups. Serositis, renal involvement and hemolytic anemia were more prevalent in men while, photosensitivity, alopecia, oral ulcers and arthritis were more commonly found in women (Table 1). Thyroid disease was more frequent in women (11.4 vs 2.3%). Cardiovascular risk factors had a similar distribution between these groups. Accumulated damage assessed by the SLICC damage index (SDI) and disease activity, assessed by SLEDAI-2K at last visit were similar in the two groups, with adjustment to age and disease duration. Antimalarial drugs and steroids were used more frequently in women. Conclusions Male patients with SLE are older at disease onset and present a distinct phenotype with less cutaneous, mucous membranes and articular manifestations. However, disease outcome evaluated by the SDI is comparable in men and women, which is in line with observations from other European cohorts. The acknowledgement of the effect of gender on disease manifestations may help physicians in the timely introduction of an appropriate care. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4615

Background Many patients with a clinical diagnosis of Systemic lupus erythematosus (SLE) do not fulfill the ACR 1997 classification criteria (ACR997). Consequently, patients included in SLE studies might not be representative of the real spectrum of the disease. The new SLICC 2012 classification criteria (SLICC912) were proposed to improve the sensitivity of SLE classification. However, these criteria require external validation. Objectives To compare the sensitivity for SLE diagnosis of the ACR997 and SLICC912 classification criteria sets in a real life, multicenter, international SLE population. Methods We included in this cross-sectional observational study all patients with a clinical diagnosis of SLE followed at the participating Rheumatology centers and registered in the Portuguese and Spanish national registries (Reuma.pt and RELESSER, respectively). For each patient, we evaluated the fulfillment of the ACR997 and SLICC912 criteria. The sensitivity for SLE diagnosis of each classification set was calculated. We compared the proportion of cases fulfilling ACR997 and SLICC912 using the McNemar9s test. To compare dichotomous variables in two independent populations, we applied a Chi-square or Fisher9s exact test, as appropriate. The statistical significance level was p Results We included 2055 SLE patients (female = 91.4%; Caucasian =93.5%; age at disease onset = 33.1±14.4; age at SLE diagnosis = 35.3±14.7; age at SLE criteria scoring = 47.4±14.6) from 17 centers. The sensitivity for SLE diagnosis was higher with the SLICC912 (93.1%) compared with the ACR997 (85.6%) (p The sensitivity for SLE diagnosis increased with longer disease duration, for both the ACR997 and SLICC912 (p 20 years of disease. Conclusions In real-life clinical setting, the SLICC912 classification criteria present a higher sensitivity for SLE compared to ACR997. The SLICC912 might allow a SLE classification earlier in the disease course. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2506

Background Systemic lupus erythematosus (SLE) affects predominantly women of reproductive age. However, in about 15% of patients SLE begins before the age of 18 years (early-onset) and in 10-20% of patients SLE is first diagnosed after the age of 50 years (late-onset). The age at disease onset significantly impacts on clinical presentation, disease course, response to treatment and prognosis. Objectives To compare demographic, clinical features and disease outcome between patients with early-onset and those with late-onset SLE and to determine whether patients9 age affects the time interval until diagnosis. Methods All SLE patients from the Portuguese registry Reuma.pt/LES with disease onset at age≤18 years-old or at age≥50 years-old were included. Patients9 data were cross-sectionally analyzed upon records from the last visit. The differences between groups with early and late onset were determined by Student t-tests, chi-square or Fisher9s exact tests. Results 313 SLE patients were included (157 early-onset; 156 late-onset). In the early-onset group, 88% were women, mean disease duration 16.8±10.5y and mean age of diagnosis 17±5.9y. Higher education level was noted in the younger group. 81.6% of patients with late-onset SLE were women, mean disease duration 9.37±5.2y and mean age of diagnosis 60.5±7.5y. Photosensitivity, arthritis and neurological disorder were statistically more prevalent in the late-onset group. Anti-Sm positivity was observed more frequently in early-onset SLE. Co-morbidities were also more common in this age group. Disease activity evaluated using the SLEDAI-2K was higher in the early-onset (3.0±3.3 vs 2.0±2.8; p=0.01) while accumulated damage was higher in the older age group (1.0±1.3 vs 0.69±1.4; p Conclusions Patients with late-onset SLE have more co-morbid conditions and greater accumulated damage despite shorter disease duration and lower disease activity. Age of onset has a significant impact not only on the clinical characteristics and disease outcome, but also on time until diagnosis. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5306

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 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.

