Overlap of International League of Associations for Rheumatology and Preliminary Pediatric Rheumatology International Trials Organization Classification Criteria for Nonsystemic Juvenile Idiopathic Arthritis in an Established UK Multicentre Inception Cohort.

OBJECTIVE: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile idiopathic arthritis (JIA). METHODS: Participants from the Childhood Arthritis Prospective Study, a multicenter UK JIA inception cohort, were classified using the PRINTO and ILAR classification criteria into distinct categories. Systemic JIA was excluded because several classification items were not collected in this cohort. Adaptations to PRINTO criteria were required to apply to a UK health care setting, including limiting the number of blood biomarker tests required. The overlap between categories under the two systems was determined, and any differences in characteristics between groups were described. RESULTS: A total of 1,223 children and young people with a physician's diagnosis of JIA were included. Using PRINTO criteria, the majority of the patients had "other JIA" (69.5%). There was a high degree of overlap (91%) between the PRINTO enthesitis/spondylitis- and ILAR enthesitis-related JIA categories. The PRINTO rheumatoid factor (RF)-positive category was composed of 48% ILAR RF-positive polyarthritis and 52% undifferentiated JIA. The early-onset antinuclear antibodies-positive PRINTO category was largely composed of ILAR oligoarthritis (50%), RF-negative polyarthritis (24%), and undifferentiated JIA (23%). A few patients were unclassified under PRINTO (n = 3) and would previously have been classified as enthesitis-related JIA (n = 1) and undifferentiated JIA (n = 2) under ILAR. CONCLUSION: Under the preliminary PRINTO classification criteria for childhood arthritis, most children are not yet classified into a named category. These data can help support further delineation of the PRINTO criteria to ensure homogenous groups of children can be identified.

Adolescent and caregiver preferences for juvenile idiopathic arthritis treatment: a discrete-choice experiment.

BACKGROUND: This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA). METHODS: We conducted a discrete-choice experiment among adolescents with JIA in the United States (US) (n = 197) and United Kingdom (UK) (n = 100) and caregivers of children with JIA in the US (n = 207) and UK (n = 200). In a series of questions, respondents chose between experimentally designed profiles for hypothetical JIA treatments that varied in efficacy (symptom control; time until next flare-up), side effects (stomachache, nausea, and vomiting; headaches), mode and frequency of administration, and the need for combination therapy. Using a random-parameters logit model, we estimated preference weights for these attributes, from which we derived their conditional relative importance. RESULTS: On average, respondents preferred greater symptom control; greater time until the next flare-up; less stomachache, nausea, and vomiting; and fewer headaches. However, adolescents and caregivers in the US were generally indifferent across varying modes and frequencies of administration. UK adolescents and caregivers preferred tablets, syrup, or injections to intravenous infusions. US and UK adolescents were indifferent between treatment with monotherapy or combination therapy; caregivers in the UK preferred treatment with combination therapy to monotherapy. Subgroup analysis showed preference heterogeneity across characteristics including gender, treatment experience, and symptom experience in both adolescents and caregivers. CONCLUSIONS: Improved symptom control, prolonged time to next flare-up, and avoidance of adverse events such as headache, stomachache, nausea, and vomiting are desirable characteristics of treatment regimens for adolescents with JIA and their caregivers.

The impact of psoriasis on wellbeing and clinical outcomes in juvenile psoriatic arthritis.

