tbuckley/cabot-search huggingface dataset:
OP0196 Changing patterns of juvenile idiopathic arthritis patients treated with etanercept from 2000 to 2016 in the german biker registry population
Authors: G Horneff, K Minden, I Foeldvari, G Ganser, JP Haas, J Brunner, I Becker
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There is increasing experience with Etanercept (ETA) in juvenile idiopathic arthritis in the BIKER Registry. <h3>Objectives</h3> To report on practice changes ETA utilization and outcome over a period of 16 years. <h3>Methods</h3> 6 cohorts of pts were created according to inclusion period. Patients9 and disease characteristics,the utilization of DMARDs, steroids, NSAIDs were analysed. Efficacy was judged by PedACR30/50/70/90, JADAS and ACR-remission. <h3>Results</h3> Records from 2105 JIA pts treated with etanercept with at least a baseline and one follow up form were analysed. Most pts were females (67%). The median age of disease onset increased from 5.9 years in the early to 9.3 years in the later cohorts while age at start of treatment remained stable (about 13 years). Median disease duration markedly decreased from 5.3 to about 2 years. Most pts had RF neg. polyJIA followed by extended oligoarthritis. In the more recent cohorts the rate of enthesitis related arthritis increased and the rate f systemic JIA decreased (table). At registry start, 20% of newly enrolled pts belonged to the systemic JIA category compared to &lt;1% in 2016. During the study period, the overall utilization of glucocorticoids at baseline decreased from 54% to 19% (P&lt;0.0001), NSAID from 90% to 72% (P&lt;0.0001), MTX from 78% to 64% (P=0.004). ACR30/50%70/90 response rates at month 12 were 80%/74%/59%/40% and did not vary over time while the rate of patients reaching no active joint/CHAQ DI=0/JADAS-MDA/JADAS-Remission/ACR-Remission increased from 43%/35%/44%/19%/41% to 69%/48%/45%/26%/63%. <h3>Conclusions</h3> In recent years, children have been treated earlier, received less concomitant treatment with NSAIDS, corticosteroids as well as DMARDs. More recent cohort of patients had less severe disease at baseline, but also showed a markedly better outcome already at one year of treatment reflected by higher rates of patients with no active joint, a CHAQ DI of 0, a JADAS-MDA, and ACR-Remission. These data suggest that early disease control and better pre-selection of patients who need biologics are important to improve outcome and safety in children with JIA. <h3>Disclosure of Interest</h3> G. Horneff Speakers bureau: Abbvie, Pfizer, Roche, Novartis, MSD, K. Minden Speakers bureau: Abbvie, Pfizer, Roche, Genzyme, Pharm-Allergan, I. Foeldvari: None declared, G. Ganser: None declared, J. Haas: None declared, J. Brunner: None declared, I. Becker: None declared
FRI0394 Neuropathic pain is associated with skin thickness in systemic sclerosis patients
Authors: J Sousa-Neves, M Cerqueira, D Santos-Faria, J Leite Silva, C Afonso, F Teixeira
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic Sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of skin and internal organs, vasculopathy and systemic inflammation. To date, few studies assessed pain in SSc patients,(1) namely the neuropathic component. Data is also scarce on defining possible neuropathic pain (NP) predictors in these patients. <h3>Objectives</h3> To determine if patients with SSc have a higher prevalence of NP compared with a group of age and sex matched controls and study possible associations between NP and SSc clinical variables. <h3>Methods</h3> The study evaluated patients diagnosed with SSc fulfilling the SSc classification criteria of the American College of Rheumatology (ACR), older than 18 years old and followed up at our Rheumatology Unit. Forty-eight patients with mean age of 56.98±12.73 years and mean disease duration of 9.77±6.12 years were included. Comparison group comprised 45 age and sex matched controls. Patients and controls were consecutively evaluated at our Unit and NP in 4 questions questionnaire (DN4) was used for assessing the presence of NP. In SSc patients, skin involvement was also evaluated clinically by the modified Rodnan skin thickness score (mRSS) ranging from 0 to 51. Hand mobility (HAMIS) and SSc Severity Scale (SScSS) were also calculated and relevant clinical variables of the disease were collected. Parametric and nonparametric tests were used for comparative analysis. Multivariate logistic regression was used to identify factors associated to NP. Statistical significance was defined as P&lt;0.05. <h3>Results</h3> In our study, prevalence of NP assessed by DN4 was significantly higher in SSc patients comparative to controls (56.2% <i>versus</i> 13.3%, p&lt;0.001). In addition to age and sex, presence of diabetes (p=0.541) was also similar in both groups. In SSc group, patients with and without NP showed some statistically significant differences (table 1). Multivariate logistic regression revealed that only mean mRSS (odds ratio [OR] =1.90, 95% confidence interval [CI] 1.01 to 3.55, p=0.045) was independently associated with the presence of NP. <h3>Conclusions</h3> To the best of our knowledge, this is the first study evaluating the prevalence of NP in SSc patients in comparison with age and sex matched controls. NP was significantly more prevalent in patients with SSc. Skin thickness assessed by mRSS was independently associated with the presence of NP. <h3>References</h3> Schiei O et al. Prevalence, severity, and clinical correlates of pain in patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2010 Mar; 62(3):409–17. <h3>Disclosure of Interest</h3> None declared