Background Previous studies have shown that high Bone Mineral Density (BMD) in patients with advanced hip osteoarthritis was not a protective factor for bone fragility. Although measures of bone mineral content are strongly correlated with bone mechanical performance, they do not fully explain the response of bone to mechanical stresses. Bone abnormalities are found in patients with Chronic Kidney Disease (CKD). Evaluating the effect of CKD on bone mechanical properties in patients with hip OA may shed some light into the complex pathways of joint pathology in these patients. Objective To assess the association between CKD and trabecular bone mechanical properties in patients with hip osteoarthritis. Materials and Methods 37 Hip OA patients submitted to total hip replacement surgery were recruited. Clinical and demographical data were collected, a dual X-ray absorptiometry (DXA) was performed and fasting blood samples were collected at the time of surgery to assess creatinine and parathormone (PTH) serum levels. Previous creatinine levels were assessed to establish chronicity. Femoral epiphyses were collected and trabecular bone cylinders drilled in order to perform compression mechanical tests. Results Among the 37 hip OA patients 8 (21.6%) had CKD and 29 (78.4%) had normal renal function. There were no differences between groups regarding gender, age, body mass index and T-score (-1.5 vs -2.1, p = 0.305). However, there were more smokers among patients with CKD as compared to those with normal renal function (50% vs 10.3%, p = 0.027). As expected, patients with CKD had higher PTH levels as compared to those with normal renal function, however not reaching statistical significance (100.05 pgmL vs 37.41 pg/mL, p = 0.71). The association between trabecular bone mechanical properties with CKD tested by univariable analysis in hip OA patients revealed to be statistical significant only for stiffness (β = -187.19; p = 0.045). Multivariate regression analysis using forward selection demonstrated that in hip OA patients CKD was negatively associated with strength (β = -12.02; p = 0.038), stiffness (β = -471.77; p = 0.043) but not with toughness (β = -0.03; p = 0.192) adjusting for age, gender, BMI, smoking status, and T-score. The inclusion of PTH serum levels on each model renders the association between CKD and trabecular bone mechanical properties not statistical significant. Conclusions Our work suggest that, in patients with advanced hip OA, CKD is an independent risk factor for poor trabecular bone mechanical properties and that this effect is independent of bone mineralization status.

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 2 ) 28.1 ± 4.7 vs 23.92 ± 4.1, p 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.

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, in which severe organ damage can occur. B cells play an important role in SLE pathogenesis. Rituximab (RTX) has been used for SLE therapy, after failure of first-line immunosuppressive therapy. Evidence of efficacy is still short, and RTX use was based in observational studies and case reports. Recently, two randomized controlled trials of RTX failed to demonstrate efficacy in SLE. Objectives We aim to review the experience of our two hospitals with RTX therapy in SLE patients. Methods We considered all SLE patients registered in the Portuguese Register (Reumapt) from two centres in Lisbon (Hospital de Santa Maria and Hospital Garcia de Orta) and focused our study on the subgroup of patients with history of rituximab exposure. Results Our population of SLE patients is constituted by 305 patients (95,08% females), mean age 45.52±14.97. Mean age at diagnosis was 35.86±14.86 years old. Sixteen patients (5.91%) were treated with rituximab. In these patients, age at diagnosis was 34.6years-old, similar to other SLE patients. Organ involvement was characterized based on ACR criteria: cutaneous (50%), articular (77%), neurological (16.7%), renal (33%), serositis (33%). These patients had a significantly (p The mean age at the beginning of treatment was 41.87years, in average 7.86 years after the diagnosis. Clinical indications for Rituximab treatment were haematological involvement (9 patients, 50%), renal involvement (3 patients, 17%), polyarthritis (2 patients, 11%) and systemic disease activity (1 patient), that did not respond to first-line treatments. Until January 2013, the maximum duration of RTX treatment was 7.34 years (mean 2.56). Previous therapy included corticosteroids (100%), azathioprine (33%), mycophenolate mophetil (22%), cyclosporine (11%) and methotrexate (5.6%). Five of eight patients with thrombocytopenia had a sustained response to rituximab. One patient with haemolytic anemia also had a sustained response. In one patient with lupic nephritis class IV, the disease relapsed after 6 months The other two patients with nephritis (both class IV) had sustained response, which enabled to lower the dose of other immunosuppressive drugs. Three adverse effects were reported: one infectious complication (1 case of olecranian bursitis, with isolation of Staphylococcus aureus), hypersensivity reaction during the infusion and an episode of uveitis. Conclusions In our pratice, RTX has been used as second/third line treatment, after failure of other immunosupressive drugs, showing benefit in our patients. A distinctive immunological profile appears to exist in these patients who failed first line therapies. Low rate of adverse events was reported. References Joan T. Merrill et al, Efficacy and Safety of Rituximab in Moderately-to-Severely Active Systemic Lupus Erythematosus, Arthritis & Rheumatism, Vol. 62, No. 1, January 2010, pp 222–233 Disclosure of Interest None Declared

