C. G. S. Saad

Effective seroconversion and safety following the pandemic influenza vaccination (anti-H1N1) in patients with juvenile idiopathic arthritis.

Objectives: To assess the vaccine response in juvenile idiopathic arthritis (JIA) as an extension of previous observation of immunogenicity and safety of a non-adjuvanted influenza A H1N1/2009 vaccine in a large population of juvenile rheumatic diseases. Moreover, to assess the possible influence of demographic data, disease subtypes, disease activity, and treatment on immunogenicity and the potential deleterious effect of the vaccine in the disease itself, particularly in the number of arthritis and inflammatory markers. Methods: A total of 95 patients with JIA and 91 healthy controls were evaluated before and 21 days after vaccination, and serology for anti-H1N1 was performed by haemagglutination inhibition assay (HIA). Patient and physician visual analogue scales (VAS), Childhood Health Assessment Questionnaire (CHAQ), number of active joints, acute phase reactants, and treatments were evaluated before and after vaccination. Adverse events were also reported. Results: JIA patients and controls were comparable regarding mean current age (14.9 ± 3.2 vs. 14.6 ± 3.7 years, p = 0.182). After vaccination, the seroconversion rate was significantly lower in JIA patients compared to controls (83.2% vs. 95.6%, p = 0.008), particularly in the polyarticular subtype (80% vs. 95.6%, p = 0.0098). Of note, JIA subtypes, number of active joints, acute phase reactants, CHAQ, patient and physician VAS, and use of disease-modifying anti-rheumatic drugs (DMARDs)/immunosuppressive drugs were similar between seroconverted and non-seroconverted patients (p > 0.05). Regarding vaccine safety, no deterioration was observed in the number of active joints and acute phase reactants during the study period. Conclusion: Influenza A H1N1/2009 vaccination in JIA induces a lower but effective protective antibody response probably independent of disease parameters and treatment with an adequate disease safety profile.

LTBI screening in rheumatoid arthritis patients prior to anti-TNF treatment in an endemic area.

SETTING Recommendations for screening for latent tuberculous infection (LTBI) in patients eligible for anti-tumour necrosis factor (TNF) agents remain unclear in endemic regions. OBJECTIVE To evaluate the long-term efficacy of LTBI screening and treatment in patients with rheumatoid arthritis (RA) receiving TNF blockers. DESIGN A total of 202 RA patients were screened for LTBI before receiving anti-TNF treatment using the tuberculin skin test (TST), chest X-ray (CXR) and history of exposure to tuberculosis (TB). All subjects were regularly followed at 1- to 3-month intervals. RESULTS Eighty-five patients (42%) were treated with a single anti-TNF agent, while 117 patients (58%) changed anti-TNF agents once or twice. LTBI screening was positive in 66 patients, 44 were TST-positive, 23 had a history of TB exposure and 14 had an abnormal CXR. Exposure alone accounted for LTBI diagnosis in 14 patients with a negative TST. LTBI patients were treated with isoniazid (300 mg/day) for 6 months, and none developed TB. During follow-up, TST was repeated in 51 patients. Conversion was observed in 5; 3 were diagnosed with LTBI and 2 with active TB respectively 14 and 36 months after receiving anti-TNF treatment, suggesting new TB exposure. CONCLUSION LTBI screening and treatment before anti-TNF treatment is effective in endemic areas and reinforces the importance of establishing contact history for diagnosing LTBI in RA patients.

EARLIER ONSET AND BRAINSTEM INVOLVEMENT AS KEY FEATURES IN A BRAZILIAN NEURO-BEHCET'S DISEASE COHORT

Background Behçets disease (BD) is a multisystem disease in which central nervous system involvement – neuro-Behçets disease (NBD) – may strike young patients with devastating consequences. In this regard, early diagnosis and treatment is essential to prevent injury. Objectives This study aimed to analyze NBD clinical features compared to non-neurological BD in order to distinguish disease patterns. Methods A retrospective study was performed in 101 BD outpatients from a single tertiary center followed between 2011 and 2016. BD diagnosis was based on the 2014 International Criteria for Behçets Disease. Demographic, clinical and imaging features of 28 NBD patients were compared to 73 BD patients without neurological involvement. Results Earlier disease onset was found in NBD compared to BD (26.0±10.2 vs. 30.2±8.8 years, p=0.04). There were no differences between genders incidences, with a female predominance in both groups (64.3 vs. 72.6%, p>0.05). Over half of patients (53.6%) presented NBD as the first symptom and the mean time between diagnosis and NBD onset was 3.8±5.9 years. Uveitis was less frequent in NBD patients (25% vs. 47.9%, p=0.04), together with cutaneous disease (50% vs. 76.7%, p=0.01) and articular involvement (17.9% vs. 46.5%, p=0.01). Oral ulcers, genital ulcers, intestinal and vascular involvement frequencies were similar in both groups. Regarding NBD presentation, brainstem involvement was the most prevalent (67.9%), followed by central venous thrombosis (32.1%), aseptic meningitis (17.9%), stroke (3.6%) and peripheral neuropathy (3.6%). Most patients (82.1%) had a single neurological attack whereas relapsing disease was found in 18.5%. Conclusions Our study found an earlier disease onset in NBD patients and a lower frequency of ocular, cutaneous and articular involvement. Moreover, several patients may unfold the disease as NBD, with lack of other manifestations. In addition, brainstem lesions occurred in most patients. Recognizing these disease patterns might support to expedite NBD diagnosis. Disclosure of Interest None declared

