tbuckley/cabot-search huggingface dataset:
THU0558 Therapeutic response to prednisone according to the age in polymyalgia rheumatica: a controlled study
Authors: A Charpentier, F Verhoeven, M Sondag, X Guillot, C Prati, D Wendling
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder which usually affect patients over 65 years old. Different poor prognostic factors are involved in prednisone response including rapid decrease of prednisone dose or female sex. To date, there is no data relating the impact of the age on therapeutic response in PMR. <h3>Objectives</h3> The aim of this study was to compare, in case of PMR, the response to prednisone in patients younger than 60 to patients over 65 years old. <h3>Methods</h3> This was a retrospective, monocentric study. We included patients suffering from PMR, meeting ACR 2012 criteria. Patients were classified into two groups, one group with patients less than 60 years, and one group with patients over 65 years. We registered demographic, clinical, biological, and imaging data as well as therapeutic response profile. The local inflammation was evaluated with PET scan, by studying each anatomical site usually affected by PMR. Then, the rate of inflammation was scored from 0 to 3, according to the intensity of uptake compared to liver. The treatment was standardized. The initial dose of prednisone was of 0.3mg/kg/j during the two first weeks, then, the dose was slowly decreased by 10% each month. The main endpoint was a steroid dependence defined by the recurrence of PMR symptoms and/or the increase of CRP at two times during the decrease of prednisone. <h3>Results</h3> We included 14 patients younger than 60 years old (average age 54+/- 0.8 years) and 28 patients older than 65 years old (average age 75.8 +/- 1.5 years). The population younger than 60 years was mainly male (60% VS 27%, p&lt;0.05). Both groups were similar in terms of morning stiffness (2,1±0,4 VS 1,9±0,3 hours; p&gt;0.05), disease duration (4,2±0,8 VS 4,1±0,6 months; p&gt;0.05), leukocytes rate (8,3±1,37 VS 8±0,7 G/L; p&gt;0.05) and percentage of antinuclear antibodies rate over 1/320 (20% VS 10%; p&gt;0.05). However, regarding to local inflammation, the intensity of FDG uptake highlighted by the Pet scan was lower among young patients (score of 16,9±1,7 VS 26,5±3,0; p&lt;0.05). Furthermore, we observed a significant difference concerning therapeutic response according to the age: 60% of the young patients developed a steroid dependence compared to20% in group of old patients (p&lt;0.05). Moreover, the introduction of methotrexate was necessary for 35% of the young patients against 6.5% (p&lt;0.05). <h3>Conclusions</h3> Our study is the first to highlight the age as a bad prognosis factor in case of PMR. This difference is independent to the systemic inflammation and surprisingly, local inflammation (assessed by the TEP score) is more important in elderly people. Young patients suffering from PMR are mostly men and are more dependent on steroids. Thus, methotrexate could be straightaway proposed, particularly in patient younger than 60 years old. <h3>Disclosure of Interest</h3> None declared
AB0701 The real-life use of golimumab in patients with immune-mediated rheumatic diseases: one year results of the go-practice study
Authors: R-M Flipo, F Tubach, J Ouaniche, P Goupille, E Lespesailles, N Gouyette, P Bertin, B Fautrel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The GO-PRACTICE study was initiated to describe the use of Golimumab (GLM), a human anti-TNFα monoclonal antibody, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in French clinical practice. <h3>Objectives</h3> The primary objective of this interim analysis was to assess the persistence of GLM at 1-year. <h3>Methods</h3> Observational, multicenter, prospective, national study. Adult patients with RA, PsA and AS were included consecutively at GLM after the decision for GLM therapy has been taken or at least after GLM initiation, and followed-up for 2 years. We present here baseline characteristics for overall population (n=754) and interim results for patients with 1-year follow-up (n=228 patients with available data regarding persistence of GLM) <h3>Results</h3> A total of 754 patients (134 sites) were included between January 2015 and March 2016. Most of them had AS (64%), and 22% and 13% had RA and PsA, respectively. Mean age was 46±13 years and 61% were female. Almost 37% had received prior biotherapy. Nearly all patients (99%) were prescribed GLM as 50 mg-monthly injections. GLM was mostly co-prescribed with other antirheumatic treatments (84%). Of the 163 patients with available data at strictly 1-year, 56.4% were still treated with GLM; (61.9% in biotherapy-naïve patients); the persistence rate was similar across the three groups. The Kaplan-Meier duration curves of GLM are presented in figure 1. The main reason for GLM discontinuation was primary non-response, reported in 42% of patients. Among patients who continued GLM treatment, a meaningful improvement in disease activity was observed at 1-year in 71.9% of RA, 63.2% of PsA and 68.0% of AS patients. Patients-reported outcomes, including pain and functional disability, also showed improvement <h3>Conclusions</h3> In real-life practice in France, GLM was prescribed according to recommendations in terms of dosage and therapeutic strategy. One-year interim analysis, performed in one third of the cohort, suggests that GLM treatment is associated with clinical improvements leading to persistence of treatment. These results need to be confirmed in the final overall analysis planned in 2018. <h3>Disclosure of Interest</h3> R.-M. Flipo: None declared, F. Tubach: None declared, J. Ouaniche: None declared, P. Goupille: None declared, E. Lespesailles: None declared, N. Gouyette Employee of: MSD, P. Bertin: None declared, B. Fautrel: None declared
THU0463 Epidemiology of gout and hyperuricemia in new caledonia
Authors: T Bardin, E Magnat, P Clerson, P Richette, B Rouchon
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> New Caledonia is a Pacific island of 270.000 inhabitants with mixed ethnicities, including Melanesians (39.1%) and Polynesians (10.2%) and people from European ancestry (27.2%). <h3>Objectives</h3> To determine the prevalence of gout and hyperuricemia in the various ethnicities and to characterize associated factors. <h3>Methods</h3> A 3-degree random sample of the population aged 18 to 60 years old was redressed according to the 2014 New Caledonia census. Face-to-face interviews were performed by trained nurses who used a predefined questionnaire along with planned physical measurements. All participants underwent capillary measurement of creatinine level (StatSensor) and all men and only women older than 40 years underwent uricemia testing (HumaSens). Gout was defined by a validated algorithm (1). Hyperuricemia was defined by capillary level equivalent to plasma uric acid level (PUA) &gt;6 mg/dl (2) and/or urate lowering drug (ULD) prescription. <h3>Results</h3> 1.144 participants (mean age 37.7 years; 50.4% men) were included. Prevalence of gout in the entire redressed sample was 3.3% (95% CI 2.2–4.9). The prevalence was 4.1% (1.8–8.9), 2.6% (1.4–4.7), 6.7% (2.5–16.8), and 1.9% (0.5–6.6) for Europeans, Melanesians, Polynesians and other ethnicities, respectively. After adjustment for age and sex, Polynesians showed higher risk for gout than Europeans (adjusted odds ratio [aOR] 4.57 [95% CI 1.3–16.7]). Prevalence of hyperuricemia, determined in 658 participants, was 67.0% (95% CI 61.9–71.6). Prevalence of hyperuricemia was greater for Polynesians (aOR 9.17 [3.2–26.4]), Melanesians (aOR 4.02 [2.2–7.2]) and other ethnicities (aOR 2.18 [1.1–4.5]) than Europeans. On univariate analysis, factors associated with gout were hyperuricemia, male gender, age, BMI, waist circumference, renal failure, hypertension, diabetes, history of major episodes of depression and cancer but not dietary factors or physical activity, despite a consistent association with BMI. Among gout and non-gout patients, 45.9% and 0.7% were receiving ULT. Overall, 29.6% of patients receiving ULD had proper control of PUA levels (≤6 mg/dl). <h3>Conclusions</h3> As compared with Europe, in New Caledonia, the prevalence of gout and hyperuricemia was high, including in patients with European descent, as was previously reported for New Zealand (3). The prevalence of gout and hyperuricemia differed by ethnicity. For Melanesians, the prevalence of hyperuricemia was higher but risk of gout similar to that for Europeans, so factors (e.g., genetics) other than those involved in hyperuricemia may intervene in the risk of gout. <h3>References</h3> Richette et al. Ann Rheum Dis 2015;74:1684–90. Fabre et al ACR meeting, Washington 2016. Winnard et al Rheumatology 2012;51:901–9. <h3>Disclosure of Interest</h3> None declared
THU0370 Increased interleukin-17a concentration remains high in patients with ankylosing spondylitis treated with tumor necrosis α inhibitors within the year