Background Reuma.pt, the Rheumatic Diseases Register from the Portuguese Society of Rheumatology has recently expanded its coverage to Systemic Lupus Erythematous (SLE) patients, the Reuma.pt/LES. Reuma.pt/LES is a web-based platform launched in September 2012 that simultaneously serves as a nationwide registry and as an electronic medical record. Its aim is to register all patients with SLE and follow them up in a standard manner in order to improve the monitoring and clinical care for patients with SLE while simultaneously increase the knowledge of this disease. Methods The authors present the structure and the functioning of this national project, giving as an example the subpopulation of patients with SLE from two centres in Lisbon (Hospital Santa Maria and Hospital Garcia de Orta) included in Reuma.pt/LES. Results 878 patients from all the country with the clinical diagnosis of SLE were registered in the database Reuma.pt/LES until January 2013. Recorded information includes demographics, work status, life-styles, ACR and SLICC 2012 classification criteria, thrombotic and obstetric manifestations, SLE disease activity at each visit, fatigue scale, health related quality of life measures (SF-36 and EQD5), irreversible damage, comorbid conditions, medication and adverse events. Hospital Santa Maria (Lisbon) and the Hospital Garcia de Orta (Almada) contributed to Reuma.pt/LES with 305 patients, 95,1% females, 80% Caucasians with a mean age of 45.5 ±14.9y. The mean age at diagnosis was 35.9 ±14.9y and the mean disease duration was 10.3 ± 7.3y. SLE Disease Activity Index (SLEDAI) at the first evaluation was 3,4 ± 3,8 and current accrual damage assessed by the Systemic Lupus International Collaborating Clinics (SLICC) was 0,7 ± 1,1. Hypertension was reported in 24% of the patients, diabetes in 8.8% and cardiovascular diseases in 11%. The vast majority of patients was treated with hydroxychloroquine (93.9%) and corticosteroids (prednisolone 44.6%, prednisone 12.4%, deflazacort 18.%). Immunosuppressive drugs were used in about half of the cases (azathioprine in 27%, methotrexate in 15.5%, cyclophosphamide in 7.4%, micophenolate in 5%) and to a lesser extent biological therapies (rituximab in 5.9% and belimumab in 0.98% of the patients). Conclusions Reuma.pt, is a very useful tool, that allows a more efficient patient follow-up, and standardized data collection, storage and analysis, with the ultimate objective of improving patient care and simultaneously scientific research in the field of SLE. Disclosure of Interest None Declared

An adaptive random search optimization algorithm is presented, which is found to be very efficient in dealing with non-linear constrained and unconstrained problems. The major differences relatively to previously reported algorithms are that variable, parameter dependent compression vectors are employed in the contraction of the search regions and that shifting strategies incorporating “wrong-way” moves are enforced. The algorithm was tested with 24 severe functions published in the literature. Results were compared with those obtained employing another random search method and with published work. The proposed algorithm is shown to be more robust and more efficient in what concerns the overcoming of difficulties associated with local optima, the sensitivity to search intervals and associated compression factors, the starting solution vector and the dependency upon the random number sequence. The results obtained reveal the adequacy of the algorithm for the optimization of a broad range of problems encountered in chemical engineering practice.