FRI0381 Increased risk of osteoporotic fractures in adult patients with polymyositis and dermatomyositis: a nationwide population-based cohort study
Authors: C-C Lai, W-S Chen, Y-P Tsao, Y-S Chang
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with polymyositis and dermatomyositis (PM/DM) are characterized by chronic muscle weakness due to autoimmune-mediated myositis and are usually treated with corticosteroids initially. PM/DM patients prone to develop osteoporosis and subsequent fractures but are rarely investigated. <h3>Objectives</h3> To explore the incidence rate (IR) and risk factors of osteoporotic fractures (OFs) among adult PM/DM patients. <h3>Methods</h3> We conducted a cohort study by utilizing the Taiwan National Health Insurance database. PM/DM patients and respective age- and gender-matched cohort without PM/DM were enrolled. The primary endpoint was the initial event of OFs. We used the Cox proportional hazard model to study the risk factors of OFs in the PM/DM cohort. <h3>Results</h3> Among 2391 PM/DM patients (67.8% female, mean age: 49.5 years) followed for a mean (SD) of 6.1 (5.0) years, 116 developed vertebral fractures, 32 had hip fractures, and 14 experienced radius fractures (IR: 8.18, 2.20, and 0.96 per 1000 person-years, respectively, Table 1). Compared with the matched cohort, the PM/DM patients had higher IR ratios (IRRs) (95% CIs) of OFs at all age groups at enrollment: 3.27 (2.19 to 4.81, p&lt;0.0001) for people &lt;50 years and 2.29 (1.85 to 2.82, p&lt;0.0001) for those ≥50 years. The IRRs were 2.39 (1.92 to 2.94, p&lt;0.0001) for vertebral fractures and 1.62 (1.07 to 2.38, p=0.0093) for hip fractures. PM/DM patients experienced vertebral fractures and hip fractures at younger ages (62.2 vs 68.4 and 66.0 vs 75.4 years, respectively; both p&lt;0.001). Multivariable Cox regression analyses showed that being female gender, age ≥50 years, having hypertension, coronary artery disease, asthma, and using daily prednisolone equivalent to &gt;5 mg are associated with OFs. <h3>Conclusions</h3> Adult PM/DM patients had a high IR of vertebral and hip fractures. Patients who were female, advanced age, having certain comorbidities, and exposed to corticosteroid exhibited a higher risk. <h3>Disclosure of Interest</h3> None declared
SAT0292 Long-term prognosis and predicting factors of chinese patients with antiphospholipid syndrome
Authors: J Zhao, Y Sun, P Zhang, Q Wang, M Li, X Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antiphospholipid syndrome (APS) is an acquired autoimmune prothrombotic condition characterized by persistent circulating antiphospholipid antibodies (APL). The pathogenic mechanisms that lead to clinical manifestations associated with APL are only partially understood. And to date, long-term anticoagulation has been the only treatment shown to reduce vascular complications. <h3>Objectives</h3> The aims of the present study were to assess and identify the prognostic factors of the long-term outcomes and mortality of antiphospholipid syndrome (APS) in Chinese patients. <h3>Methods</h3> Records of 160 patients with APS admitted to Peking Union Medical College Hospital in Beijing between 2005 and 2015 were investigated. Demographic characteristics, cumulative clinical and laboratory features, autoantibody profiles were retrieved from the database. Survival rates were studied by Kaplan-Meier method, and COX proportional hazard model was adopted to perform the analysis of predicting factors for mortality. <h3>Results</h3> The entire cohort consisted of 110 (68.8%) female and 50 (31.3%) male patients. Mean (SD) age at study entry was 36.5±14.9 years. The most prevalent thrombotic risk factors were hypertension, dyslipidemia, and smoking, present in 5–15% of the total cohort. In total, 50.6% of the patients had primary APS, 45.9% had APS associated with SLE, 2.0% APS associated with other connective tissue diseases. The most prevalent immunological features at baseline were LA (71.3%), aCL (55.0%), and β2GPI (49.4%). No significant statistical differences were found in the clinical presentation of the APS according to the presence or absence of any of these antibodies. During the 10-year period, 16 (10.0%) patients (8 female and 8 male) died. The overall 1, 3, and 5-year survival rate was 92.6%, 89.1% and 87.1%, respectively. The most common causes of death were severe thrombotic events, including pulmonary embolism, strokes and myocardial infarction (43.8% of total deaths), infections (18.8%). COX proportional hazard model show thrombocytopenia is the independent prognostic factor of mortality (HR 8.228, 95% CI 1.866–36.282). <h3>Conclusions</h3> patients with APS develop significant morbidity and mortality despite current treatment. More attention should be devoted to APS patients with thrombocytopenia. <h3>Disclosure of Interest</h3> None declared
