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.

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.

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.

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.

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.

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership.

Objective: Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. Methods: A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Results: Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. Conclusion: A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services.

How common is clinically inactive disease in a prospective cohort of patients with juvenile idiopathic arthritis? The importance of definition.

OBJECTIVES: Many criteria for clinically inactive disease (CID) and minimal disease activity (MDA) have been proposed for juvenile idiopathic arthritis (JIA). It is not known to what degree each of these criteria overlap within a single patient cohort. This study aimed to compare the frequency of MDA and CID across different criteria in a cohort of children with JIA at 1 year following presentation. METHODS: The Childhood Arthritis Prospective Study recruits children at initial presentation to paediatric or adolescent rheumatology in seven UK centres. Children recruited between October 2001 and December 2013 were included. The proportions of children with CID and MDA at 1 year were calculated using four investigator-defined and eight published composite criteria. Missing data were accounted for using multiple imputation under different assumptions. RESULTS: In a cohort of 1415 children and adolescents, 67% patients had no active joints at 1 year. Between 48% and 61% achieved MDA and between 25% and 38% achieved CID using published criteria. Overlap between criteria varied. Of 922 patients in MDA by either the original composite criteria, Juvenile Arthritis Disease Activity Score (JADAS) or clinical JADAS cut-offs, 68% were classified as in MDA by all 3 criteria. Similarly, 44% of 633 children with CID defined by either Wallace's preliminary criteria or the JADAS cut-off were in CID according to both criteria. CONCLUSIONS: In a large JIA prospective inception cohort, a majority of patients have evidence of persistent disease activity after 1 year. Published criteria to capture MDA and CID do not always identify the same groups of patients. This has significant implications when defining and applying treat-to-target strategies.

Trends in paediatric rheumatology referral times and disease activity indices over a ten-year period among children and young people with Juvenile Idiopathic Arthritis: results from the childhood arthritis prospective Study.

OBJECTIVES: The medical management of JIA has advanced significantly over the past 10 years. It is not known whether these changes have impacted on outcomes. The aim of this analysis was to identify and describe trends in referral times, treatment times and 1-year outcomes over a 10-year period among children with JIA enrolled in the Childhood Arthritis Prospective Study. METHODS: The Childhood Arthritis Prospective Study is a prospective inception cohort of children with new-onset inflammatory arthritis. Analysis included all children recruited in 2001-11 with at least 1 year of follow-up, divided into four groups by year of diagnosis. Median referral time, baseline disease pattern (oligoarticular, polyarticular or systemic onset) and time to first definitive treatment were compared between groups. Where possible, clinical juvenile arthritis disease activity score (cJADAS) cut-offs were applied at 1 year. RESULTS: One thousand and sixty-six children were included in the analysis. The median time from symptom onset and referral to first paediatric rheumatology appointment (22.7-24.7 and 3.4-4.7 weeks, respectively) did not vary significantly (∼20% seen within 10 weeks of onset and ∼50% within 4 weeks of referral). For oligoarticular and polyarticular disease, 33.8-47 and 25.4-34.9%, respectively, achieved inactive disease by 1 year, with ∼30% in high disease activity at 1 year. A positive trend towards earlier definitive treatment reached significance in oligoarticular and polyarticular pattern disease. CONCLUSION: Children with new-onset JIA have a persistent delay in access to paediatric rheumatology care, with one-third in high disease activity at 1 year and no significant improvement over the past 10 years. Contributing factors may include service pressures and poor awareness. Further research is necessary to gain a better understanding and improve important clinical outcomes.

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.

Validity of a three-variable Juvenile Arthritis Disease Activity Score in children with new-onset juvenile idiopathic arthritis.

OBJECTIVES: To investigate the validity and feasibility of the Juvenile Arthritis Disease Activity Score (JADAS) in the routine clinical setting for all juvenile idiopathic arthritis (JIA) disease categories and explore whether exclusion of the erythrocyte sedimentation rate (ESR) from JADAS (the 'JADAS3') influences correlation with single markers of disease activity. METHODS: JADAS-71, JADAS-27 and JADAS-10 were determined at baseline for an inception cohort of children with JIA in the Childhood Arthritis Prospective Study. JADAS3-71, JADAS3-27 and JADAS3-10 were determined using an identical formula but with exclusion of ESR. Correlation of JADAS with JADAS3 and single measures of disease activity/severity were determined by category. RESULTS: Of 956 eligible children, sufficient data were available to calculate JADAS-71, JADAS-27 and JADAS-10 at baseline in 352 (37%) and JADAS3 in 551 (58%). The median (IQR) JADAS-71, JADAS-27 and JADAS-10 for all 352 children was 11 (5.9-18), 10.4 (5.7-17) and 11 (5.9-17.3), respectively. Median JADAS and JADAS3 varied significantly with the category (Kruskal-Wallis p=0.0001), with the highest values in children with polyarticular disease patterns. Correlation of JADAS and JADAS3 across all categories was excellent. Correlation of JADAS71 with single markers of disease activity/severity was good to moderate, with some variation across the categories. With the exception of ESR, correlation of JADAS3-71 was similar to correlation of JADAS-71 with the same indices. CONCLUSIONS: This study is the first to apply JADAS to all categories of JIA in a routine clinical setting in the UK, adding further information about the feasibility and construct validity of JADAS. For the majority of categories, clinical applicability would be improved by exclusion of the ESR.

Recent developments in disease activity indices and outcome measures for juvenile idiopathic arthritis.

There has been a concerted and important international effort to develop and validate disease activity and outcome instruments specific to JIA in recent years. This review aims to describe the disease assessment indices important to routine clinical care and integral to the design of outcome studies and clinical trials in JIA. In view of the increasing number of JIA clinical studies and clinical trials, together with a number of national and international paediatric biologic registers, it is important that knowledge of these new outcome measures is widespread, such that results can be placed in a meaningful context.

Biologic treatment response among adults with juvenile idiopathic arthritis: results from the British Society for Rheumatology Biologics Register.

OBJECTIVE: To describe the use of and response to biologic therapies commenced in adults with JIA. METHODS: Patients with arthritis onset <16 years were identified from the British Society for Rheumatology Biologics Register for rheumatoid arthritis (BSRBR-RA) and stratified into ILAR JIA subtypes. Patterns of biologic use and treatment persistence were explored, with disability levels (HAQ) and remission rates [28-Joint Disease Activity Score (DAS28)] evaluated at 6 and 12 months. RESULTS: Arthritis with an onset of <16 years was confirmed in 225 patients and the ILAR subtype was determined in 154 (68%). Only 58 (26%) patients had a diagnosis of JIA recorded in the BSRBR-RA. The median age at biologic commencement was 31 years [interquartile range (IQR) 23-39] and 76% were female. The biologic therapies were etanercept (49%), infliximab (28%), adalimumab (22%) and anakinra (1%). Fifty per cent of patients received more than one biologic during follow-up (2 agents, n = 64; ≥3 agents, n = 49). Treatment persistence at 1 year was 78% (95% CI 71%, 82%), falling to 42% (95% CI 34%, 49%) at 5 years. Both the HAQ and DAS28 improved significantly at 6 months, with 21% and 28% of patients in remission (DAS28 < 2.6) at 6 and 12 months, respectively. CONCLUSION: This study describes patterns and identifies outcomes of biologic use in a national cohort of adults with JIA. With no national guidance currently available in this area, the choice of first biologic was inconsistent, although treatment outcomes were good. These data confirm that biologic therapies are an important treatment option in adults with active JIA in adulthood.

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.

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.

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.

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.

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.