Araújo D

Toxoplasma gondii Isolates From Free-Range Chickens From the Northeast Region of Brazil

Abstract The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 152 free-range chickens (Gallus domesticus) from 22 municipalities in 7 northeastern states (Pernambuco, Rio Grande do Norte, Maranhão, Bahia, Ceará, Sergipe, and Alagoas) of Brazil was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT); 81 (53.3 %) chickens had titers of 1:5 in 26, 1:10 in 9, 1:20 in 4, 1:40 in 1, 1:80 in 6, 1:160 in 6, 1:320 in 13, 1:640 in 6, 1:1,280 in 3, 1:2,560 in 6, and 1:5,120 or higher in 1. Hearts and brains of 81 seropositive chickens were bioassayed individually in mice. Toxoplasma gondii was isolated from 23 chickens with MAT titers of 1:5 or higher; the isolates were designated TgCKBr165-187. Five isolates killed all infected mice. Results indicate widespread contamination of rural environment in Brazil with T. gondii oocysts.

DAS28, CDAI and SDAI cut-offs do not translate the same information: results from the Rheumatic Diseases Portuguese Register Reuma.pt

OBJECTIVES . The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients. Cut-off values were defined to classify the states of RA disease activity: remission, low, moderate and high. The aim of this work was to assess disease activity states classified by DAS28, CDAI and SDAI and to analyse their agreement in the Rheumatic Diseases Portuguese Register Reuma.pt. METHODS . A total of 2795 patients and 14 440 visits were selected from Reuma.pt for analysis. Pearsons correlation coefficients (PCCs) were calculated for the three indices. McNemars chi-squared tests, PCCs and kappa statistics were performed to analyse and compare the distribution of visits among all disease activity states and indices. RESULTS A strong correlation was found between the three indices throughout the 14 440 visits: r = 0.874 for DAS28/CDAI, r = 0.877 for DAS28/SDAI and r = 0.984 for CDAI/SDAI (all PCCs with P < 0.0001). However, when categorization in the different disease activity states was analysed, McNemars chi-squared tests and PCCs revealed significant disagreement between the cut-offs of the three indices. CONCLUSION DAS28, CDAI and SDAI cut-offs do not translate into the same clinical information in Reuma.pt. Although this might be expected for the original DAS28 cut-offs, when compared with CDAI and SDAI significant disagreement was also found for the DAS28 modified cut-offs. For visits where patients are in CDAI or SDAI remission, we also find disagreement between these two indices, which may contradict previous conclusions that acute phase reactants add little to composite disease activity indices for RA.

TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

A10.5 Comparative Effectiveness of Biological Therapies in Rheumatoid Arthritis is Influenced by Response Measures and Disease Activity State

Background and Objectives Several biological therapies have become available in the last years in the management of rheumatoid arthritis (RA). Two of the most common drug classes include anti-tumour necrosis factor (TNF) and anti-interleukin-6 (IL-6) agents, which target central cytokines in the disease pathway. We have previously shown that the proportion of patients achieving remission was higher in the tocilizumab group, an anti-IL-6 agent, compared to anti-TNF therapies, but the magnitude of the effect was associated with the disease activity measure used, namely DAS28, CDAI or SDAI. The aim of this study is to assess whether this difference remains significant in other RA disease activity states. Materials and Methods We included biologic-naïve RA patients registered in the Rheumatic Diseases Portuguese Register, Reuma.pt, who have started therapy with anti-TNF (adalimumab, infliximab, golimumab) and anti-IL-6 (tocilizumab) monoclonal antibodies after 1st January 2008. Our primary outcome was the proportion of patients in each disease activity state (remission, low, moderate, high) at 6 months, applying DAS28, CDAI and SDAI. Univariate and multivariate logistic regressions were performed to compare the groups. Results 220 RA patients were enrolled, 180 treated with anti-TNF monoclonal antibodies and 40 treated with tocilizumab. Both groups had similar baseline characteristics but tocilizumab-treated patients had significantly higher SJC, DAS28, SDAI and CDAI as well as shorter disease duration. At 6 months, a significantly higher proportion of patients in the tocilizumab group had reached the DAS28 (n = 21, OR 0.16, p < 0.0001, 95%CI 0.06–0.38) and SDAI (n = 9, OR 0.29, p = 0.03, 95%CI 0.09–0.91) remission thresholds, but no significant difference was seen for CDAI (n = 8, OR 0.41, p = 0.12), in the adjusted logistic multivariate model. Moreover, the proportion of patients with moderate (n = 85, OR 3.49, p = 0.006, 95%CI 1.44–8.43) and high disease activity (n = 30, OR 6.13, p = 0.028, 95%CI 1.32–30.89) was higher in the anti-TNF group only according to DAS28. No differences were seen in the low disease activity class. Conclusions Globally, tocilizumab-treated patients had better disease activity outcomes, but the magnitude of the effect was dependent on the disease activity measure used, confirming our previous results and underlining the pronounced reduction of inflammatory markers such as ESR and CRP, translated by lower DAS28 and SDAI, respectively. Furthermore, this effect was also related to the disease activity state considered. This may be explained by the fact that these different indexes distinctly weigh the different components and/or do not classify the same patients in the same disease activity state.

AB0802 Beliefs and treatment satisfaction in patients receiving biological agents

Background Treatment satisfaction represents an important outcome as it is related to adherence and willingness to continue treatment. Patients beliefs related to the medication (eg, about side effects and safety) also influence their satisfaction and, consequently, the treatment success. Satisfied patients are more likely to maintain a good relationship with a healthcare provider and report better health status1. Objectives To evaluate the beliefs and satisfaction of our patients with inflammatory rheumatic diseases with their current biological therapies. Methods Forty-one consecutive patients observed at our day-care unit completed an 18-item questionnaire concerning biological treatment. It included questions addressing their perceptions and satisfaction with their current treatment, information provided by their physician and about the knowledge and satisfaction regarding the cost of these therapies. The questionnaire was applied by the nurses to patients and blinded to provide anonymity. The attending physician was previously asked to record the disease state (remission/not remission) of each patient. Results We included 26 females and 15 males, with a mean age of 47.1±11.9 years. Forty six percent of the patients had rheumatoid arthritis, 27% psoriatic arthritis, 22% ankylosing spondylitis and 5% had undifferentiated spondylarthritis. Forty six percent of the patients were treated with etanercept, 29% with adalimumab, 13% with infliximab, 7% with rituximab and 5% with tocilizumab and 85.4% of patients were in clinical remission. Regarding the information provided by their doctor about the treatment, 95% of patients were satisfied, 97.6% responded that this treatment was effective to control the disease and 100% that their quality of life improved with this medication. Concerning safety, although 82.9% considered this drug safe, 56% responded that they had to take special care about their health, 22% believed to have more health complications and 14.6% experienced some side effects. Regarding convenience, 87.8% responded that their treatment frequency was convenient but 46.6% were unsatisfied with the form of administration and 24.4% reported that their treatment form/frequency interfered with their professional life. In relation to costs of the biologic agents,83% of patients considered that they are expensive and 98% didn’t agreed with the price. However when we tried to understand if patients had a correct notion of the cost, 73% of patients responded <1000 euros (€)/month, 46% <500 €/month and 22% said <100 €/month. Conclusions The majority of our patients were satisfied with the information provided by their doctor, considered the treatment effective in controlling the disease, reported improved in quality of life and considered them as safe drugs. In the negative perspective, we emphasize that 46.6% of patients are unsatisfied with the form of administration and 24.4% reported that it interfered with their professional life. Although most patients considered biological agents as expensive drugs, the majority underestimated their real cost, which reinforces the need for continuous education to raise the awareness of patients to avoid oversights/waste with the drug. References DiMatteo MR, Prince LM, Taranta A. Patient’s perceptions of physician’s behavior: determinants of patient commitment to the therapeutic relationship. J Community Health 1979;4:280-90. Disclosure of Interest None Declared

