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Objectives Juvenile PsA (JPsA) has varied clinical features that are distinctive from other 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 visual analogue scale), functional ability (Childhood Health Assessment Questionnaire (CHAQ)), pain (10 cm visual analogue scale), health-related quality of life (Child Health Questionnaire PF50 psychosocial score), mood/depressive symptoms (Moods and Feelings Questionnaire) and parent psychosocial health (General Health Questionnaire 30). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA and PaGA, respectively). Patient-reported outcomes and outcome trajectories were compared in (i) CYP with JPsA vs other JIA categories and (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenileonset 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 toWhite 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives To investigate early vertical growth patterns and factors associated with poor growth in a modern inception cohort of UK children with juvenile idiopathic arthritis (JIA) using data from the Childhood Arthritis Prospective Study (CAPS). Methods A study period of 3 years was chosen. Children included in this analysis had a physician diagnosis of JIA and had height measurements available at both baseline and at 3-years of follow-up. Height is presented as z -scores calculated using World Health Organisation growth standards for age and gender. Growth over the 3-year period was assessed using change in z -score and height velocity. Univariable and multivariable linear regressions were used to identify factors associated with height z -score at baseline and change of height z -score at 3 years. Results 568 patients were included; 65% female, median baseline age 7.4 years [interquartile range (IQR) 3.6, 11.2], median symptom duration at presentation 5.5 months [IQR 3.1, 11.6]. Height z -score decreased significantly from baseline to 3 years ( p ≤ 0.0001); baseline median height z -score was −0.02 (IQR −0.71, 0.61), decreasing to −0.47 (IQR −1.12, 0.24) at 3 years. Growth restriction, defined as change of height z -score ≤−0.5, was observed in 39% of patients. At 3 years, higher baseline height z -score was the strongest predictor for a negative change in height z -score [−0.3 per unit of baseline height z -score (95% CI: −0.36, −0.24), p < 0.0001]. Conclusions Although overall height at 3 years after initial presentation to rheumatology is within the population norm, as a cohort, children with JIA experience a reduction of growth in height over the first 3 years of disease. Late presentation to paediatric rheumatology services is associated with lower height at presentation. However, patients with the lowest height z scores at presentation were also the most likely to see an improvement at 3 years. The impact of JIA on growth patterns is important to children and families and this study provides useful new data to support informed clinical care. [ABSTRACT FROM AUTHOR]

Objectives: Pain is a very common symptom of juvenile idiopathic arthritis (JIA). Disease activity alone cannot explain symptoms of pain in all children, suggesting other factors may be relevant. The objectives of this study were to describe the different patterns of pain experienced over time in children with JIA and to identify predictors of which children are likely to experience ongoing pain.Methods: This study used longitudinal-data from patients (aged 1-16 years) with new-onset JIA. Baseline and up to 5-year follow-up pain data from the Childhood Arthritis Prospective Study (CAPS) were used. A two-step approach was adopted. First, pain trajectories were modelled using a discrete mixture model. Second, multinomial logistic regression was used to determine the association between variables and trajectories.Results: Data from 851 individuals were included (4 years, median follow-up). A three-group trajectory model was identified: consistently low pain (n=453), improved pain (n=254) and consistently high pain (n=144). Children with improved pain or consistently high pain differed on average at baseline from consistently low pain. Older age at onset, poor function/disability and longer disease duration at baseline were associated with consistently high pain compared with consistently low pain. Early increases in pain and poor function/disability were also associated with consistently high pain compared with consistently low pain.Conclusions: This study has