FRI0453 The Increased Prevalence of Nafld Is Worrisome among Patients with Psoriatic Arthritis

Background Non-alcoholic fatty liver disease (NAFLD) affects 20–30% of general population and a wide range of 14–59% patients with cutaneous psoriasis (PsO). Psoriatic arthritis (PsA) has been linked to comorbidities including diabetes, arterial hypertension, dyslipidemia and metabolic syndrome (MetS) though data on NAFLD in PsA is lacking. In fact, in PsA, NAFLD has been evaluatedin only one Italian study affecting 28% patients. Objectives To evaluate the prevalence of NAFLD in our cohort of patients with PsA. Methods All patients with PsA regularly followed-up during a 6 month period at our outpatient rheumatology clinic were studied. They were evaluated byabdominal ultrasound (US) and NAFLD was defined in the presence of hepatic steatosis (US = Grades I to III).The occurrence of associated comorbidities, includingarterial hypertension, diabetes and dyslipidemia was recorded and the NCEP-ACT III criteria were applied to identify subjects with metabolic syndrome (MetS). DAS 28, BASDAI and ASDAS were used to assess PsA disease activity, while HAQ was performed to assess functional impairment. Students t, Chi-square and Fishers exact tests were performed for statistical analyses and P values ≤0.05 were considered significant. Results Fifty six PsA patients were initially enrolled, but 3 were excluded due to the presence of alcoholic cirrhosis in 2 and a positive serology for hepatitis C in 1. Among the remaining 53 patients, 26 were males and 27 females, with mean age = 54,8±13 yrs (27–76) and mean disease duration = 14,4±8,1 yrs (04–40). US revealed NAFLD in 33/53 (63%) patients with PsA, confirmed by liver biopsy in 2. Arterial hypertension, diabetes and dyslipidemia affected 81%, 42%, 75% of patients with NAFLD respectively (P<0.001). MetS was present in 58,5% (31/53) individuals, significantly more prevalent in patients with compared to those without NAFLD: 26/33 (78.8%) vs. 05/20 (25.0%), P<0.001, despite of gender. All disease activity indices (% patients with DAS28>2.6), mean BASDAI and mean ASDAS) and HAQ scores were similar among patients with or without NAFLD (55.6% vs 46.7%; 3.1 vs 3.7; 1.9 vs 2.3; 1 vs 0.9 respectively, P>0.05). Conclusions NAFLD is very common in our cohort of PsA patients occurring in over 2/3 regardless of disease activity and associated to MetS in most subjects, suggesting a relationship between these conditions. Moreover, screening for NAFLD inPsA patients is warranted in order to avoid increased overall liver morbidity. References Psoriatic arthritis: a systematic review, International Journal of Rheumatic Diseases 2010; 13: 300–317. Wenck et al. Journal of the European Academy of Dermatology, 2011. Candia et al. Journal of the European Academy of Dermatology, 2015. Di Minno et al. Arthritis Research & Therapy, 2012. Disclosure of Interest None declared

SAT0245 In VIVO Evidence of IL-17/IL-23 Axis Activation in Ankylosing Spondylitis Patients with Long-Term TNF Blockade: The Missing Therapy Target?