THU0454 Thyroid Involvement in Patients with Spondyloarthritis

Background The association between chronic inflammatory diseases and thyroid dysfunction is well recognized. This fact can be attributed to hormonal factors and the presence of a facilitator genetic terrain. Increased prevalence of Hashimoto’s thyroiditis (HT) has been described in rheumatoid arthritis, sjögren’s syndrome and systemic lupus erythematosus1. However, there are few data on the association of this disease in other chronic rheumatic disorders such as spondyloarthritis (SpA). Objectives To assess the prevalence of HT in a group of patients with SpA. Methods We included in this study 62 consecutive patients with SpA and 61 age-matched controls with osteoarthritis, primary osteoporosis or fibromyalgia. From January 2012 until January 2013, blood samples were drawn in all subjects. Thyroid-stimulating hormone, free triiodothyronine, free thyroxine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), titers of antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies were measured. The thyroid ultrasound was performed in all patients with changes in thyroid function tests. Age, gender, disease duration and medical treatments were collected. To assessdisease activity we evaluated the DAS 28 in peripheral SpA and the BASDAI in axial SpA. In the statistical analysis (chi-Square and student T-test for categorical and continuous variables, respectively), a significant association was considered if p<0.05. Results We found thyroid dysfunction in 12.9% of SpA and in 3.3% of controls (p<0.05). Hypothyroidism was more common than hyperthyroidism in both groups. We found anti-TG or anti-TPO positive in 16.1% of SpA and in 6.6% of controls (p=0.05) and the anti-TPO was the most frequent in both groups. The prevalence of HT (antibody positivity and ultrasonographic changes suggestive of thyroiditis) was higher in patients with SpA than in controls (9.7% vs 1.6% respectively, p<0.05). Among patients with SpA, HT was significantly more frequent in patients with peripheral involvement (83.3%) than in those with axial involvement (16.7%) and in patients with disease duration >5 years (p<0.05). Furthermore, patients treated with biologic therapy and those who were treated with ≥2 conventional DMARDs (in association) had significantly more HT (p<0.05). There was no association between subtype of SpA, actual ESR or CRP, the current DAS28 or BASDAI. Conclusions Our study demonstrates that HT occurs in patients with SpA with a higher prevalence than in controls, similarly as described in other chronic rheumatic diseases. Although we did not find association between HT with the current disease activity, the HT was significantly more frequent in patients with peripheral involvement, long disease duration and those treated with biological agents or with highest number of DMARDs. This suggests a possible relationship between HT and the maintenance of the inflammatory process in patients with SpA. These results suggest that thyroid function tests should be part of the clinical evaluation in patients with SpA. Currently, there is no clear explanation for the coexistence of these two diseases therefore further studies are needed to clarify the etiology of this association. References Chan T, Al-Saffar Z, Bucknall C. Thyroid disease in systemic lupus erythematosus and rheumatoid arthritis. Rheumatology 2001;40:353-4. Disclosure of Interest None Declared