identified routinely collected clinical factors, which may indicate those individuals with JIA at risk of poor pain outcomes earlier in disease. Identifying those at highest risk of poor pain outcomes at disease onset may enable targeted pain management strategies to be implemented early in disease thus reducing the risk of poor pain outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background There is a challenging lack of evidence to inform best practice in the routine clinical care of juvenile idiopathic arthritis (JIA). Wide inter-centre variation in the definition and documentation of clinical data items is a major barrier to improvement. In response, we have developed a consensus agreed standardised core dataset called CAPTURE-JIA (n = 62 data items and a 'data dictionary' including agreed definitions of terms) designed to support routine collection of high-quality clinical data. The feasibility and acceptability of CAPTURE-JIA in clinical practice is not yet known and was the focus of this pilot study. Methods A purposeful sample of six paediatric rheumatology centres across England was invited to collect the CAPTURE-JIA dataset using paper collection forms (n = 20 patients/centre). The dataset was analysed for missing data. Six focus groups (n = 3-10) explored clinicians' views on acceptability and feasibility. Results One hundred and twenty-one patients were recruited over three months. The completeness of the dataset was similar across centres, with minor variations. The majority of data items (eg demographics, dates, ILAR type and examination) were >80% completed. However, 14/62 data items received >40% missing data. (Table 1) Further descriptive analyses highlighted incorrect completion of paper forms. Three themes emerged from the focus groups: problematic data items (missing from >10% forms at > 1 centre), format of clinician data forms and the role of digital data collection. Suggested solutions included minor changes to data item definitions and formatting. There were no refinements to the data items. Development of a digital data collection system was identified by all as essential. Due to a lack of clear consensus, the original CAPTURE forms included a number of ways to record joint count data. This proved confusing and a unanimous decision was taken to collect joint count data on all 83 joints in a tabular format. P10 Table 1: CAPTURE JIA data items with >40% missing data Data item  % forms with data item missing (if item required)  Relevant co-morbidities?  60  Macrophage activation syndrome?  100  Has the ILAR subtype changed?  50  Morning stiffness lasting >15 minutes?  42  History of any form of uveitis?  52  Date started uveitis mediation?  50  Strength of uveitis medication?  83  Counselled prior to new DMARD / biologic?  56  Enrolled in BECS/BCRD if new DMARD / biologic?  48  Joint count (homunculus or table format)  48  Physician assessment of systemic disease activity (VAS)  75  ESR  74  CRP  92  Plasma viscosity  100  Data item  % forms with data item missing (if item required)  Relevant co-morbidities?  60  Macrophage activation syndrome?  100  Has the ILAR subtype changed?  50  Morning stiffness lasting >15 minutes?  42  History of any form of uveitis?  52  Date started uveitis mediation?  50  Strength of uveitis medication?  83  Counselled prior to new DMARD / biologic?  56  Enrolled in BECS/BCRD if new DMARD / biologic?  48  Joint count (homunculus or table format)  48  Physician assessment of systemic disease activity (VAS)  75  ESR  74  CRP  92  Plasma viscosity  100  P10 Table 1: CAPTURE JIA data items with >40% missing data Data item  % forms with data item missing (if item required)  Relevant co-morbidities?  60  Macrophage activation syndrome?  100  Has the ILAR subtype changed?  50  Morning stiffness lasting >15 minutes?  42  History of any form of uveitis?  52  Date started uveitis mediation?  50  Strength of uveitis medication?  83  Counselled prior to new DMARD / biologic?  56  Enrolled in BECS/BCRD if new DMARD / biologic?  48  Joint count (homunculus or table format)  48  Physician assessment of systemic disease activity (VAS)  75  ESR  74  CRP  92  Plasma viscosity  100  Data item  % forms with data item missing (if item required)  Relevant co-morbidities?  60  Macrophage activation syndrome?  100  Has the ILAR subtype changed?  50  Morning stiffness lasting >15 minutes?  42  History of any form of uveitis?  52  Date started uveitis mediation?  50  Strength of uveitis medication?  