OBJECTIVES: Juvenile psoriatic arthritis (JPsA) has varied clinical features that are distinctive to other juvenile idiopathic arthritis (JIA) categories. This study investigates whether such features impact patient-reported and clinical outcomes. METHODS: Children and young people (CYP) were selected if recruited to the Childhood Arthritis Prospective Study, a UK multicentre JIA inception cohort, between January 2001 and March 2018. At diagnosis, patient/parent-reported outcomes (as age-appropriate) included the parental global assessment (10 cm VAS), functional ability (CHAQ), pain (10 cm VAS), health-related quality of life (CHQ psychosocial score), mood/depressive symptoms (MFQ) and parent psychosocial health (GHQ). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA, PaGA respectively). Patient-reported outcomes and outcome trajectories were compared in i) CYP with JPsA versus other JIA categories, ii) CYP within JPsA, with and without psoriasis via multivariable linear regression. RESULTS: There were no significant differences in patient-reported outcomes at diagnosis between CYP with JPsA and non-JPsA. Within JPsA, those with psoriasis had more depressive symptoms (coefficient = 9.8, 95% CI = 0.5-19.0) than those without psoriasis at diagnosis. CYP with JPsA had 2.3 times the odds of persistent high PaGA than other ILAR categories, despite improving joint counts and PGA (95% CI 1.2, 4.6). CONCLUSION: CYP with psoriasis at JPsA diagnosis report worse mood, supporting a greater disease impact in those with both skin and joint involvement. Multidisciplinary care with added focus to support wellbeing in children with JPsA plus psoriasis may help improve these outcomes.

Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile-onset SLE.

OBJECTIVES: Juvenile-onset systemic lupus erythematosus (jSLE) affects 15-20% of lupus patients. Clinical heterogeneity between racial groups, age groups and individual patients suggests variable pathophysiology. This study aimed to identify highly penetrant damaging mutations in genes associated with SLE/SLE-like disease in a large national cohort (UK JSLE Cohort Study) and compare demographic, clinical and laboratory features in patient sub-cohorts with 'genetic' SLE vs remaining SLE patients. METHODS: Based on a sequencing panel designed in 2018, target enrichment and next-generation sequencing were performed in 348 patients to identify damaging gene variants. Findings were integrated with demographic, clinical and treatment related datasets. RESULTS: Damaging gene variants were identified in ∼3.5% of jSLE patients. When compared with the remaining cohort, 'genetic' SLE affected younger children and more Black African/Caribbean patients. 'Genetic' SLE patients exhibited less organ involvement and damage, and neuropsychiatric involvement developed over time. Less aggressive first line treatment was chosen in 'genetic' SLE patients, but more second and third line agents were used. 'Genetic' SLE associated with anti-dsDNA antibody positivity at diagnosis and reduced ANA, anti-LA and anti-Sm antibody positivity at last visit. CONCLUSION: Approximately 3.5% of jSLE patients present damaging gene variants associated with younger age at onset, and distinct clinical features. As less commonly observed after treatment induction, in 'genetic' SLE, autoantibody positivity may be the result of tissue damage and explain reduced immune complex-mediated renal and haematological involvement. Routine sequencing could allow for patient stratification, risk assessment and target-directed treatment, thereby increasing efficacy and reducing toxicity.

Quality improvement in juvenile idiopathic arthritis: a mixed-methods implementation pilot of the CAPTURE-JIA dataset.

BACKGROUND: A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following diagnosis. Refinements to clinical care pathways have the potential to improve clinical outcomes but a lack of consistent and contemporaneous clinical data presently precludes standard setting and implementation of meaningful quality improvement programmes. This study was the first to pilot clinical data collection and analysis using the CAPTURE-JIA dataset, and to explore patient and clinician-reported feasibility and acceptability data. METHODS: A multiphase mixed-methods approach enabled prospective collection of quantitative data to examine the feasibility and efficacy of dataset collection and of qualitative data informing the context and processes of implementation. An initial paper pilot informed the design of a bespoke electronic data collection system (the Agileware system), with a subsequent electronic pilot informing the final CAPTURE-JIA data collection tool. RESULTS: Paper collection of patient data was feasible but time-consuming in the clinical setting. Phase 1 paper pilot data (121 patients) identified three themes: problematic data items (14/62 data items received >40% missing data), formatting of data collection forms and a clinician-highlighted need for digital data collection, informing Phase 2 electronic data collection tool development. Patients and families were universally supportive of the collection and analysis of anonymised patient data to inform clinical care. No apparent preference for paper / electronic data collection was reported by families. Phase 3 electronic pilot data (38 patients) appeared complete and the system reported to be easy to use. Analysis of the study dataset and a dummy longitudinal dataset confirmed that all eleven JIA national audit questions can be answered using the electronic system. CONCLUSIONS: Multicentre CAPTURE-JIA data collection is feasible and acceptable, with a bespoke data collection system highlighted as the most satisfactory solution. The study is informing ongoing work towards a streamlined and flexible national paediatric data collection system to drive quality improvement in clinical care.

Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study.

OBJECTIVES: High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes. METHODS: Youth <18 years with pAAV, biopsy-confirmed pauci-immune glomerulonephritis and 12-month follow-up data were included from an international paediatric vasculitis registry. Presenting features and 12-month outcomes (eGFR, glucocorticoid-related adverse effects), were compared between patients receiving no, low-moderate (≤90mg/kg) and high (>90mg/kg) cumulative intravenous methylprednisolone (IVMP), and low (<0.5mg/kg/day prednisone equivalent), moderate (0.5-1.5mg/kg/day) and high (>1.5mg/kg/day) starting doses of oral glucocorticoids. RESULTS: Among 131 patients (101 granulomatosis with polyangiitis, 30 microscopic polyangiitis), 27 (21%) received no IVMP, 64 (49%) low-moderate and 29 (22%) high-dose IVMP, while 9 (7%) received low, 75 (57%) moderate and 47 (36%) high initial doses of oral glucocorticoids. Renal failure at diagnosis (p=0.022) and plasmapheresis use (p=0.0001) were associated with high-dose IVMP. Rates of glucocorticoid-related adverse effects ranged from 15-31% across dose levels, and glucocorticoid dosing did not associate with 12-month outcomes. CONCLUSIONS: Glucocorticoid dosing for pAAV-related renal disease was highly variable, and rates of adverse effects were high across all dosing groups. A significant proportion of patients received oral glucocorticoid or IVMP doses that were discordant with current adult guidelines. Higher glucocorticoid doses did not associate with improved outcomes.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: Data from the UK Juvenile-onset systemic lupus erythematosus cohort study.

INTRODUCTION: Juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune/inflammatory disease with significant morbidity and mortality. Neuropsychiatric (NP) involvement is a severe complication, encompassing a heterogeneous range of neurological and psychiatric manifestations. METHODS: Demographic, clinical, and laboratory features of NP-SLE were assessed in participants of the UK JSLE Cohort Study, and compared to patients in the same cohort without NP manifestations. RESULTS: A total of 428 JSLE patients were included in this study, 25% of which exhibited NP features, half of them at first visit. Most common neurological symptoms among NP-JSLE patients included headaches (78.5%), mood disorders (48.6%), cognitive impairment (42%), anxiety (23.3%), seizures (19.6%), movement disorders (17.7%), and cerebrovascular disease (14.9%). Peripheral nervous system involvement was recorded in 7% of NP-SLE patients. NP-JSLE patients more frequently exhibited thrombocytopenia (<100 × 109/L) (p = 0.04), higher C-reactive protein levels (p = 0.01), higher global pBILAG score at first visit (p < 0.001), and higher SLICC damage index score at first (p = 0.02) and last (p < 0.001) visit when compared to JSLE patients without NP involvement. CONCLUSIONS: A significant proportion of JSLE patients experience NP involvement (25%). Juvenile-onset NP-SLE most commonly affects the CNS and is associated with increased overall disease activity and damage.

Wearable Technologies for Children with Chronic Illnesses: An Exploratory Approach.