Authors: IZ Gaydukova, A Rebrov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ankylosing spondylitis (AS) is associated with changes in the serum cytokines concentrations. During the treatment cytokines profile could change in different manner. <h3>Objectives</h3> The aim of the study was to evaluate the changes in concentration of interleukin-17A (IL-17A) in patients with AS, treated with tumor necrosis factor α inhibitors (anti-TNFα) during the year. <h3>Methods</h3> 30 patients with AS, fulfilled m. New-York criteria, with BASDAI ≥4.0 and NSAIDs non-responders were involved in the study. Mean age of AS patients at baseline was 38.35±9.19 years (M ± SD), the duration of AS was 11.4±9.6 years, 22 (73.3%) of patients – male. 20 healthy volunteers were involved as controls (mean age 40.1±7.7 years, male - 12 (60%). All AS patients were treated during the year with Remicade (infliximab, MSD®)) - 5 mg/kg at the recommended scheme. BASDAI, ASDAS<sub>CRP</sub> indices were calculated, C-RP, TNFα and IL-17A levels were measured before the treatment with anti-TNFα (baseline) and 52±2 weeks after the baseline. Number of patients achieved ASAS 20, ASAS 40 responses, and ASAS partial remission was evaluated. The statistics was performed with SPSS17. <h3>Results</h3> Baseline concentrations of TNFα and IL-17A in AS patients were higher than in healthy subjects (28.4±14.4 and 2.4±2.1, respectively, p&lt;0.000). Significant reduction of AS activity, but not of IL-17A serum concentration was marked at week 52, Table 1. 24 (80%) achieved ASAS 20, 18 (60%) – ASAS 40, 12 (40%) of patients with AS achieved ASAS partial remission. IL-17A was lower in patients who achieved remission compared to patients who did not achieve remission (figure). <h3>Conclusions</h3> Serum concentration of IL-17A remains stable in patients treated with anti-TNFα during the year. The baseline and final concentrations of serum IL-17A are higher in patients with AS who do not achieved ASAS partial remission compared to those who achieved the remission. <h3>Disclosure of Interest</h3> None declared
Abstract 307: Apoa-1 Binding Protein Regulates Retinal Angiogenesis via Control of Notch Signaling
Authors: Renfang Mao, Yury Miller, Longhou Fang
Journal: Circulation Research (2016)

ApoA-1 binding protein (AIBP), a mediator of cholesterol efflux from endothelia cells to HDL, plays a vital role in zebrafish angiogenesis. Although it is evolutionary conserved from Drosophila to human, its role of angiogenesis in higher vertebrate has not been studied. Thus, we propose that the role of AIBP in angiogenesis is also conserved from zebrafish to mice to humans. Mouse models display tremendous power in the study of human cardiovascular disease as the murine and human vasculatures are highly similar. We therefore generated Aibp -/- mice, which are viable and fertile. We then compared retinal vasculature development in Aibp -/- mice and wild-type control mice by whole mount immunostaining. Our data show that AIBP deficiency in mice results in significantly enhanced angiogenesis, including an increase in the radial extension of vascular plexus, the development of a denser upper capillary layer, and more tip cells as well as filopodia in the retinas. Notch signaling pathway plays an essential role for proper angiogenesis. However, the role of cholesterol metabolism in the Notch pathway is poorly understood. We found the expressions of the Notch downstream targets Hes1, Hey1 and Hey2 were upregulated in Aibp -/- retinas compared to controls. Furthermore, the protein level of Notch intracellular domain (NICD) was decreased in Aibp -/- retinas. These results suggest that the activity of Notch signaling is decreased in retinas from Aibp -/- mice. Mechanistically, we found AIBP positively regulates Notch signaling by affect on γ-secretase activity. Moreover, we performed Matrigel plug assay. Comparing that of wild-type, Matrigel plugs from Aibp -/- mice has more VE-cadherin staining and higher VE-cadherin mRNA expression level; and shows lower Hey1 expression as well as decreased NICD protein levels. It indicates that Matrigel plugs from Aibp -/- mice expresses more blood vessels and show lower Notch signaling activity. Our study demonstrated that AIBP inhibits angiogenesis by activating the Notch pathway and are the first to connect AIBP, a cholesterol metabolism regulator, to Notch signaling.
