Concentration of survivin in children with oligo- and polyarticular juvenile idiopathic arthritis (JIA): diagnostic and prognostic value-a single-center study.

AIM: The goal of the study was to assess the diagnostic and prognostic utility of survivin in patients with juvenile idiopathic arthritis (JIA). METHODS: Seventy children with JIA-59 newly diagnosed and 11 biologically treated (46 girls and 17 boys) aged 1.5-18 years and 29 healthy children as a control group, appropriately matched in terms of sex and age, were included in the study. The disease activity was established on the basis of the JADAS-27 criteria. The concentration of survivin was assessed by an ELISA test in serum and also 18 matched synovial fluid samples collected from patients with JIA. RESULTS: Children with JIA were divided according to the subtype of the JIA. In 65.7% of patients, oligoarthritis was diagnosed. The largest group comprised children of low disease activity (62.9%) according to JADAS-27. The serum concentration of survivin was significantly higher in children with JIA compared to the controls (p < 0.001). The concentration of survivin was higher among patients positive for anti-cyclic citrullinated peptide autoantibodies (ACPA) (p = 0.001). In all synovial fluid samples, the concentration of survivin was higher than in matched serum (p = 0.003). Serum survivin concentration was not significantly associated with radiological damage status or active synovitis assessed by joint ultrasonography. Survivin level was not significantly associated with disease duration time or treatment with TNF-α inhibitors in DMARD's non-responders. CONCLUSIONS: Survivin should be considered as a biomarker of joint inflammation helpful in the diagnosis of oligo- and polyarticular JIA and probably not dependent on treatment with TNF-α inhibitors.

Long-Term Treatment With TNF-Alpha Inhibitors Improves Bone Mineral Density But Not Vertebral Fracture Progression in Ankylosing Spondylitis.

The aim of this cohort study was to evaluate the long-term effects of TNF inhibitors (TNFis) on BMD and the incidence of vertebral fractures (VFxs) in patients with ankylosing spondylitis (AS). Consecutive patients with active AS with TNFi treatment duration up to 4 years with available DXA scans and spine X-rays were included. BMD (classified according to the WHO criteria for osteoporosis) of the hip and lumbar spine, the VFx (classified as a Genant score >1/>20% height loss), and radiological progression (modified stoke ankylosing spondylitis spinal score [mSASSS]) scores were obtained at baseline and at 4 years of TNFi treatment. Overall, 135 AS patients were included. At baseline, 40.1% of patients had low BMD of the hip and 40.2% of the lumbar spine. This decreased to 38.1% (p = 0.03) with low hip BMD and 25.3% (p < 0.001) of the lumbar spine BMD after 4 years of TNFi treatment. VFxs were present at baseline in 11.1% of the 131 patients, which increased to 19.6% after 4 years of TNFi treatment. A Genant score ≥2, was found at baseline in 3 out of 14 VFx (21.4%) patients, which increased to 7 out of 27 VFx (25.9%) patients after 4 years. All disease activity parameters-the ankylosing spondylitis disease activity scale, the C-reactive protein, the erythrocyte sedimentation rate, and the bath ankylosing spondylitis disease activity index-decreased significantly (p < 0.001). The mean radiological progression (n = 80) increased significantly from a median mSASSS of 4.0 (1.5 to 16.0) at baseline to 6.5 (2.1 to 22.9) after 4 years of TNFi treatment (p < 0.001). Despite the improvement in BMD and the decrease in disease activity, we still found new VFxs, an increase in severity in the number and grade of VFxs, and radiographic progression during 4 years of treatment with TNFis in AS patients with long disease duration. © 2019 American Society for Bone and Mineral Research.

The role of genetic analysis for predicting outcome of rheumatoid arthritis.