OBJECTIVE: To determine the utility of wearable technologies in physical activity assessment in three paediatric diseases, namely, Niemann-Pick C (NP-C), Juvenile Idiopathic Arthritis (JIA) and Duchenne Muscular Dystrophy (DMD). DESIGN: Exploratory study SETTING AND PATIENTS: Thirty children were recruited across three UK hospitals (Royal Manchester's Children Hospital, Great Ormond Street Children's Hospital, and the Great North Children's Hospital). Ten were diagnosed with NP-C, eight with DMD and twelve with JIA. INTERVENTION: All participants completed the 6-min walk test (6MWT) at enrolment. Patients were provided with disease-specific smartphone apps paired with a wearable device via Bluetooth. Ambulation was recorded in 30-min epochs measuring average daily maximum (ADM), average daily steps (ADS) and average daily steps per 30-min epoch (ASE). RESULTS: Median 6MWT results were 450 m, 325 m and 434.5 m for the NP-C, DMD and JIA cohorts, respectively. Wearable data capture was feasible in all three disease cohorts, although complete data capture was not sustained. A statistically significant between-cohort difference was identified for ADM, ADS and ASE. Statistically significant differences were found between DMD/JIA for ADM; NP-C/DMD for ADS and DMD/JIA for ASE. DISCUSSION: Wearable sensor technologies have the potential to provide additional information for our understanding of ambulation in chronic paediatric disease. The wearable devices were easy to use and popular with patients although key features need to be addressed to appropriately meet study objectives. As the technology continues to evolve at a rapid pace, opportunities to implement child friendly solutions are already available.

Clinical and laboratory phenotypes in juvenile-onset Systemic Lupus Erythematosus across ethnicities in the UK.

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms, disease progression and outcomes do not only vary between individuals and age groups, but also ethnicities. However, in children and young people, the influence of ethnicity on disease onset, phenotype and outcome has not been investigated in detail. In this study, we investigated clinical and laboratory characteristics in pediatric SLE patients from different ethnic backgrounds (White Caucasian, Asian, Black African/Caribbean) accessing data from a national cohort of jSLE patients (the UK JSLE Cohort Study). Among jSLE patients in the UK, ethnicity affects both the disease's clinical course and outcomes. At diagnosis, Black African/Caribbean jSLE patients show more "classical" laboratory and clinical features when compared to White Caucasian or Asian patients. Black African/Caribbean jSLE patients exhibit more renal involvement and more frequently receive cyclophosphamide and rituximab. Studies targeting ethnicity-specific contributors to disease expression and phenotypes are necessary to improve our pathophysiological understanding, diagnosis and treatment of jSLE.

Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma.

Background: Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. Methods: An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. Results: An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Conclusions: Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

Validation of novel patient-centred juvenile idiopathic arthritis-specific patient-reported outcome and experience measures (PROMs/PREMs).

BACKGROUND: Measuring the outcomes that matter to children and young people (CYP) with juvenile idiopathic arthritis (JIA), is a necessary precursor to patient-centred improvements in quality of clinical care. We present a two-centre validation of novel JIA patient-reported outcome and experience measures (PROM and PREM) developed as part of the CAPTURE-JIA project. METHODS: CYP with JIA were recruited from paediatric rheumatology clinics, completing the CAPTURE-JIA PROM and PREM, CHAQ and CHU 9D. A subset participated in face-to-face interviews and completed the PROM/PREM 1 week later. The OMERACT filter was applied and the three domains of validation assessed. Truth assessments included cognitive interviewing, sensitivity analysis and Spearman's correlations. Discrimination assessments included specificity and reliability testing. Feasibility was assessed using time to form completion and proportion of missing data. RESULTS: Eighty-two CYP and their families were recruited; ten cognitive interviews and fifteen PROM/PREM test/retests were conducted. Truth: CYP and parents understood the PROM/PREM and felt important areas were covered. PROM criteria had high sensitivities (> 70%) against similar items on the CHU 9D, with the exception of fatigue (58%). Correlations between similar PROM and CHU 9D criteria were moderate to very strong (coefficients 0.40-0.82.) Discrimination: high specificities (> 70%) on corresponding PROM and CHU 9D domains. Feasibility: median completion times for PROM 60 s (IQR 38-75) and PREM 49 s (IQR 30-60) respectively. CONCLUSION: The CAPTURE-JIA PROM and PREM are valid and feasible in UK paediatric rheumatology clinics. Embedding routine collection into clinical care would be a major step towards improving quality of care.

