The Polish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Polish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach\u2019s alpha, interscale correlations, test\u2013retest reliability, and construct validity (convergent and discriminant validity). A total of 154 JIA patients (10.4% systemic, 50.0% oligoarticular, 24.7% RF-negative polyarthritis, 14.9% other categories) and 91 healthy children, were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Polish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

How Does Endothelial Permeability Affect the Development of Juvenile Idiopathic Arthritis? Vascular Endothelial Cadherin as a Promising New Tool Helpful in the Diagnostic Process

Introduction. Vascular endothelial cadherin (VE-cadherin) is a calcium-dependent protein essential for stabilization of the adherens junctions of the endothelial cells. Through vasculogenic mimicry, VE-cadherin may influence angiogenesis in synovial fibroblast-like cells. The soluble extracellular domain of VE-cadherin may be considered an indicator of endothelial dysfunction. Its potential as a diagnostic biomarker in rheumatic diseases, including juvenile idiopathic arthritis (JIA), needs to be investigated. Materials and Methods. The study group included 80 patients diagnosed with JIA. In 53 individuals, blood samples were obtained twice with an average interval of 102.4±4.6 days. Results from the study group were compared to 29 age- and sex-matched healthy children. Results. Serum levels of VE-cadherin were significantly higher in JIA patients than in healthy controls. In such comparison, VE-cadherin had 87.5% sensitivity and 69.0% specificity for the cutoff level 4.36 ng/ml (Youden index 0.56, area under the curve 0.724). VE-cadherin concentrations negatively correlated with the disease activity score. However, such finding may be a false result because of the downregulation of VE-cadherin induced by glucocorticosteroids. Conclusions. VE-cadherin may become a promising diagnostic biomarker of early stages of JIA. Its predictive significance may be decreased by utilization of glucocorticosteroids. A multicentre study including patients with other arthritides is recommended for further evaluation of this protein

The Potential Importance of MicroRNAs as Novel Indicators How to Manage Patients with Juvenile Idiopathic Arthritis More Effectively

Small, noncoding sequences of ribonucleic acid called microRNAs (miRNAs, miR) are functioning as posttranscriptional regulators of gene expression. As they draw increasing attention of rheumatologists, there is a growing body of evidence concerning specific molecules that may affect the long-term care of patients with inflammatory arthritides. Findings involving children with juvenile idiopathic arthritis (JIA) are still limited though. The aim of the study was to browse the available data on microRNAs which may be utilized as potential biomarkers helpful in diagnosing and monitoring JIA patients. The review contains a brief summary on the most studied sequences: miR-16, miR-125a-5p, miR-146a, miR-155, and miR-223. It is complemented with other miRNAs possibly relevant for JIA (miR-145, miR-23b, miR-27a, and miR-204) and discussion on challenges for using miRNAs in pediatric rheumatology (particularly, issues regarding specificity of biomarkers and measurements involving synovial fluid)

A Granulocyte-Specific Protein S100A12 as a Potential Prognostic Factor Affecting Aggressiveness of Therapy in Patients with Juvenile Idiopathic Arthritis

Background. Defining new prognostic biomarkers has become one of the most promising perspectives for the long-term care of patients with juvenile idiopathic arthritis (JIA). The new efficient indicators of disease activity and potential response to treatment are crucial in establishing new therapeutic plans in accordance with the “treat to target” strategy. One of the most studied proteins is called S100A12, which is an alarmin specific for granulocytes, considered as a marker of their activity. Materials and Methods. Study involved 80 patients diagnosed with JIA. Children with systemic subtype were not included in the study. In 53 cases, blood samples were obtained in two time points. Results from the study group were compared to 29 age- and sex-matched healthy individuals. Results. Serum S100A12 levels were higher in JIA than in healthy controls at the study baseline (11.67 ± 6.59 vs. 6.01 ± 2.33 ng/ml). There were no significant differences in S100A12 values between assessed subtypes of JIA. The highest concentrations were observed in patients within a disease flare. S100A12 levels were not dependent from using glucocorticosteroids. The studied protein appeared to be an efficient biomarker for JIA patients: 100% specificity as a diagnostic marker (cut-off level: 10.73 ng/ml) and 100% sensitivity as an indicator of exacerbations within a 3-month observation (cut-off level: 5.48 ng/ml). Conclusions. S100A12 may become an important factor influencing decisions on aggressiveness of JIA therapy. Further elaboration on the clinical algorithm is necessary for that protein to be included in everyday practice

Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome

Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E-selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p = 0.018) and E-sel (p = 0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p = 0.005), but not E-sel (p = 0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p = 0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release

Is it possible to predict a risk of osteoporosis in patients with juvenile idiopathic arthritis? A study of serum levels of bone turnover markers

Background: Low bone mineral density is a common finding in children with systemic connective tissue diseases, including juvenile idiopathic arthritis (JIA). The influence of the ongoing process of bone remodeling on the disease course merits further investigation. The aim of this study was to assess the clinical relevance of markers of bone turnover and their potential role as predictors of higher fracture risk and, by extension, risk of osteoporosis. Materials and Methods: Blood samples were collected from 59 patients diagnosed with JIA in order to determine serum levels of the following markers of bone turnover: Beta-Crosslaps, osteocalcin, bone alkaline phosphatase, osteoprotegerin and receptor activator for nuclear factor kappa-B ligand. The values were analyzed with laboratory parameters and results of dual X-ray absorptiometry (DXA). Results: Osteoprotegerin and bone alkaline phosphatase levels were age-dependent. Beta-Crosslaps values were significantly higher in patients with positive JADAS27 score (p=0.0410). Osteoprotegerin levels were higher in patients treated with biological agents than only with disease-modifying anti-rheumatic drugs (p=0.0273). There was no relation between markers of bone turnover and sex, DXA results, dosage of glucocorticosteroids and disease duration. Conclusions: The authors postulate performing DXA measurements every 6 months in patients with higher disease activity. The potential lower fracture risk in children with JIA within biological treatment needs further assessment. Age- and sex-adjusted reference rates of bone turnover markers need to be developed for Central European patients in order to assess individual values properly

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA. Methods This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013–December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to < 18 years; Cohort 2, 6 to < 12 years; and Cohort 3, 2 to < 6 years. Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated. Results Twenty-six patients (age range 2–17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUCtau) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; Cmax (ng/mL) was 47.0, 41.7, and 66.2, respectively. Ctrough, Cmin, and t1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to Cmax (Tmax) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed. Conclusions PK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program. Trial registration ClinicalTrials.gov: NCT01513902