INTRODUCTION: Rheumatoid Arthritis (RA) varies from a mild to a severe, unremitting illness characterized by uncontrolled inflammation with consequent damage to cartilage and bone of joints. Individualized therapeutic approaches based on likely outcome would facilitate a personalized therapeutic approach. Areas covered: Genetics is known to contribute a significant component of the variability in RA outcome, estimated at 45-60%. A number of candidate gene studies have been associated with variability in radiologically assessed joint damage; however a more comprehensive genome wide analysis is required to more fully characterize the genetic basis of RA severity. Expert commentary: Genetic profiling of patient presenting with RA has the potential to aid stratification based on predicted prognosis, this would inform the clinical development of a personalized therapeutic approach. It will also result in the identification of novel mediators of tissue damage in RA.

Etanercept Increases Bone Mineral Density in Ankylosing Spondylitis, but Does Not Prevent Vertebral Fractures: Results of a Prospective Observational Cohort Study.

OBJECTIVE: Ankylosing spondylitis (AS) is characterized by chronic inflammation leading to ankylosis, but also to low bone mineral density (BMD) and vertebral fractures (VFx). Treatment with tumor necrosis factor-α blockers decreases inflammation and has shown to be effective in increasing BMD. We studied the effects of etanercept (ETN) on BMD and VFx in patients with AS after 2 years of treatment. Further, we studied changes in bone turnover markers and radiological damage. METHODS: Patients with active AS, treated with ETN for 2 years, were included. BMD lumbar spine and hip were measured at baseline and after 2 years, as well as radiological damage (modified Stoke Ankylosing Spondylitis Spinal Score with the addition of the thoracic spine), VFx (Genant method), and change in bone turnover markers. RESULTS: Forty-nine patients with AS were included. After 2 years of ETN, hip BMD increased by 2.2% (p = 0.014) and lumbar spine BMD by 7.0% (p < 0.001). The Bath Ankylosing Spondylitis Disease Activity Index decreased significantly (p < 0.001), as well as C-reactive protein and erythrocyte sedimentation rate (p < 0.001). Despite ETN therapy, the number of patients with VFx more than doubled (from 6 to 15 patients, p = 0.003). Also, the radiological damage increased significantly over time (from 12.1 to 18.5, p < 0.001); however, no significant change in bone turnover markers was found. CONCLUSION: This prospective longitudinal observational cohort study showed that after 2 years of ETN, BMD of the hip and spine increased significantly, but the number of patients with VFx and the severity of VFx increased as well. Besides that, radiological progression, including the thoracic spine, increased significantly. Thus, the favorable bone-preserving effect is accompanied by unfavorable outcomes on VFx and radiological damage.

Coorte Sarar: atividade de doença, capacidade funcional e dano radiológico em pacientes com artrite reumatoide submetidos à artroplastia total de quadril e joelho / Sarar cohort: disease activity, functional capacity, and radiological damage in rheumatoid arthritis patients undergoing total hip and knee arthroplasty

RESUMOObjetivos:A coorte Sarar é composta por pacientes portadores de artrite reumatoide (AR) e artrite idiopática juvenil (AIJ) submetidos a artroplastias de quadril e joelho no hospital Sarah-Brasília. O objetivo deste estudo foi avaliar fatores clínicos e laboratoriais associados à atividade de doença, capacidade funcional e dano radiológico em pacientes com AR, participantes dessa coorte.Métodos:Estudo transversal, com coleta de dados em revisão de prontuário.Resultados:Foram incluídos 32 pacientes, com tempo médio de início da doença de 240 meses. Dezenove pacientes foram submetidos a ATJ e 17, a ATQ. Foi encontrada correlação positiva entre dose máxima de metotrexato (MTX) durante a evolução e Clinical Disease Activity Index (CDAI) (R = -0,46, p = 0,011) e negativa com Simplified Erosion and Narrowing Score (SENS) (R = -0,58, p = 0,004). Valores de SENS foram maiores nos pacientes com fator reumatoide (FR) (p = 0,005) e anticorpo antipeptídeo cíclico citrulinado 3 (anti-CCP3) positivo (p = 0,044), nos com maiores títulos de FR (p = 0,037) e anti-CCP3 (p = 0,025) e menores nos pacientes com história familiar de AR (p = 0,009). Valores de HAQ foram maiores em pacientes mais idosos (p = 0,031). Na regressão linear múltipla, somente “dose máxima de MTX” e “história familiar” permaneceram com associação significativa com SENS (r2= 0,73, p < 0,001 para ambas as variáveis). No modelo que avaliou CDAI, apenas “dose máxima de MTX” permaneceu com associação significativa (r2 = 0,35, p = 0,016).Conclusão:Na coorte Sarar, fatores clínicos e laboratoriais estiveram relacionados à atividade de doença, capacidade funcional e dano radiológico, semelhantemente a estudos que avaliaram pacientes com menor tempo de doença.