Different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis: the SIRJIA mixed-methods feasibility study.

BACKGROUND: In the UK, juvenile idiopathic arthritis is the most common inflammatory disorder in childhood, affecting 10 : 100,000 children and young people aged < 16 years each year, with a population prevalence of around 1 : 1000. Corticosteroids are commonly used to treat juvenile idiopathic arthritis; however, there is currently a lack of consensus as to which corticosteroid induction regimen should be used with various disease subtypes and severities of juvenile idiopathic arthritis. OBJECTIVE: The main study objective was to determine the feasibility of conducting a randomised controlled trial to compare the different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis. DESIGN: This was a mixed-methods study. Work packages included a literature review; qualitative interviews with children and young people with juvenile idiopathic arthritis and their families; a questionnaire survey and screening log to establish current UK practice; a consensus meeting with health-care professionals, children and young people with juvenile idiopathic arthritis, and their families to establish the primary outcome; a feasibility study to pilot data capture and to collect data for future sample size calculations; and a final consensus meeting to establish the final protocol. SETTING: The setting was rheumatology clinics across the UK. PARTICIPANTS: Children, young people and their families who attended clinics and health-care professionals took part in this mixed-methods study. INTERVENTIONS: This study observed methods of prescribing corticosteroids across the UK. MAIN OUTCOME MEASURES: The main study outcomes were the acceptability of a future trial for children, young people, their families and health-care professionals, and the feasibility of delivering such a trial. RESULTS: Qualitative interviews identified differences in the views of children, young people and their families on a randomised controlled trial and potential barriers to recruitment. A total of 297 participants were screened from 13 centres in just less than 6 months. In practice, all routes of corticosteroid administration were used, and in all subtypes of juvenile idiopathic arthritis. Intra-articular corticosteroid injection was the most common treatment. The questionnaire surveys showed the varying clinical practice across the UK, but established intra-articular corticosteroids as the treatment control for a future trial. The primary outcome of choice for children, young people, their families and health-care professionals was the Juvenile Arthritis Disease Activity Score, 71-joint count. However, results from the feasibility study showed that, owing to missing blood test data, the clinical Juvenile Arthritis Disease Activity Score should be used. The Juvenile Arthritis Disease Activity Score, 71-joint count, and the clinical Juvenile Arthritis Disease Activity Score are composite disease activity scoring systems for juvenile arthritis. Two final trial protocols were established for a future randomised controlled trial. LIMITATIONS: Fewer clinics were included in this feasibility study than originally planned, limiting the ability to draw strong conclusions about these units to take part in future research. CONCLUSIONS: A definitive randomised controlled trial is likely to be feasible based on the findings from this study; however, important recommendations should be taken into account when planning such a trial. FUTURE WORK: This mixed-methods study has laid down the foundations to develop the evidence base in this area and conducting a randomised control trial to compare different corticosteroid induction regimens in children and young people with juvenile idiopathic arthritis is likely to be feasible. STUDY REGISTRATION: Current Controlled Trials ISRCTN16649996. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 36. See the NIHR Journals Library website for further project information.

ABOUT JUVENILE IDIOPATHIC ARTHRITIS: Juvenile idiopathic arthritis refers to a group of conditions that cause inflammation and damage of the joints, starting in children and young people aged < 16 years. Treatments include anti-inflammatory medicines, disease-modifying/biologic medicines and corticosteroids. Young people often require corticosteroids at the start of their treatment, or in a flare with worsening inflammation, to get their juvenile idiopathic arthritis under control. A short course of corticosteroids can help and can be given by injection into the joint, through a drip into a vein, by injection into the muscle or in the form of tablets or liquid to be taken orally. Although they have been used for decades, there is no research to show the best way(s) of giving corticosteroids. STUDY AIMS: The study aimed to (1) agree on what corticosteroid treatments to compare in a treatment trial and the best way to measure changes in juvenile idiopathic arthritis to evaluate a quick-acting treatment and (2) find out if there are enough young people with active juvenile idiopathic arthritis in the UK to be included in such a study. METHODS: Published research on corticosteroids in juvenile idiopathic arthritis was reviewed. Health-care professionals were asked how they choose which corticosteroids to use and which method of administration to use. Interviews were carried out with children and young people and their families to (1) consider the design of a study comparing corticosteroid routes, (2) identify outcomes important to them and (3) determine whether or not they would be willing to take part in a future study. A 3-month feasibility study was carried out to collect details of children and young people with active juvenile idiopathic arthritis before and after corticosteroid treatment to measure improvements in juvenile idiopathic arthritis activity, and to see whether or not a larger study would be possible. FINDINGS: This study showed that corticosteroids are used in different ways across the UK. The views of children, young people and their families must be taken into account when designing a future study. This study calculated the number of young people who would be needed to take part in the future, showing that it would be possible to do a larger study that compared different corticosteroid treatments, which would help everyone to understand the best way to use corticosteroids.

CAPTURE-JIA: a consensus-derived core dataset to improve clinical care for children and young people with juvenile idiopathic arthritis.

OBJECTIVES: Data collected during routine clinic visits are key to driving successful quality improvement in clinical services and enabling integration of research into routine care. The purpose of this study was to develop a standardized core dataset for juvenile idiopathic arthritis (JIA) (termed CAPTURE-JIA), enabling routine clinical collection of research-quality patient data useful to all relevant stakeholder groups (clinicians, service-providers, researchers, health service planners and patients/families) and including outcomes of relevance to patients/families. METHODS: Collaborative consensus-based approaches (including Delphi and World Café methodologies) were employed. The study was divided into discrete phases, including collaborative working with other groups developing relevant core datasets and a two-stage Delphi process, with the aim of rationalizing the initially long data item list to a clinically feasible size. RESULTS: The initial stage of the process identified collection of 297 discrete data items by one or more of fifteen NHS paediatric rheumatology centres. Following the two-stage Delphi process, culminating in a consensus workshop (May 2015), the final approved CAPTURE-JIA dataset consists of 62 discrete and defined clinical data items including novel JIA-specific patient-reported outcome and experience measures. CONCLUSIONS: CAPTURE-JIA is the first 'JIA core dataset' to include data items considered essential by key stakeholder groups engaged with leading and improving the clinical care of children and young people with JIA. Collecting essential patient information in a standard way is a major step towards improving the quality and consistency of clinical services, facilitating collaborative and effective working, benchmarking clinical services against quality indicators and aligning treatment strategies and clinical research opportunities.

Comparing Proxy, Adolescent, and Adult Assessments of Functional Ability in Adolescents With Juvenile Idiopathic Arthritis.

OBJECTIVE: In pediatric research, investigators rely on proxy reports of outcome, such as the proxy-completed Childhood Health Assessment Questionnaire (C-HAQ), to assess function in juvenile idiopathic arthritis (JIA). As children mature, they may self-complete the adult HAQ or the unvalidated adolescent-specific C-HAQ. It is unclear how these measures compare and whether they are directly interchangeable. The present study was undertaken to compare agreement between the proxy-completed C-HAQ, adolescent-specific C-HAQ, and the HAQ at initial presentation to pediatric rheumatologic care and 1 year following the first presentation in adolescents with JIA. METHODS: Adolescents ages 11-17 years participating in the Childhood Arthritis Prospective Study (CAPS), a UK multicenter inception cohort, were included. In a CAPS substudy, adolescents self-completed the adolescent-specific C-HAQ and the HAQ, and proxies simultaneously completed the proxy-completed C-HAQ at baseline and 1 year. Correlation and agreement between scores were assessed at baseline. Agreement and ability to similarly classify clinically important changes over time were assessed at 1 year following initial presentation to rheumatologic care. RESULTS: A total of 107 adolescents (adolescent-specific C-HAQ and HAQ) or their proxies (proxy-completed C-HAQ) had completed all 3 measures at baseline. Median age at diagnosis was 13 years, and 61% were female. Although the 3 scores demonstrated strong correlations (r > 0.8), they were not completely interchangeable, with agreement ranging between 70% and 80%. There was similar agreement between the changes in scores between baseline and 1 year. Using proxy-completed C-HAQ minimum clinically important cutoffs, the adolescent-specific C-HAQ and the HAQ similarly classified 80% to 90% of adolescents as having improved or worsened. CONCLUSION: While there is relatively high agreement and similar classification of change between HAQ and the 2 C-HAQ scores, these are not completely interchangeable. This impacts the comparison of function when measured in different ways over the lifespan.

