Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial.

Background: Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking.

Significant pain decrease in children with non-systemic Juvenile Idiopathic Arthritis treated to target: results over 24 months of follow up.

Background: The aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.

Methods: In the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients.

Patterns of clinical joint inflammation in juvenile idiopathic arthritis.

Objectives: We studied patterns of joint inflammation in juvenile idiopathic arthritis (JIA) to assess whether joint activity recurs locally in the same joints.

Methods: Joints of 91 patients of the BeSt for Kids study, a treat-to-target trial for children with recent-onset oligoarticular, rheumatoid factor-negative polyarticular and psoriatic JIA, were clinically assessed during 2 years (10 study visits). The association between joint inflammation at baseline and later inflammation in the same joint was assessed using a multilevel mixed-effects logistic regression model at joint level.

Nailfold capillary abnormalities in childhood-onset systemic lupus erythematosus: a cross-sectional study compared with healthy controls.

Objectives: For selection of high-risk systemic lupus erythematosus (SLE) patients it is necessary to obtain indicators of disease severity that predict disease damage. As in systemic sclerosis, nailfold capillary abnormalities could be such a biomarker in SLE. The primary objective of this cross-sectional study is to describe capillary abnormalities in childhood-onset SLE (cSLE) cohort (onset < 18 years) and compare them with matched healthy controls.

Update on the treatment of nonsystemic juvenile idiopathic arthritis including treatment-to-target: is (drug-free) inactive disease already possible?

Purpose Of Review: This review concerns the outcome for nonsystemic juvenile idiopathic arthritis (JIA) with emphasis on treatment-to-target (T2T) and treatment strategies aiming at inactive disease by giving an overview of recent articles.

Recent Findings: More efficacious therapies and treatment strategies/T2T with inactive disease as target, have improved the outcome for JIA significantly. Recent studies regarding treatment strategies have shown 47-68% inactive disease after 1 year.

MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis.

Objective: To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA.

Methods: Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months.

Psychometric Properties of the Pediatric Patient-Reported Outcomes Measurement Information System Item Banks in a Dutch Clinical Sample of Children With Juvenile Idiopathic Arthritis.

Objective: To assess the psychometric properties of 8 pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) item banks in a clinical sample of children with juvenile idiopathic arthritis (JIA).

Methods: A total of 154 Dutch children (mean ± SD age 14.4 ± 3.

Growth and Puberty in Juvenile Dermatomyositis: A Longitudinal Cohort Study.

Objective: To study growth and puberty in a multinational longitudinal prospective cohort of children with juvenile dermatomyositis (DM).

Methods: Children from 31 countries who were ages <18 years and had juvenile DM in active phase were studied, and analyses of height, weight, and pubertal development were conducted in those who had follow-up visits during a 2-year period and for whom anthropometric data was available.

Results: A total of 196 of 275 children (71%) were included.

Participation in a single-blinded pediatric therapeutic strategy study for juvenile idiopathic arthritis: are parents and patient-participants in equipoise?

Background: Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants.

The effect of repeated methotrexate injections on the quality of life of children with rheumatic diseases.

In clinical practice, the burden of repeated injections in children with rheumatic disease receiving disease-modifying anti-rheumatic drugs is significant. To investigate the nature and extent of impact on the quality of life after repeated injections, we conducted a literature review. Two relevant papers were identified, both about children with juvenile idiopathic arthritis (JIA) being administered methotrexate.

Identification of an Amino Acid Motif in HLA-DRβ1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis.

Objective: Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA, using a genome-wide association study in 522 children with JIA.

S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis.

Objective: Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response.

Methods: S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup.

MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis.

Introduction: Approximately 30% of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-TNF treatment. When clinical remission is induced, some patients relapse after treatment has been stopped. We tested the predictive value of MRP8/14 serum levels to identify responders to treatment and relapse after discontinuation of therapy.

Long-term quality of life and functional outcome of patients with juvenile idiopathic arthritis in the biologic era: a longitudinal follow-up study in the Dutch Arthritis and Biologicals in Children Register.

Objective: To carry out a longitudinal investigation of functional outcome, health-related quality of life (HRQoL) and treatment strategies in JIA patients who started etanercept >5 years ago.

Methods: We approached patients whose HRQoL changes were described previously in a subanalysis of the Dutch Arthritis and Biologicals in Children register. Recent disease status, co-morbidities and structural damage were retrieved.

Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register.

Background: Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999.

Objective: To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA.

Methods: The Arthritis and Biologics in Children register (multicentre prospective observational study) aimed to include all consecutive patients with JIA in the Netherlands who had started biological agents since 1999.

[Juvenile idiopathic arthritis: from biomarker to treatment].

Juvenile idiopathic arthritis (JIA) is the most common cause of chronic joint inflammation in childhood. The aetiology is unknown and the pathogenesis is multifactorial. JIA manifests itself in many various ways.

Low complement levels in paediatric systemic lupus erythematosus and the risk of bacteraemia.

This report describes an 11-year-old girl with systemic lupus erythematosus (SLE) with long-standing low levels of complement proteins. A disease period with lupus nephritis (class IIIa) was complicated by Staphylococcus aureus bacteraemia and osteomyelitis. She was treated with high-dose immunosuppressants and 6 weeks of high-dose intravenous antibiotics.

CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort.

Camptodactyly-Arthropathy-Coxa vara-Pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by mutations in PRG4 gene that encodes for proteoglycan 4, a mucin-like glycoprotein that is the major lubricant for joints and tendon surfaces. The molecular studies reported so far have described the identification of 15 mutations associated with this syndrome and the majority of them were found in families of Arabian origin. Here we report the molecular investigation of the largest European cohort that comprises 13 patients, and allowed the identification of 5 novel mutations and of the first case of CACP syndrome resulting from uniparental disomy of chromosome 1.

Treatment choices of paediatric rheumatologists for juvenile idiopathic arthritis: etanercept or adalimumab?

Objectives: To evaluate differences in baseline characteristics between etanercept- and adalimumab-treated JIA patients and to reveal factors that influence the choice between these TNF inhibitors, which are considered equally effective in the recent ACR recommendations for JIA treatment.

Methods: Biologic-naïve JIA patients with active arthritis who started treatment with adalimumab or etanercept between March 2008 and December 2011 were selected from the Dutch Arthritis and Biologicals in Children register. Baseline characteristics were compared.

Mesenchymal stromal cells isolated from children with systemic juvenile idiopathic arthritis suppress innate and adaptive immune responses.

Background Aims: Infusion of mesenchymal stromal cells (MSCs) has been reported to be an effective treatment modality for acute graft-versus-host disease, and MSCs have been considered for use in the treatment of patients with autoimmune diseases. Before contemplating clinical studies with MSCs in patients with systemic juvenile idiopathic arthritis (sJIA), the immunomodulatory capacity of MSCs in this setting needs to be explored. A comparative analysis of bone marrow-derived MSCs from children with sJIA and healthy pediatric controls was performed.

Tumour necrosis factor-blocking agents in persistent oligoarticular juvenile idiopathic arthritis: results from the Dutch Arthritis and Biologicals in Children Register.

Objective: Because TNF inhibitors are not approved for persistent oligoarticular JIA (oJIA), although they are used off-label, we evaluated their effectiveness in patients in this category.

Methods: Persistent oJIA patients were selected from the Dutch Arthritis and Biologicals in Children (ABC) register, an ongoing multicentre prospective study that aims to include all Dutch children with JIA using biologic agents. Response was assessed by the JIA core-set disease activity variables and modified Wallace criteria for inactive disease.

Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register.

Objective: To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure.

Methods: The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates.