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.

No radiographic wrist damage after treatment to target in recent-onset juvenile idiopathic arthritis.

Background: To evaluate radiographic progression of patients with new-onset juvenile idiopathic arthritis (JIA) in response to an early, tightly-controlled, treatment-to-target.

Methods: Patients with JIA participating in the BeSt-for-Kids-study, randomized to 3 treatment strategy arms, were eligible if at least 1 conventional wrist-radiograph was available. Bone damage as reflected by carpal length was assessed using the Poznanski-score.

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.

Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial.

Question: Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?

Methods: In a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation.

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.

Manipulative interventions for reducing pulled elbow in young children.

Background: Pulled elbow (nursemaid's elbow) is a common injury in young children. It often results from a sudden pull on the arm, usually by an adult or taller person, which pulls the radius through the annular ligament, resulting in subluxation (partial dislocation) of the radial head. It can also be caused by a fall or twist.

Interventions for cutaneous molluscum contagiosum.

Background: Molluscum contagiosum is a common skin infection that is caused by a pox virus and occurs mainly in children. The infection usually resolves within months in people without immune deficiency, but treatment may be preferred for social and cosmetic reasons or to avoid spreading the infection. A clear evidence base supporting the various treatments is lacking.

A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities.

Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration.

Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies.

A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: initial 3-months results of the BeSt for Kids-study.

Background: Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study.

Methods: Included patients were randomized to either: 1.

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.

Bone health of patients with juvenile idiopathic arthritis: a comparison between dual-energy X-ray absorptiometry and digital X-ray radiogrammetry.

Objectives: Juvenile idiopathic arthritis (JIA) affects bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) is the most widely used technique to determine BMD. Digital X-ray radiogrammetry (DXR) is a feasible method for determination of cortical BMD on hand radiographs.

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.

Patient-reported joint count in juvenile idiopathic arthritis: the reliability of a manikin format.

Objective: To evaluate the reliability of a manikin format, patient-reported joint count in juvenile idiopathic arthritis (JIA), and to detect changes in agreement at a second visit.

Methods: Patients with JIA aged 12-21 were asked to mark joints with active arthritis on a manikin before their regular clinic visit. The physician then performed a joint count without having seen the patient's assessment.

Automated determination of bone age and bone mineral density in patients with juvenile idiopathic arthritis: a feasibility study.

Introduction: Chronic inflammation combined with glucocorticoid treatment and immobilization puts juvenile idiopathic arthritis (JIA) patients at risk of impaired growth and reduced bone mineral density (BMD). Conventional methods for evaluating bone age and BMD are time-consuming or come with additional costs and radiation exposure. In addition, an automated measurement of bone age and BMD is likely to be more consistent than visual evaluation.

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.

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.

Cost of biologics in the treatment of juvenile idiopathic arthritis: a factor not to be overlooked.

Biologics are a promising treatment option for juvenile idiopathic arthritis (JIA) but drug costs are very high compared to conventional treatment. From a socioeconomic view the additional costs of new interventions should be weighed against their incremental health benefits compared to standard care. Therefore we evaluated data on cost-effectiveness of biologics in JIA.

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.

Efficacy of biological agents in juvenile idiopathic arthritis: a systematic review using indirect comparisons.

Objective: Over the past decade, the availability of biological agents for the treatment of juvenile idiopathic arthritis (JIA) has increased substantially. Because direct head-to-head trials comparing these agents are lacking, we indirectly compared their efficacy.

Methods: In a systematic review, all available efficacy data from randomised controlled trials performed in JIA with inclusion of biological agents were retrieved.

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.