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

BACKGROUND: Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria. The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families. METHODS: Children and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children's Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count. RESULTS: Eleven young people (5 male, median age 13 years, range 7-16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm3 (82.1cm3) to 0.0cm3 (0.2cm3). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients. CONCLUSIONS: IAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.

Multi-centre national audit of juvenile localised scleroderma: describing current UK practice in disease assessment and management.

OBJECTIVE: To describe current United Kingdom practice in assessment and management of patients with juvenile localised scleroderma (JLS) compared to Paediatric Rheumatology European Society (PRES) scleroderma working party recommendations. METHODS: Patients were included if they were diagnosed with JLS and were under the care of paediatric rheumatology between 04/2015-04/2016. Retrospective data was collected in eleven UK centres using a standardised proforma and collated centrally. RESULTS: 149 patients were included with a median age of 12.5 years. The outcome measures recommended by the PRES scleroderma working party were not utilised widely. The localised scleroderma cutaneous assessment tool was only used in 37.6% of patients. Screening for extracutaneous manifestations did not meet recommendations that patients with head involvement have regular screening for uveitis and baseline magnetic resonance imaging (MRI) brain: only 38.5% of these patients were ever screened for uveitis; 71.2% had a MRI brain. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) or biologics was widely used (96.0%). In keeping with the recommendations, 95.5% of patients were treated with methotrexate as first-line therapy. 82.6% received systemic corticosteroids and 34.2% of patients required two or more DMARDs/biologics, highlighting the significant treatment burden. Second-line treatment was mycophenolate mofetil in 89.5%. CONCLUSION: There is wide variation in assessment and screening of patients with JLS but a consistent approach to systemic treatment within UK paediatric rheumatology. Improved awareness of PRES recommendations is required to ensure standardised care. As recommendations are based on low level evidence and consensus opinion, further studies are needed to better define outcome measures and treatment regimens for JLS.

Protective parents and permissive children: what qualitative interviews with parents and children can tell us about the feasibility of juvenile idiopathic arthritis trials.

BACKGROUND: Patient recruitment can be very challenging in paediatric studies, especially in relatively uncommon conditions, such as juvenile idiopathic arthritis (JIA). However, involving children and young people (CYP) in the design of such trials could promise a more rapid trajectory towards making evidence-based treatments available. Studies involving CYP are advocated in the literature but we are not aware of any early stage feasibility studies that have qualitatively accessed the perspectives of parents and CYP with a long term condition to inform design and conduct of a trial. In the context of a feasibility study to inform the design of a proposed randomised controlled trial of corticosteroid induction regimen in JIA, we explored families' perspectives on the proposed trial and on JIA trials generally. METHODS: We analysed interviews with 27 participants (8 CYP aged 8-16 years and 19 parents) from four UK paediatric rheumatology centres. CYP had recently received corticosteroids to treat JIA. Audio-recorded interviews were transcribed and analysed thematically, drawing on the Framework Method. RESULTS: Both parents and CYP were capable of engaging with the logic of the proposed trial but pointed to challenges with its design. Treatment preferences influenced willingness to participate in the proposed trial. The preferences of older children and their parents often differed, with CYP being more willing to participate in the proposed trial than parents. Families' current treatment preferences were largely informed by past positive and negative treatment experiences. Some participants also indicated that their treatment preferences were influenced by those of their clinicians. CONCLUSION: Previous research has typically focused on deficits in patients' understandings of trials. We found that both parents and CYP understood trial concepts and were able to identify potential flaws in the proposed trial. We propose recommendations to optimise the design of a planned corticosteroid induction regimen trial in JIA. Accessing both parents' and CYP's perspectives helps to identify and address recruitment challenges, which will ultimately optimise informed consent and future recruitment.