Background In spite of recent evidences regarding the relevance of IL-23/IL-17 axis in Ankylosing Spondylitis (AS) pathogenesis, there are no data on the long-term effect of anti-TNF therapy in this pathway and their possible correlation with treatment, clinical, laboratory and radiographic parameters. Objectives Investigate the influence of TNF-blockage in IL-23/IL-17 axis of AS patients. Methods Eighty-six AS patients, 47 with refractory active disease (BASDAI≥4) referred to anti-TNF therapy and 39 AS patients with BASDAI<4 (AS control group) were included. The AS active group was evaluated at baseline, 12 months and 24 months after TNF blockage and compared at baseline to the AS control group and to 47 healthy age- and gender-matched controls. Plasma levels of IL-17A, IL-22, TNFα, IL-23, PGE2 were measured. Radiographic severity and progression was assessed by mSASSS. Results At baseline, active AS patients presented higher IL-23 and PGE2 plasma levels compared to AS control group (p<0.001 and p=0.008) and to healthy controls (p<0.001 and p=0.02). After 24 months of TNF blockage, IL-23 and PGE2 remained elevated with higher levels compared to healthy group (p<0.001 and p=0.03) in spite of significant improvement in all clinical (ASDAS-CRP, BASFI, BASMI and ASQol, p<0.001) and inflammatory parameters (C-reactive protein and ESR, p<0.001). Further analysis of 27 anti-TNF treated patients that achieved good-response (ASDAS-CRP<2.1 with Δ≥1.1) at 24 months revealed that their IL-23 plasma levels were higher than healthy controls (p<0.001) and higher than 21 AS control group with similar disease activity (ASDAS-CRP<2.1),(p=0.01). No predictor for anti-TNF response or to radiographic progression was identified. In AS active group (n=47), there was a strong correlation between IL-23 and IL-17A at baseline (r=0.64, p<0.001), 12 months (r=0.47, p=0.001) and 24 months (r=0.61, p<0.001). IL-23 was also correlated with PGE2 at 12 months (r=0.45, p=0.001) and 24 months (r=0.33, p<0.05). No correlation was observed between NSAID, cytokines levels and radiographic progression (p>0.05). Conclusions This study provides novel data demonstrating that IL-23/IL-17 axis is not influenced by TNF blockage in AS patients despite clinical and inflammation improvement and NSAID intake. In this context, IL-23/IL-17 blockage emerges as potential additional target in AS patients. References Hreggvidsdottir HS, Noordenbos T, Baeten DL. Inflammatory pathways in spondyloarthritis. Mol Immunol 2014;57:28-37. Yeremenko N, Paramarta JE, Baeten D. The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis. Curr Opin Rheumatol 2014;26:361-370. Disclosure of Interest None declared

AB0655 Cross-Cultural Adaptation and Validation of The Behçet's Syndrome Activity Score (BSAS) to Brazilian Portuguese Language: Strong Correlation with Brazilian Behçet's Disease Current Activity form (BR-BDCAF)

Background Assessment of Behçets Syndrome (BS) activity has been a concern since a treat-to-target strategy may improve disease outcome. The Brazilian Behçets Disease Current Activity Form (BR-BDCAF) is currently validated for Brazilian Portuguese, however, it is completed by the physician. Developed originally in English, the Behçets Syndrome Activity Score (BSAS) is the first patient-reported assessment tool, which would be useful in clinical routine use and clinical trial evaluations. Objectives To perform a cross-cultural adaptation of the BSAS to Brazilian Portuguese language and to evaluate its reliability in a population of Brazilian patients with BS, comparing to BR-BDCAF as a gold standard pattern. Methods Brazilian Portuguese version of the BSAS, named BR-BSAS, was obtained according to established guidelines. Fifty-five BS patients, diagnosed according to the International Study Group for Behçets Disease criteria, were requested to complete the BR-BSAS. A rheumatologist performed the BR-BDCAF on the same visit. Fifteen patients were selected for a second visit two weeks later, and completed the BR-BSAS once again. Descriptive statistics, intraclass correlation coefficient, internal consistency were calculated to assess reliability and validity of BR-BSAS. Also, we used Pearson coefficient to analyze correlation between the two questionnaires (BR-BSAS and BR-BDCAF). Results In this study group, 65.3% were females, with a mean age of 45.6 (SD 13.0) years and a mean disease duration of 15.9 (SD 13.0) years. The test-retest reliability of BSAS presented a good level (ICC=0.839, 95% CI [0.596-0.943]). Internal consistency was also acceptable, with a Cronbachs alpha of 0.773. Mean BR-BSAS score (range 0-100) was 31,29 (SD 24,54) and mean BR-BDCAF score (range 0-12) was 3,41 (SD 2,34). A strong correlation between BR-BSAS and BR-BDCAF scores was found (r=0.750). Conclusions BR-BSAS may be used to assess disease activity in Brazilian BS patients, with a strong correlation between BR-BSAS and BR-BDCAF scores. As a self-reported measure, BR-BSAS may easier to use in clinical practice, adding a patient-derived outcome that may help to improve therapy management decision. Disclosure of Interest None declared

PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients.