83  Counselled prior to new DMARD / biologic?  56  Enrolled in BECS/BCRD if new DMARD / biologic?  48  Joint count (homunculus or table format)  48  Physician assessment of systemic disease activity (VAS)  75  ESR  74  CRP  92  Plasma viscosity  100  Conclusion Paper collection of the CAPTURE-JIA data items is feasible and acceptable in the routine clinical setting, but unlikely to be sustainable in the longer term if collected in duplicate with medical notes. A digital tool in the clinical domain, ideally interlocking with local systems, would offer many advantages, including more complete and time-efficient data collection. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Juvenile idiopathic arthritis (JIA) is an umbrella term for seven relapsing-remitting inflammatory conditions in children and young people (CYP). Early, intensive treatment can prevent long-term damage; however, established drugs exhibit a delayed response, prompting the need for rapid-onset treatment in the form of corticosteroids. Given a lack of consensus as to which corticosteroid induction regimen should be used for CYP with JIA, a feasibility trial of different regimens is needed. The aim was to achieve consensus among CYP, families, and healthcare professionals (HCPs) about the primary outcome measures and protocol components to include in a prospective feasibility study. Methods A modified Nominal Group Technique was used to achieve consensus on the most appropriate primary outcome measure to be included in a prospective feasibility study, in addition to other protocol components such as inclusion/exclusion criteria. Fifteen participants participated in the process, including a combination of CYP with JIA, families (n = 9) and HCPs (n = 6). Results In the first vote, participants agreed that Juvenile Arthritis Disease Activity Score (JADAS) and Physician Global Assessment Score were most meaningful. During sub-group discussions, the need for a composite score which captured the voice of CYP and families was emphasised. In the second vote, JADAS and the JIA Core Set were identified as the most important. Further discussions led to the results of the third vote, agreeing JADAS as the primary outcome measure of choice being measured at 6 weeks after commencement of treatment. The majority of HCPs, CYP and families voted for all JIA sub-types to be included in a prospective feasibility study, with some queries about the inclusion of systemic JIA given its unique presentation. Participants also identified the need for more frequent data collection time points to capture the rapid onset of corticosteroid action, while CYP and families opted for accessible mechanisms for participation, such as digital follow-up strategies. Conclusion It is feasible to include CYP, families and HCPs in synthesising complex concepts to agree by consensus the design components of clinical research. The primary outcome measure for inclusion in a prospective feasibility study of corticosteroid regimens in CYP with JIA was co-prioritised, with CYP and families taking a leading role in the ultimate selection of an appropriate outcome measure and other study protocol components. Using consensus methods with CYP, families and HCPs is a systematic and rigorous way in which to select outcome measures that are both meaningful and relevant to everyone involved in the care and treatment of CYP with JIA. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Background Corticosteroids (CS) are widely used for rapid-action or induction treatment in children and young people (CYP) with juvenile idiopathic arthritis (JIA). Given a lack of evidence base on CS induction regimen for CYP with JIA, and since criteria for choosing CS are based on healthcare professional (HCP) preference, further research is needed (1). Methods A national electronic survey was undertaken among HCPs across the UK as part of the Steroid Induction Regimen for Juvenile Idiopathic Arthritis (SIRJIA) study. We aimed to establish the opinions of HCPs current practice regarding the clinical criteria for commencing CS treatment Results A total of 39 (24%) responses were received from 162 HCPs. These included 22 (56%) NHS consultants, five (13%) grid trainees, eight (21%) clinical nurse specialists and four other HCPs (10%). The most common treatments newly diagnosed JIA or a disease flare were intra-articular IACS or a combination of DMARDs and IAS (except for systemic JIA and oligoarticular JIA). The