FRI0077 Gut commensals modulate inflammation via t regulatory cells
Authors: V Taneja
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Role of environmental factors in predisposition to develop rheumatoid arthritis (RA) have gained interest due, in part, to the studies showing an association of gut microbiota with immune homeostasis. Although the etiology of RA is unknown, recent studies on the role of gut microbiota in inflammatory adaptive immune response have led to the concept that interaction between the host microbiome and genetic factors influences autoimmunity. We have recently shown an association of Collinsella aerofaciens with RA <h3>Objectives</h3> In this study, we aimed to determine how human gut commensals modulate arthritis phenotype in humanized mice expressing RA-susceptible HLA-DQ8. <h3>Methods</h3> DQ8 mice following immunization with type II collagen develop arthritis and antigen-specific cellular and humoral response. DQ8 mice orally gavaged with RA-associated Collinsella aerofaciens and non-associated Prevotella histicola on alternate days for one week and were induced for arthritis. Gavage with microbes continued for 4 weeks. Mice were monitored for onset and progression of arthritis. Th17 regulatory network and cells involved in regulation were analyzed. DQ8 mice were gavaged with fecal homogenates supernatants from arthritis-resistant mice, induced for arthritis and monitored for disease. <h3>Results</h3> Mice gavaged with C. aerofaciens enhanced disease severity while P. histicola protected mice from arthritis. While treatment with <i>P. histicola</i> reduced intestinal permeability by increasing expression of tight junction proteins, C. aerofaciens had a complete opposite effect. Suppression of arthritis by P histicola was dependent on an increase in the numbers of CD103+ dendritic cells, myeloid suppressors, CD11b+Gr-1, and T regulatory cells, CD4+CD25+FoxP3+, in the gut as well as systemically. This led to reduction in TH17 response while increasing IL-10. On the other hand, C. aerofaciens gavage increased expression of IL-17 and regulatory chemokines as compared to controls. DQ8 mice gavaged with intestinal microbes of arthritis-resistant mice developed arthritis with lower incidence and had skewed Th17/Th2 response. <h3>Conclusions</h3> Our studies suggest that gut commensals influence immune response in and away from the gut. Commensals and their products may provide novel targets for therapeutic strategies in arthritis. <h3>Acknowledgements</h3> Funds were provided by the Department of Defense and Mayo Center of Individualized Medicine <h3>Disclosure of Interest</h3> None declared
THU0420 Improved survival of post-myocardial infarction patients treated with zofenopril combined with xantine oxidase inhibitors as compared to placebo or other ace-i
Authors: C Bentivenga, ER Cosentino, F Ventura, G Magri, I Ricci Iamino, S Bacchelli, E Ambrosioni, D Degli Esposti, N Malavolta, S Corvaglia, G Vukatana, C Borghi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). In these patients, use of sulfhydrylACE-inhibitors (ACEIs), such as zofenopril or captopril, and xanthine oxidase inhibitors (XOIs), may potentially result in an enhanced antioxidant effect and improved survival. However, the benefit of such combination in post-myocardial infarction has never been verified. <h3>Objectives</h3> To test the usefulness of the combination therapy Zofenopril + XOI in improving survival free from MACE in post-AMI patients <h3>Methods</h3> We re-analyzed the data of the four SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies by grouping patients according to the type of ACEIs and the use of XOIs. 165 (31.4%) of the 525 patients were treated with XOIs (79 under zofenopril and 