THU0562 Inflammatory joint disease triggered by immune checkpoint inhibitors
Authors: L Tucker, S Sacks, H Al-Mossawi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Immune checkpoint modulation has changed the cancer therapy landscape in recent years [1]. Randomised controlled trials now demonstrate superiority to standard chemotherapy in squamous cell lung cancer, renal cell cancer [2], squamous cell head and neck cancer [3] and malignant melanoma [4]. However, blockade of these checkpoints results in a multitude of autoimmune sequelae including joint disease. As these therapies become first-line in oncology, they will likely place a significant burden on rheumatology services. <h3>Objectives</h3> To establish the prevalence of rheumatological manifestations of checkpoint blockade in a non-trial standard care setting. <h3>Methods</h3> All patients treated with Nivolumab or Ipilimumab (as single agent or in combination) in a standard care setting within a single centre were included and the number of suspected cases with rheumatological manifestations identified from the case records. <h3>Results</h3> 75 patients have been treated with Nivolumab single agent and 12 with combination Nivolumab plus Ipilimumab in Oxford over the last 15 months. Within that cohort, there were 7 suspected cases of joint disease giving a potential prevalence of 8%. Of those 7, 2 had confirmed disease requiring therapy, both had received Nivolumab/Ipilimumab combination. Both cases were rheumatoid factor and CCP negative. One case responded to prednisolone only, while the second case was refractory to steroids, methotrexate and infliximab but responded to IL-6 blockade with Tocilizumab. <h3>Conclusions</h3> We observed an approximate 8% prevalence of checkpoint mediated autoimmune joint disease within a relatively short follow up period of 15 months. The longer-term prevalence may be higher. Both patients requiring therapy had been exposed to Ipilimumab suggesting the inflammatory joint toxicity with this agent may be higher than that caused by Nivolumab. Checkpoint immunotherapy is set to become the first-line standard of care in a number of cancers. This will lead to an increased demand for rheumatology services. The rheumatology community needs to develop strategies and trials in order to classify and treat these patients appropriately. <h3>References</h3> Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011; 480:480–9. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. NEJM. 2015; 373:1803–1813. Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. NEJM. 2016; 375:1856–1867. Larkin J, Chiaron-Sileni V, Gonzalez R et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015; 373:23–34. <h3>Disclosure of Interest</h3> None declared
Dynamic DNA methylation reconfiguration during seed development and germination
Authors: Taiji Kawakatsu, Joseph R. Nery, Rosa Castanon, Joseph R. Ecker
Journal: Genome biology (2017)

Unlike animals, plants can pause their life cycle as dormant seeds. In both plants and animals, DNA methylation is involved in the regulation of gene expression and genome integrity. In animals, reprogramming erases and re-establishes DNA methylation during development. However, knowledge of reprogramming or reconfiguration in plants has been limited to pollen and the central cell. To better understand epigenetic reconfiguration in the embryo, which forms the plant body, we compared time-series methylomes of dry and germinating seeds to publicly available seed development methylomes. Time-series whole genome bisulfite sequencing reveals extensive gain of CHH methylation during seed development and drastic loss of CHH methylation during germination. These dynamic changes in methylation mainly occur within transposable elements. Active DNA methylation during seed development depends on both RNA-directed DNA methylation and heterochromatin formation pathways, whereas global demethylation during germination occurs in a passive manner. However, an active DNA demethylation pathway is initiated during late seed development. This study provides new insights into dynamic DNA methylation reprogramming events during seed development and germination and suggests possible mechanisms of regulation. The observed sequential methylation/demethylation cycle suggests an important role of DNA methylation in seed dormancy.