ABSTRACTObjectives:The Sarar cohort consists of patients with rheumatoid arthritis and juvenile idiopathic arthritis who underwent hip or knee arthroplasties at hospital SARAH-Brasília. The objective of this study was to evaluate clinical and laboratory factors associated with disease activity, functional capacity and radiological damage in rheumatoid arthritis patients, participants in this cohort.Methods:Cross-secal study, with data collection achieved from medical records review.Results:Thirty-two patients were included, with a mean time of disease onset of 240 months. Nineteen patients underwent total knee and 17 total hip arthroplasty. There was a positive correlation between maximum dose of methotrexate and Clinical Disease Activity Index (R = −0.46, p = 0.011), and a negative one with Simplified Erosion and Narrowing Score (R = −0.58, p= 0.004). Simplified Erosion and Narrowing Score values were higher in patients with rheumatoid factor (p = 0.005) and anti-cyclic citrullinated peptide antibody 3 positivity (p = 0.044), in those with higher rheumatoid factor (p = 0.037) and anti-cyclic citrullinated peptide antibody 3 (p = 0.025) titers, and lower in patients with family history of rheumatoid factor (p = 0.009). Health Assessment Questionnaire values were higher in older patients (p = 0.031). In multiple linear regression, only “maximum dose of methotrexate” and “family history” remained with significant association with Simplified Erosion and Narrowing Score (r2 = 0.73, p < 0.001 for both variables). In the model evaluating “Clinical Disease Activity Index” only “maximum dose of methotrexate” remained significantly associated (r2 = 0.35, p = 0.016).Conclusion:In the Sarar cohort, clinical and laboratory factors were related to disease activity, functional capacity and radiological damage, similar to studies evaluating patients with lower disease duration.

Sarar Cohort: disease activity, functional capacity, and radiological damage in rheumatoid arthritis patients undergoing total hip and knee arthroplasty.

OBJECTIVES: The Sarar cohort consists of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) who underwent hip or knee arthroplasties at hospital Sarah-Brasília. The objective of this study was to evaluate clinical and laboratory factors associated with disease activity, functional capacity and radiological damage in RA patients, participants in this cohort. METHODS: cross-sectional study, with data collection achieved from medical records review. RESULTS: Thirty-two patients were included, with a mean time of disease onset of 240 months. Nineteen patients underwenttotal knee (TKA) and 17 total hip (THA) arthroplasty. There was a positive correlation between maximum dose of methotrexate (MTX) and Clinical Disease Activity Index (CDAI) (R = -0.46, p = 0.011), and a negative one with Simplified Erosion and Narrowing Score (SENS) (R = - 0.58, p = 0.004). SENS values were higher in patients with rheumatoid factor (RF) (p = 0.005) and anti-cyclic citrullinated peptide antibody 3 (anti-CCP3) positivity (p = 0.044), in those with higher RF (p = 0.037) and anti-CCP3 (p = 0.025) titers, and lower in patients with family history of RA (p = 0.009). HAQ values were higher in older patients (p = 0.031). In multiple linear regression, only "maximum dose of MTX' and "family history" remained with significant association with SENS (r(2) = 0.73, p <0.001 for both variables). In the model evaluating CDAI only "maximum dose of MTX" remained significantly associated (r(2) = 0.35, p = 0.016). CONCLUSION: In the Sarar cohort, clinical and laboratory factors were related to disease activity, functional capacity and radiological damage, similar to studies evaluating patients with lower disease duration.