86 under placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril and 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes). <h3>Results</h3> MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p=0.034 across groups). Rate of survival free from MACE was significantly larger in patients treated with zofenopril and XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06, 4.91), p=0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54, 2.64), p=0.669] or vs. placebo or other ACEIs combined with XOIs [1.82 (0.78, 4.26), p=0.169]. <h3>Conclusions</h3> Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an ACEI and urate lowering drug with antioxidant activity. <h3>Disclosure of Interest</h3> None declared
THU0579 Hypocomplementemia is related to elevated serum levels of IGG subclasses other than IGG4 in IGG4-related kidney disease
Authors: Y Fujisawa, I Mizushima, S Tsuge, S Hara, F Suzuki, K Ito, H Fuji, K Yamada, M Kawano
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> IgG4-related kidney disease (IgG4-RKD) is a comprehensive term for renal lesions associated with IgG4-related disease [1]. IgG4-RKD is frequently complicated by hypocomplementemia [1, 2, 3], but its clinical significance and mechanisms have not been clarified. <h3>Objectives</h3> This study aimed to investigate clinical features of IgG4-RKD patients with hypocomplementemia compared with those without it, leading to clarification of the clinical significance and mechanisms of hypocomplementemia. <h3>Methods</h3> We extracted 25 patients with IgG4-RKD between September 2005 and December 2016 in our hospital. Based on the presence/absence of hypocomplementemia at diagnosis, we divided them into a hypocomplementemia group (n=11) and normal complement group (n=14), and retrospectively analyzed various clinical features (age, sex, serum IgG levels, serum IgG4 levels, gaps between serum IgG and IgG4 level, ratio of serum IgG to serum IgG4, serum IgG subclasses, serum IgE levels, serum creatinine levels, urinary protein and urinary occult blood, urinary β2-microglobulin, urinary N-acetyl-β-D-glucosaminidase, initial dose of prednisolone, serum IL-2R levels, multiple organ lesion) during the clinical course in the two groups. <h3>Results</h3> The patients comprised 18 men and 7 women with an average age of 67.5 years (range, 44 to 81 years). Serum IgG levels (3971±729 mg/dL vs. 2157±598 mg/dL; p&lt;0.001), gaps between serum IgG and IgG4 level (2992±770 mg/dL vs. 1482±444 mg/dL; p&lt;0.001), serum IgG1 levels (2043±1025 mg/dL vs. 891±209 mg/dL; p=0.017), and the number of involved organs (4.1±1.1 vs 2.9±1.1; p=0.018) were significantly different between the two groups, while serum IgG4 levels (979±477 mg/dL vs. 791±575 mg/dL; p=0.298) and serum creatinine levels (1.96±1.89 mg/dL vs. 1.09±0.48 mg/dL; p=0.298) were not. At relapse of renal lesions, although both groups showed serum IgG4 re-elevation, the hypocomplementemia group showed exacerbation of hypocomplementemia and re-expansion of gaps between serum IgG and IgG4 level, while the normal complement group did not. <h3>Conclusions</h3> Hypocomplementemia may be associated with multiple organ involvement and elevation of IgG subclasses other than IgG4 including IgG1 in IgG4-RKD. In patients who initially show hypocomplementemia, a decline in serum complement levels implies renal lesion relapse. <h3>References</h3> Kawano M et al. Proposal for diagnostic criteria for IgG4-related kidney disease. Clin Exp Nephrol. 2011 Oct;15(5):615–26. Saeki T et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010 Nov;78(10):1016–23. Raissian Y et al. Diagnosis of IgG4-related tubulointerstitial nephritis. J Am Soc Nephrol. 2011 Jul;22(7):1343–52. <h3>Disclosure of Interest</h3> None declared