Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti-Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy.

Objective: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA).

Methods: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued.

Pediatric Rheumatology Collaborative Study Group - over four decades of pivotal clinical drug research in pediatric rheumatology.

Importance: Specialized research networks are essential to achieve drug approvals for rare pediatric diseases. Such networks help realize the potential of global legislation enacted upon the recognition that most children are treated with drugs whose most beneficial dose and regimen have not been established in pediatric patients. The Pediatric Rheumatology Collaborative Study Group (PRCSG) is a North American clinical trials network that is specialized in the performance of clinical trials of new therapies for pediatric populations with rheumatic diseases.

Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease.

Objective: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease.

Methods: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months.

High Levels of DEK Autoantibodies in Sera of Patients With Polyarticular Juvenile Idiopathic Arthritis and With Early Disease Flares Following Cessation of Anti-Tumor Necrosis Factor Therapy.

Objective: The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemotactic factor. Abundant levels of DEK and DEK autoantibodies are found in inflamed synovium in JIA.

Predictors of Reduced Health-Related Quality of Life in Adult Patients With Idiopathic Inflammatory Myopathies.

Objective: Extensive studies on health-related quality of life (HRQoL) in idiopathic inflammatory myopathies (IIMs) are lacking. Our objective was to document HRQoL and to identify factors associated with a reduced HRQoL in patients with IIM.

Methods: A total of 1,715 patients (median age 49.

Lack of Concordance in Interrater Scoring of the Provider's Global Assessment of Children With Juvenile Idiopathic Arthritis With Low Disease Activity.

Objective: To measure agreement among raters when scoring the physician/provider global assessment (PGA) of disease activity in patients with juvenile idiopathic arthritis (JIA) with no apparent disease activity, and to identify clinical and laboratory parameters that most strongly influence provider scoring of the PGA.

Methods: Profiles of clinical and laboratory findings from 20 patients with JIA with no apparent disease activity were given to 51 providers, who were asked to score the PGA using a 21-circle visual analog scale (range 0-10). Following initial scoring, providers discussed each profile and reasons for assigning the score given, and then were asked to rescore each profile.

The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis.

Objective: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs).

Methods: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc.

The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis.

Objective: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs).

Methods: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc.

Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years.

Objective: The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease-modifying antirheumatic drugs were previously established in a phase III study that included a 4-month open-label lead-in period, a 6-month double-blind withdrawal period, and a long-term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient-reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup.

Methods: Patients enrolled in the phase III trial could enter the open-label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double-blind period.

The effect of rilonacept versus placebo on health-related quality of life in patients with poorly controlled familial Mediterranean fever.

Objective: To examine the effect of rilonacept on the health-related quality of life (HRQoL) in patients with poorly controlled familial Mediterranean fever (FMF).

Methods: As part of a randomized, double-blinded trial comparing rilonacept and placebo for the treatment of FMF, patients/parents completed the modified Child Health Questionnaire (CHQ) at baseline, and at the start and end of each of 4 treatment courses, 2 each with rilonacept and placebo.

Results: Fourteen subjects were randomized; mean age was 24.

Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the Phase 4 registry.

Background: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs).

Methods: Children aged ≥2 to <18 years with rheumatoid-factor-positive or -negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib.

Enhancing crossover trial design for rare diseases: limiting ineffective exposure and increasing study power by enabling patient choice to escape early.

Background: Addressing the two most important considerations in designing clinical trials, i.e. maximizing study power and minimizing patient exposure to ineffective treatment, is particularly challenging for trials of rare diseases.

Clinically inactive disease in a cohort of children with new-onset polyarticular juvenile idiopathic arthritis treated with early aggressive therapy: time to achievement, total duration, and predictors.

Objective: To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA).

Methods: Eighty-five children were randomized blindly to methotrexate (MTX), etanercept, and rapidly tapered prednisolone (MEP) or MTX monotherapy and assessed for CID over 1 year of treatment. Patients who failed to achieve intermediary endpoints were switched to open-label MEP treatment.

Advances from clinical trials in juvenile idiopathic arthritis.

Treatments available to children with juvenile idiopathic arthritis (JIA) have improved dramatically in the past 15 years, largely because of the development of powerful new biologic treatments. However, the seeds of this development were sewed over 40 years ago with the formation of a group of paediatric rheumatologists who understood the necessity of performing clinical trials in children with JIA. From there, international paediatric rheumatology networks have grown, and are dedicated to and highly experienced in performing such clinical trials.

Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis.

Objective: To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA).

Methods: In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase.

Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial.

Background: Currently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF.

Objective: To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF.

Algorithm development for corticosteroid management in systemic juvenile idiopathic arthritis trial using consensus methodology.

Background: The management of background corticosteroid therapy in rheumatology clinical trials poses a major challenge. We describe the consensus methodology used to design an algorithm to standardize changes in corticosteroid dosing during the Randomized Placebo Phase Study of Rilonacept in Systemic Juvenile Idiopathic Arthritis Trial (RAPPORT).

Methods: The 20 RAPPORT site principal investigators (PIs) and 4 topic specialists constituted an expert panel that participated in the consensus process.

Inactive disease and remission in childhood-onset systemic lupus erythematosus.

Objective: To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE).

Methods: Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR.

Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis.

Objective: To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months.

Methods: Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.

American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis.

Objective: To prospectively validate the preliminary criteria for clinical inactive disease (CID) in patients with select categories of juvenile idiopathic arthritis (JIA).

Methods: We used the process for development of classification and response criteria recommended by the American College of Rheumatology Quality of Care Committee. Patient-visit profiles were extracted from the phase III randomized controlled trial of infliximab in polyarticular-course JIA (i.

Preliminary criteria for global flares in childhood-onset systemic lupus erythematosus.

Objective: To develop widely acceptable preliminary criteria of global flare for childhood-onset systemic lupus erythematosus (cSLE).

Methods: Pediatric rheumatologists (n = 138) rated a total of 358 unique patient profiles with information about the cSLE flare descriptors from 2 consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-double-stranded DNA antibodies, disease activity index scores, protein:creatinine (P:C) ratio, complement levels, and erythrocyte sedimentation rate (ESR). Based on 2,996 rater responses about the course of cSLE (baseline versus followup), the accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve) of candidate flare criteria was assessed.

Clinical trial safety and mortality analyses in patients receiving etanercept across approved indications.

Objectives: Assessment of associations between etanercept treatment and rare adverse events has been limited by the size of clinical trial populations. The authors examined the collective safety of etanercept in clinical trials across approved indications.

Patients And Methods: Forty-nine U.

Measuring process of arthritis care: a proposed set of quality measures for the process of care in juvenile idiopathic arthritis.

Objective: The ability to assess quality of care is a necessary component of continuous quality improvement. The assessment typically is accomplished by determination of compliance with a defined set of quality measures (QMs). The objective of this effort was to establish a set of QMs for the assessment of the process of care in juvenile idiopathic arthritis (JIA).

The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial.

Background: We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA).

Methods: In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44.

Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis.

Objective: To evaluate the effects of long-term etanercept treatment, with or without methotrexate, on growth in children with selected categories of juvenile idiopathic arthritis (JIA).

Methods: We conducted a 3-year, open-label, nonrandomized registry of 594 patients with polyarticular or systemic JIA treated with etanercept only, etanercept plus methotrexate, or methotrexate only. Height, weight, and body mass index (BMI) were assessed at baseline and at years 1, 2, and 3, using percentiles derived from US Centers for Disease Control and Prevention standardized growth charts.