THU0400 Risk factors of sagittal translation after pedicle subtraction osteotomy on ankylosing spondylitis
Authors: Y-S Park, J Kim, J-S Park
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Few studies on sagittal translation and its risk factors after pedicle subtraction osteotomy (PSO) in ankylosing spondylitis (AS) patients have been conducted. There is also no study on overall evaluation of radiologic parameters as the candidate of its risk factor. <h3>Objectives</h3> The aim of this study was to report the cases of sagittal translation which developed after PSO in AS patients with kyphotic deformity and to analyze its risk factors <h3>Methods</h3> The subjects of this study were 53 AS patients (58 cases) who underwent PSO to correct their kyphotic deformity between March 2006 and August 2016. The 53 subjects consisted of 45 males and 8 females. Their mean age was 39.3 12 Tit9&gt;7.9 (range: 29–67). After osteotomy, the patient was examined for the presence of sagittal translation in the correction site through intraoperative radiograph. The low modified Stoke AS spine score (mSASSS) was measured before the surgery. The vertebral parameters such as lumbar lordosis angle, thoracic kyphotic angle, and sagittal vertical axis, and the pelvic parameters such as pelvic incidence, pelvic tilt, and sacral slope were also measured before and after the surgery. The subjects were grouped according to the presence and absence of sagittal translation, and their radiologic parameters were compared. In addition, the correlation between sagittal translation and each parameter was analyzed. Complications that developed during and after the surgery were also analyzed. <h3>Results</h3> Sagittal translation developed in 16 subjects (30%) or 17 cases (29.3%). The mean lumbar lordosis angle and the mean sagittal vertical axis of both the sagittal translation (ST) group and the non-sagittal translation (Non-ST) group were successfully corrected (p=0.000, respectively). A significant difference in preoperative mean sacral slope was observed between the groups (p=0.045). The ST group showed a significantly higher mSASSS (48.1±20.7) than the Non-ST group (36.8±16.2) (p=0.002). In the multivariate regression analysis, sagittal translation was positively correlated with mSASSS (odds ratio 1.34, P=0.002) and the preoperative sacral slope (odds ratio 1.46, P=0.009), and negatively correlated with the difference between preoperative and postoperative thoracic kyphotic angle (odds ratio 0.68, P=0.01). Both groups showed no finding of permanent neurologic complication after the surgery. <h3>Conclusions</h3> The incidence of sagittal translation after pedicle subtraction osteotomy was closely related with the severity of ankyloses in AS patients. Therefore, when pedicle subtraction osteotomy is performed for AS patients with severe ankyloses and high sacral slope, it is required that surgeon consider sagittal translation which could induce neurologic complication. <h3>Disclosure of Interest</h3> None declared
Nivolumab Exposure–Response Analyses of Efficacy and Safety in Previously Treated Squamous or Nonsquamous Non–Small Cell Lung Cancer
Authors: Yan Feng, Xiaoning Wang, Gaurav Bajaj, Shruti Agrawal, Akintunde Bello, Brian Lestini, Friedrich Graf Finckenstein, Jong-Soon Park, Amit Roy
Journal: Clinical Cancer Research (2017)