THU0342 Neuropathic pain in patients with systemic sclerosis

Background Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs, pronounced alterations in the microvasculature and frequent cellular and humoral immunity abnormalities (1). In clinical practice, patients with SSc occasionally complain of pain in the extremities, such as dysesthesia, burning pain, and autonomic nervous symptoms (1,2).Few studies in SSc include assessments of pain. To date, there are no studies assessing the prevalence of neuropathic pain in SSc (2). Objectives To study the prevalence of neuropathic pain (NP) in the SSc patients and associations between SSc clinical variables and pain in all patients with SSc and in limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets Methods A total of 42 patients (36 females, 6 males) with a mean age 53.7±15.3 years, diagnosed according to American Rheumatism Association criteria for SSc were evaluated. Patients were classified into SSc subsets (lcSSc ordcSSc) according to the criteria for SSc by Leroy et al. Skin involvement was assessed with the modified Rodnan skin thickness score (MRSS) ranging from 0 to 51. The severity of Raynaud’s phenomenon was assessed with the number of patient-reported episodes in the past week. The severity disease was assessed by systemic sclerosis severity scale (SsSS) range from 0 to 36. The assessment of Hand Function was evaluated by Hand Mobility in SSc (HAMIS), range from 0 to 27 and the quality of life by Heath assessment questionnaire (HAQ). The neuropathic pain was evaluated by the DN4 neuropathic pain questionnaire. Using the DN4 neuropathic pain questionnaire, we divided patients into two groups: first group – patients with non- NP (0-3 points), second group - patients with NP (4-8 points). Results In SSc patients 67% (28 patients) had signs of NP by DN4. The prevalence of NP was higher in the patients who haddiffusecutaneous subsets. Patients with NP had longer disease duration (9.3±6.7years versus 3.8±2.3y, p<0.05) and a higher disease severity (15.3±9.2 versus 5.7±4.1 p<0,05). The modified Rodnan skin thickness score was higher in NP patients group (19.2±6.7 versus 8.6±4.6, p<0.01). The NP patients group had higher functional hand disability (12.6±9.6 versus 3.1±2.5 p<0.05). We found no significant differences between the two groups in quality of life andseverity of Raynaud’s phenomenon. NP presented with numbness 94%, tingling 92%, electric shocks 83%, painful cold 81%, burning 77% and itching 56% in the second group. In neurological examination 79% had hypoesthesia to pinprick and 72% had hypoesthesia to touch. Conclusions The pain syndrome in SSc is complex, because has multiples sources, with the neuropathic component prevailing in a 67% patients. SSc duration, skin thickness, diffuse cutaneous subsets and a disease severity had an impact in neuropathic severity, while severity of Raynaud’s phenomenon raynaud’s and HAQ is not linked to neuropathic pain. More attention to pain and how to best manage it is needed in SSc. References Valentini G. The assessment of the patient with systemic sclerosis. Autoimmun Rev 2003;2:370–6. Sokka T. Assessment of pain in patients with rheumatic diseases.Best Pract Res Clin Rheumatol 2003;17:427–49 Disclosure of Interest None Declared

AB0662 Flares in systemic lupus erythematosus: Etiology, outcome and prognostic factors

Background Lupus is a chronic, remitting and relapsing autoimmune disorder characterized by unpredictable disease flares and remissions. The rate and the severity of flares during course of treatment are important predictors of disease outcome. An essential part of treating patients with SLE is to try to keep the frequency and intensity of flares to a minimum. Objectives To determine the flare rate, etiology, outcome and prognostic factors for SLE flares. Methods One hundred and nine patients with SLE followed by our rheumatology department between 1995 and 2011 were eligible for the study. All patients included fulfilled ACR criteria for SLE. A flare was defined as (according to international consensus for a definition of disease flare in lupus) an increase in disease activity in one or more organ systems involving new or worsening clinical signs and symptoms and/or laboratory measurements. All pre-flare, flare, and post-flare visits were recorded with a SLEDAI score calculated for each visit. The flare rate was calculated by dividing the total number of flares in the cohort by the total follow-up years. We studied 109 patients, 106 female (97.2%) and 3 male (2.8%), with a mean age of 30.2±12.6 years at time of the diagnosis and 40.7±12.4 years in follow-up. In the statistical analysis (fisher exact test and student T test for categorical and continuous variables, respectively), a significant association was considered if p<0, 05. Results Seventy-eight of 109 patients (72%) had at least one flare. Thirty-one patients had more than one flare and 17 patients had 3 or more flares. The average number of flares/patient was 1.7±1.8 and the mean inter-flare time was 13.4±12.3 months. The flare rate in SLE was 0.52 flares/patient-year of follow-up. The median time to first flare from the date of diagnosis was 2.7±1.2 years. The average SLEDAI score during a flare was 11.8±4.2, at the pre-flare visit was 4.7±3.5 and post-flare visit was 5.3±2.7. The average SLEDAI score in the second flare was higher than first flare (13.7±4.4 versus 10,3±3,9, p=0,07), which reflects a bigger severity. The articular (n=47 patients) and renal flares (n=32 patients) occurred most frequently, followed by hematological (n=25 patients), cutaneous (n=17 patients), pericardium and pleural effusions (n=13) and neurological flares (n=5 patients). Patients with arthritis and cytopenia at the time of diagnosis had a significantly higher flare rate than those who did not (p<0, 05). Patients receiving continuous treatment with hydroxychloroquine and low dosis of corticosteroids had less and milder flares than patients without this treatment (p=0,001). In our cohort, infections (43%) and discontinuation of therapy (32%) were the main causes of flares. In 25% of the patients the flare etiology was undetermined. Conclusions In our cohort the flare rate in SLE was 0.52 flares/patient-year of follow-up. Most flares occurred in the first years of disease. The second flare was more severe than first. The articular and hematological involvements at time of diagnosis were more associated with flare rate than other organ involvement. This can be explained by the less intense immunosuppressive therapy in articular and hematological involvement. Continuous treatment with hydroxychloroquine and low dosis of corticosteroids decrease the number and severity of flares. Disclosure of Interest None Declared

