Effect of an Electronic Pill Bottle on Hydroxychloroquine Adherence in Pediatric Lupus: Results of a Novel Direct-to-Family Pilot Trial.

Objective: The objective of this study was to evaluate the preliminary effectiveness of an electronic pill bottle with automated reminders on hydroxychloroquine (HCQ) adherence in children with pediatric systemic lupus erythematosus (pSLE).

Methods: This was a self-controlled, open label, direct-to-family pilot trial. Children with pSLE treated with HCQ were recruited from the Childhood Arthritis and Rheumatology Research Alliance Registry.

Pain Interference in Juvenile Idiopathic Arthritis.

Objective: Despite treatment advances, pain remains a serious problem for many children with juvenile idiopathic arthritis (JIA). To better understand pain in children with JIA and identify potentially modifiable factors, this study evaluated Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Pain Interference (PI) and its relationships with other pain measures and demographic, clinical, psychosocial, and functional variables.

Methods: This cross-sectional, observational, multicenter study used descriptive statistics and a mix of bivariate and multivariable analyses to describe PI and characterize relationships with other measures and variables.

Meeting report: patient and caregiver recommendations for a mobile health application for paediatric systemic lupus erythematosus.

Paediatric systemic lupus erythematosus (pSLE) management and research could be enhanced by a mobile health application (app); however, no app designed for pSLE is currently available. A development and design committee comprising of patients, parents/caregivers and other stakeholders met to inform development and design of an app specific for pSLE. This meeting report summarises the group's discussions and recommendations that could help create a useful and desirable app or mobile health tool for the pSLE community.

Atherosclerosis Progression in the APPLE Trial Can Be Predicted in Young People With Juvenile-Onset Systemic Lupus Erythematosus Using a Novel Lipid Metabolomic Signature.

Objective: Patients with juvenile-onset systemic lupus erythematosus (JSLE) have increased atherosclerosis risk. This study investigated novel atherosclerosis progression biomarkers in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, the largest investigator-led randomized control trial of atorvastatin versus placebo for atherosclerosis progression in JSLE, using carotid intima-media thickness (CIMT) as the primary outcome.

Methods: Unsupervised clustering of baseline CIMT and CIMT progression over 36 months was used to stratify patients with JSLE.

Meeting report: the ALPHA project: a stakeholder meeting on lupus clinical trial outcome measures and the patient perspective.

Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes.

Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.

Objective: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders.

Methods: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA.

Construct validity of Patient-Reported Outcomes Measurement Information System Paediatric measures in juvenile idiopathic arthritis and systemic lupus erythematosus: cross-sectional evaluation.

Objectives: Evaluate construct validity of Patient-Reported Outcomes Measurement Information System (PROMIS) Paediatric measures of symptoms and functioning against measures of disease activity among youth with juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE).

Design: Cross-sectional associations among PROMIS measures and clinical metrics of disease activity were estimated.

Setting: Seven clinical sites of the Childhood Arthritis and Rheumatology Alliance (CARRA) in the USA.

First-line options for systemic juvenile idiopathic arthritis treatment: an observational study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans.

Background: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) to compare treatment initiation strategies for systemic juvenile idiopathic arthritis (sJIA). First-line options for sJIA treatment (FROST) was a prospective observational study to assess CTP outcomes using the CARRA Registry.

Methods: Patients with new-onset sJIA were enrolled if they received initial treatment according to the biologic CTPs (IL-1 or IL-6 inhibitor) or non-biologic CTPs (glucocorticoid (GC) monotherapy or methotrexate).

Pharmacokinetics of hydroxychloroquine in paediatric lupus: data from a novel, direct-to-family clinical trial.

Objective: Determine the pharmacokinetics (PK) and exposure-response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).

Methods: We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months.

Pediatric rheumatologists' perspectives on diagnosis, treatment, and outcomes of Sjögren disease in children and adolescents.

Background: Sjögren disease in children and adolescents (pedSD) presents differently than adult disease. Diagnosis and classification are controversial, optimal treatment is unknown and outcomes are poorly understood. Here, we describe the current perspectives of pediatric rheumatologists on diagnosis, treatment, and outcomes of pedSD.

Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response.

To streamline drug development, the United States Food and Drug Administration (FDA) can consider the extrapolation of adult efficacy data to children when the disease and drug effects are sufficiently similar. This study explored whether the relationship between drug exposure and response for selected drugs in systemic lupus erythematosus (SLE) was sufficiently similar to support a consideration of the extrapolation of adult efficacy data to children of ≥5 years of age. An exposure-response analysis of drugs used to treat SLE was conducted using published exposure versus response and efficacy versus time data.

Disease Recapture Rates After Medication Discontinuation and Flare in Juvenile Idiopathic Arthritis: An Observational Study Within the Childhood Arthritis and Rheumatology Research Alliance Registry.

Objective: Children with well-controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare.

Methods: Children with JIA who discontinued conventional synthetic or biologic disease-modifying antirheumatic drugs for well-controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.

Urinary HER2, TWEAK and VCAM-1 levels are associated with new-onset proteinuria in paediatric lupus nephritis.

Objective: Lupus nephritis is a key driver of morbidity and mortality in SLE. Detecting active nephritis on a background of pre-existing renal damage is difficult, leading to potential undertreatment and accumulating injury. An unmet need is a biomarker that distinguishes active lupus nephritis, particularly important in paediatrics where minimising invasive procedures is desirable.

Self-Reported Health Outcomes of Children and Youth with 10 Chronic Diseases.

Objectives: To identify pediatric patient-reported outcomes (PROs) that are associated with chronic conditions and to evaluate the effects of chronic disease activity on PROs.

Study Design: Participants (8-24 years old) and their parents were enrolled into 14 studies that evaluated Patient-Reported Outcome Measurement Information System PROs across 10 chronic conditions-asthma, atopic dermatitis, cancer, cancer survivors, chronic kidney disease, Crohn's disease, juvenile idiopathic arthritis, lupus, sickle cell disease, and type 1 diabetes mellitus. PRO scores were contrasted with the US general population of children using nationally representative percentiles.

Feasibility and Efficacy of Online Strategies to Recruit Parents of Children With Rheumatic Diseases for Research.

Objective: We aimed to determine the feasibility and efficacy of online strategies to recruit parents of children with pediatric rheumatic diseases (PRDs) for research and to evaluate the degree to which known features of various rheumatic disease groups were present in the online cohort.

Methods: We studied two cohorts; the first was composed of respondents from a cross-sectional parental survey of children with PRDs contacted through patient support groups and social media platforms, and the second cohort was composed of participants from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) legacy clinical registry.

Results: In the social media cohort, 712 complete surveys were analyzed.

Cardiovascular Health in Pediatric Rheumatologic Diseases.

Cardiovascular disease risk is evident during childhood for patients with juvenile systemic lupus erythematosus, juvenile dermatomyositis, and juvenile idiopathic arthritis. The American Heart Association defines cardiovascular health as a positive health construct reflecting the sum of protective factors against cardiovascular disease. Disease-related factors such as chronic inflammation and endothelial dysfunction increase cardiovascular disease risk directly and through bidirectional relationships with poor cardiovascular health factors.

CARRA: The Childhood Arthritis and Rheumatology Research Alliance.

The Childhood Arthritis & Rheumatology Research Alliance (CARRA) launched in 2000 as a small network of pediatric rheumatologists and investigators dedicated to promoting collaborative research to improve the care and outcomes of childhood-onset rheumatic diseases. Over the past 2 decades, CARRA has grown to become a major driver of advances in evidence-based medicine and career development in pediatric rheumatology. Its research approach has transformed pediatric rheumatology.

Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans.

Objective: The optimal time to start biologics in polyarticular juvenile idiopathic arthritis (JIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated polyarticular JIA to compare strategies for starting biologics.

Methods: Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of 3 CTPs: 1) the step-up plan (initial nonbiologic disease-modifying antirheumatic drug [DMARD] monotherapy, adding a biologic if needed, 2) the early combination plan (DMARD and biologic started together), and 3) the biologic first plan (biologic monotherapy).