Purpose: Nivolumab is a fully human IgG4 monoclonal antiprogrammed death-1 antibody with demonstrated efficacy, including durable responses and prolonged survival, in patients with previously treated, advanced non-small cell lung cancer (NSCLC). Exposure-response (E-R) analyses for efficacy and safety were conducted to inform the benefit-risk assessment of nivolumab in this patient population.Experimental Design: The analyses used clinical trial data from patients with squamous (n = 293) or nonsquamous (n = 354) NSCLC from four clinical trials who received nivolumab doses of 1 to 10 mg/kg every 2 weeks. E-R efficacy analyses were performed by investigating the relationship between time-averaged nivolumab concentration after the first dose (Cavg1) and the probability of overall survival by histology. E-R safety analyses examined relationships between nivolumab Cavg1 and hazards of adverse events leading to discontinuation or death (AEs-DC/D).Results: Nivolumab exposure was not associated with overall survival [the 95% confidence interval (CI) of effect included 1] in patients with squamous (HR, 0.802; 95% CI, 0.555-1.16) or nonsquamous NSCLC (HR, 0.94; 95% CI, 0.683-1.29). Similarly, nivolumab exposure was not associated with AEs-DC/D in the overall population (HR, 0.917; 95% CI, 0.644-1.31). The risk of AEs-DC/D was similar among patients with squamous or nonsquamous histology.Conclusions: Nivolumab monotherapy demonstrated a wide therapeutic margin, as evidenced by relatively flat E-R relationships over the range of exposures produced by doses of 1 to 10 mg/kg every 2 weeks (Q2W), supporting the use of the initially approved dose of 3 mg/kg Q2W in patients with NSCLC. Clin Cancer Res; 23(18); 5394-405. ©2017 AACR.
Guideline Recommendations for Statin Therapy—Reply
Authors: Neha J. Pagidipati, Ann Marie Navar, Michael J. Pencina
Journal: JAMA (2017)

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Long-Term Endothelial Cell Loss in Patients with Artisan Myopia and Artisan Toric Phakic Intraocular Lenses
Authors: Soraya M.R. Jonker, Tos T.J.M. Berendschot, Annick E. Ronden, Isabelle E.Y. Saelens, Noël J.C. Bauer, Rudy M.M.A. Nuijts
Journal: Ophthalmology (2017)
Antihyperglycemic Medications: A Claims-Based Estimate of First-line Therapy Use Prior to Initialization of Second-line Medications
Authors: Yi-Ju Tseng, Gregory Steinberg, Kathe P. Fox, Joanne Armstrong, Kenneth D. Mandl
Journal: Diabetes Care (2017)

OBJECTIVE The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes. However, nonadherence to antihyperglycemic medication is common, and a clinician could confuse nonadherence with pharmacologic failure, potentially leading to premature prescribing of second-line therapies. We measured metformin use prior to second-line therapy initialization. RESEARCH DESIGN AND METHODS This retrospective cross-sectional study used unidentifiable member claims data from individuals covered from 2010 to 2015 by Aetna, a U.S. health benefits company. Beneficiaries with two physician claims or one hospitalization with a type 2 diabetes diagnosis were included. Recommended use of metformin was measured by the proportion of days covered over 60 days. Through sensitivity analysis, we varied estimates of the percentage of beneficiaries who used low-cost generic prescription medication programs. RESULTS A total of 52,544 individuals with type 2 diabetes were eligible. Of 22,956 patients given second-line treatment, only 1,875 (8.2%) had evidence of recommended use of metformin in the prior 60 days, and 6,441 (28.0%) had no prior claims evidence of having taken metformin. At the top range of sensitivity, only 49.5% patients could have had recommended use. Patients were more likely to be given an additional second-line antihyperglycemic medication or insulin if they were given their initial second-line medication without evidence of recommended use of metformin (P &amp;lt; 0.001). CONCLUSIONS Despite published guidelines, second-line therapy often is initiated without evidence of recommended use of first-line therapy. Apparent treatment failures, which may in fact be attributable to nonadherence to guidelines, are common. Point-of-care and population-level processes are needed to monitor and improve guideline adherence.