Long-Term Outcomes Following Achievement of Clinically Inactive Disease in Juvenile Idiopathic Arthritis: The Importance of Definition.

OBJECTIVE: Potential targets for treat-to-target strategies in juvenile idiopathic arthritis are minimal disease activity (MDA) and clinically inactive disease (CID). We undertook this study to compare short- and long-term outcomes following achievement of MDA and CID on the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10) and following achievement of CID on Wallace et al's preliminary criteria. METHODS: Children recruited to the Childhood Arthritis Prospective Study, a UK multicenter inception cohort, were selected if they were recruited prior to January 2011 and diagnosed as having oligoarthritis or rheumatoid factor-negative or -positive polyarthritis. One year following diagnosis, children were assessed for MDA on the cJADAS10 and for CID on both Wallace et al's preliminary criteria and the cJADAS10. Associations were tested between those disease states and functional ability, absence of joints with limited range of motion, psychosocial health, and pain at 1 year and annually to 5 years. RESULTS: Of 832 children, 70% were female and the majority had oligoarthritis (68%). At 1 year, 21% had achieved CID according to both definitions, 7% according to Wallace et al's preliminary criteria alone, and 16% according to the cJADAS10 alone; 56% had not achieved CID. Only 10% of children in the entire cohort achieved MDA without also achieving CID. Achieving either early CID state was associated with a greater absence of joints with limited range of motion. However, only CID according to the cJADAS10 was associated with improved functional ability and psychosocial health. Achieving CID was superior to achieving MDA in terms of short- and long-term pain and the absence of joints with limited range of motion. CONCLUSION: CID on the cJADAS10 may be preferable as a treatment target to CID on Wallace et al's preliminary criteria in terms of both feasibility of application and long-term outcomes.

Prevalence and course of lower limb disease activity and walking disability over the first 5 years of juvenile idiopathic arthritis: results from the childhood arthritis prospective study.

OBJECTIVE: The aim was to investigate the time course of lower limb disease activity and walking disability in children with JIA over a 5-year course. METHODS: The Childhood Arthritis Prospective Study is a longitudinal study of children with a new JIA diagnosis. Childhood Arthritis Prospective Study data include demographics and core outcome variables at baseline, 6 months and yearly thereafter. Prevalence and transition rates from baseline to 5 years were obtained for active and limited joint counts at the hip, knee, ankle and foot joints; and walking disability, measured using the Childhood Health Assessment Questionnaire walking subscale. Missing data were accounted for using multiple imputation. RESULTS: A total of 1041 children (64% female), with a median age of 7.7 years at first visit, were included. Baseline knee and ankle synovitis prevalence was 71 and 34%, respectively, decreasing to 8-20 and 6-12%, respectively, after 1 year. Baseline hip and foot synovitis prevalence was <11%, decreasing to <5% after 6 months. At least mild walking disability was present in 52% at baseline, stabilizing at 25-30% after 1 year. CONCLUSION: Lower limb synovitis and walking disability are relatively common around the time of initial presentation in children and young people with JIA. Mild to moderate walking disability persisted in ∼25% of patients for the duration of the study, despite a significant reduction in the frequency of lower limb synovitis. This suggests that there is an unmet need for non-medical strategies designed to prevent and/or resolve persistent walking disability in JIA.