SAT0146 BehÇEt´S Disease Activity: An Important Factor for Immunogenecity of Unadjuvanted Influenza A/H1N1 Vaccine

Background Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, there are no studies evaluating its possible influence on clinical manifestations in Behçet´s Disease (BD). Objectives To evaluate short-term safety and efficacy of influenza A/California/7/2009/H1N1-like virus single vaccination and the potential deleterious effect of the vaccine in BD patients compared to healthy controls. Methods Eighty-five BD patients and 85 gender/age-matched healthy controls were evaluated before and 21-days after vaccination with unadjuvanted influenza A/H1N1-like virus regarding seroprotection/seroconversion, factor increase in geometric mean titre (FI-GMT), C-reactive-protein (CRP) levels and side effects. Brazilian BD Current Activity Form (BR-BDCAF) was used to assess BD activity. Results Seroconversion rate was significantly lower in BD patients compared to controls (69 vs. 83%, p=0.04). Similar rates of seroprotection (71 vs. 83%, p=0.06) and FI-GMT (p=0.96) were found. Interestingly, BD patients without seroconversion had significantly higher mean BR-BDCAF scores (6.0 ±4.1 vs. 3.8 ±4.3, p=0.009), with a significantly increased rate of active BD in this group after the vaccination (73 vs. 50%, p=0.003). Disease duration and glucocorticoid, immunosuppressors or TNF-blockers therapies did not affect seroconversion (p>0.05). Regarding side effects, patients had significantly increased rate of mild and transient reactions, such as fever (7 vs. 0%, p=0.02), headache, (27 vs. 12%, p=0.02), arthralgia (24 vs. 0.2%, p<0.001) and myalgia (25 vs. 9%, p=0.004). Moderate and severe side effects were not reported. Conclusions This is the first study to indicate appropriate influenza A/H1N1 vaccine safety and efficacy in BD, reinforcing its recommendation. Disease activity impaired humoral response to vaccination. Further studies are necessary to determine if a second dose would increase seroconversion rates in these patients. References Fiore AE, Uyeki TM, Broder K, Finelli L, Euler GL, Singleton JA, Iskander JK, Wortley PM, Shay DK, Bresee JS, Cox NJ; Centers for Disease Control and Prevention (CDC). Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. Disclosure of Interest None Declared

SAT0268 Effect of long-term TNF blockage on lipid profile in ankylosing spondylitis patients

Background Ankylosing spondylitis (AS) patients have increased cardiovascular (CV) morbidity and mortality. Lipid profile plays an important role in development of CV disease and there are no data regarding prospective long-term evaluation of lipid profile in AS patients under TNF blockers.1 Objectives to evaluate prospectively the long-term effect of TNF blockage therapy on lipid profile in AS patients and its possible association with clinical and disease parameters. Methods Thirty-seven consecutive AS patients, who were eligible to receive anti-TNF therapy, were prospectively enrolled. All patients were treated with TNF blockers during the follow-up period, and they were evaluated for lipid profile, atherogenic index (AI), body mass index (BMI), waist circumference and disease parameters at baseline and at 52 and 104 weeks after treatment. Patients using statins or with concentration of LDL cholesterol >160 mg/dL were considered at risk.2 Data are expressed in means ± standard deviation or medians (interquartile ranges) as appropriate. For continuous variables, one-way Anova or Kruskal-Wallis analysis of variance was used with a significance level p<0.05. Results Evaluation of lipid profile during the follow-up period revealed a significant increase in levels of LDL cholesterol (98±27mg/dL vs. 109±30 mg/dL vs 117±33 mg/dL, p=0.029) and a trend for an increase in total cholesterol in the same period (168±33 mg/dL vs. 181±35 mg/dL vs. 187±39mg/dL, p=0.057). No changes were found in the concentration of HDL cholesterol (45 (37-58) mg/dL vs. 48 (42-61) mg/dL vs. 50 (43-59) mg/dL p=0.20) and triglycerides (93 (75-133) mg/dL vs. 88 (72-118) mg/dL vs. 95 (76-125) mg/dL p=0.84) or in AI (3.7±1.1 vs. 3.7±0.9 vs. 3.8±1.0 p=0.87) was observed. The proportion of patients considered at risk remained unchanged (5.5% vs. 13.5% vs. 16.2%, p=0.24). BMI (26.0±4.6 kg/m2 vs. 26.4±4.6 kg/m2 vs. 26.7±4.9 kg/m2, p=0.78) and waist circumference (89.7±12.6 cm vs. 92.1±12.2 cm vs. 94.1±12.7 cm, p=0.49) values remained stable throughout the study. Treatment with TNF blockers improved all disease parameters: BASDAI (p<0.001), BASFI (p<0.001), ASQoL (p=0.004), C-reactive protein (p<0.001), and erythrocyte sedimentation rate (p<0.001). Conclusions The novel demonstration that anti-TNF therapy has a long-term deleterious effect in LDL cholesterol levels in AS patients, reinforces the recommendation for a close monitoring and early intervention in this modifiable cardiovascular risk factor. References Bremander A, Petersson IF, Bergman S, et al. Population-based estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis. Arthritis Care Res (Hoboken) 2011;63:550–6. Lipsy RJ. The National Cholesterol Education Program Adult Treatment Panel III guidelines. J Manag Care Pharm 2003;9:2-5. Disclosure of Interest None Declared