THU0446 Evaluation of Fatigue in Patients with Spondyloarthritis

Background Fatigue is common to all the rheumatic conditions, in varying degrees, and is a frequent, often severe problem that has major consequences on patients life. Objectives To evaluate the fatigue in a group of patients with spondyloarthritis and possible associations with anemia, disease activity index and degree of pain with fatigue experienced by patients. Methods Patient’s demographic data were collected. The Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT F), version 4- Portuguese translation available, was applied for fatigue measurement. Scores range from 0 to 160, with lower scores reflecting greater fatigue. Patients were grouped by predominant axial or peripheral involvement. Clinical measures were collected according to the predominant involvement (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) for the axial and Disease Activity Score in 28 joints- erythrocyte sedimentation rate (DAS28- ESR) for the peripheral). In all, global assessment (PGA) of disease activity, pain on a 0-100-mm visual analog scale (VAS) and laboratory findings were recorded. Correlation studies were performed with Spearman test. Results A total of 51 patients were consecutively included, 32 (62.7%) were male and 19(37.3%) were female, with a mean age of 44.1±13.9 years (17 to 69) and a median disease duration of 137.6±110.1 months (7 to 445). The predominant involvement was axial in 28 (54.9%) patients and peripheral in 23 (45.1%). Nineteen (37.3%) patients were treated with biological therapies and 24 (47.1%) with classical disease-modifying anti-rheumatic drugs (DMARDs). Mean DAS28 was 2.41±1.26 (0.53 to 4.76) and BASDAI 2.78±2.43 (0 to 8.24), mean fatigue question in BASDAI of 3.03±2.98 (0 to 10) and mean BASFI was 3.31±2.89 (0 to 9.3). Mean of PGA and pain scores on a VAS was 31.51±25.44 and 32.57±29.1 respectively. FACIT-F scored from 61 to 158 (mean of 112.37±23.44). Mean FACIT-F was statistically significant lower in women than men (p<0.05) and the functional component of FACIT-F lower in patients with predominant peripheral involvement (p<0.05). Correlation with FACIT-F total score was strongest for BASFI (r= -0.710; p<0.01); BASDAI (r= -0.501; p<0.01); BASDAI-fatigue (r=-0.466; p<0.01), pain (r= -0.505; p<0.01), PGA (r=-0.455; p<0.01) and age (r=-0.404; p<0.01). DAS28, hemoglobin and ESR correlated with the physical component of the FACIT-F (r=-0.538; r=0.356; r=-0.382 with a p<0.05) but not with the total FACIT-F score. Fatigue levels were not significantly different between patients on biologic or other treatments. Conclusions Fatigue is an important symptom in patients with inflammatory arthritis. FACIT-F is a psychometrically sound measure of the fatigue in different domains. The FACIT-F showed a good (negative) correlation with measures of pain, disease assessment and disease function, showing a trend to be lower in patients with higher activity. No association was found with therapy, disease duration, acute-phase reactants or anemia. References Webster k, Cella D, Yost K. The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System: properties, applications, and interpretation. Health and Quality of Life Outcomes 2003, 1:79 Disclosure of Interest None Declared

Predictors of response and anti-TNF drugs comparative efficacy

Methods Analyses were performed upon Reuma.pt. Response to therapy was defined according to EULAR criteria. Probability of response was modeled. Multivariate logistic regression model predicting response over 1 year with all variables and automated stepwise selection models were built. In addition, we performed analyses using propensity score 1:1:1 nearest neighbor matching algorithms to obtain comparable groups regarding baseline features.