majority of HCPs 17 would treat new and flaring CYP the same with 53% choosing a different regime or not answering. The key criteria HCPs used for commencing CS and choosing route of administration were rapid induction of remission (31 (89%)), high disease activity (31 (89%)), severity of systemic JIA (30 (86%)) and level of inflammation (28 (80%)), see Table 1. The main determinants of route of administration was disease severity disease subtype. The majority of HCPs (52-72%) would consider entering CYP with JIA into a trial randomising to modes of administration. P14 Table 1 Reasons of CS Choice  Number N = 39  Percentage %  High Disease Activity  35  89.7  Rapid induction of remission  34  87.18  Severity of Systemic JIA  34  87.18  Level of inflammation  32  82.5  Severe Uveitis  30  76.92  JIA subtype  27  68.21  Targeting Specific Joints  26  66.67  Level of Disability  18  46.15  Level of pain  16  41.03  Long-standing Disease  11  28.1  Patient reluctance to take DMARDS  8  20.5  Reasons of CS Choice  Number N = 39  Percentage %  High Disease Activity  35  89.7  Rapid induction of remission  34  87.18  Severity of Systemic JIA  34  87.18  Level of inflammation  32  82.5  Severe Uveitis  30  76.92  JIA subtype  27  68.21  Targeting Specific Joints  26  66.67  Level of Disability  18  46.15  Level of pain  16  41.03  Long-standing Disease  11  28.1  Patient reluctance to take DMARDS  8  20.5  P14 Table 1 Reasons of CS Choice  Number N = 39  Percentage %  High Disease Activity  35  89.7  Rapid induction of remission  34  87.18  Severity of Systemic JIA  34  87.18  Level of inflammation  32  82.5  Severe Uveitis  30  76.92  JIA subtype  27  68.21  Targeting Specific Joints  26  66.67  Level of Disability  18  46.15  Level of pain  16  41.03  Long-standing Disease  11  28.1  Patient reluctance to take DMARDS  8  20.5  Reasons of CS Choice  Number N = 39  Percentage %  High Disease Activity  35  89.7  Rapid induction of remission  34  87.18  Severity of Systemic JIA  34  87.18  Level of inflammation  32  82.5  Severe Uveitis  30  76.92  JIA subtype  27  68.21  Targeting Specific Joints  26  66.67  Level of Disability  18  46.15  Level of pain  16  41.03  Long-standing Disease  11  28.1  Patient reluctance to take DMARDS  8  20.5  Conclusion The results from this national survey of clinical practice showed varying practices in the management of new CYP with JIA and those that are flaring. The majority of HCPs who completed this survey, indicated that they would be prepared to consider entering CYP into a trial that randomised to the four CS delivery methods. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Poster presentation Tuesday 8 October Background The ankle is one of the most commonly affected joints in juvenile idiopathic arthritis (JIA) and ankle joint damage is a known complication. The frequency of ankle damage in modern JIA cohorts is unknown and optimal management pathways are unclear. Magnetic resonance imaging (MRI) is the most sensitive imaging modality for the assessment of joint damage. The aim of this analysis was to investigate the demographics, disease features and management of JIA patients with MRI changes consistent with ankle damage. Methods A single-centre, retrospective study over a four year period was conducted. JIA cases with damage based on MRI features were included in the study. MRI was reviewed by an experienced musculoskeletal radiologist and joint damage was defined as radiological evidence of cartilage loss or joint space narrowing. A standardised electronic pro forma was used to record demographics, disease features and treatments received. Results Fifty one JIA cases had an MRI scan during the study period and 16/51 (31%) had radiological evidence of ankle damage at a median interquartile range (IQR) follow-up of 7.6 (6.9 – 11.0) years; 7/16 (44%) had developed bilateral ankle damage. The median (IQR) duration of symptoms at diagnosis was 2(1.0-10.5) months. The mean age at diagnosis and at detection of ankle damage was 5.2 years and 12.1 years respectively. The most frequent JIA subtype was oligo-articular extended (50%), and 50% were ANA positive. The median (IQR) duration between detection of ankle damage and first episode of ankle synovitis was 5.4 (4.6 – 6.4) years. Ankle synovitis was present at diagnosis in 10/16 (62%). Median (IQR) number of ankle corticosteroid injections before the ankle damage was detected was 3 (2-3), one patient had evidence of damage at diagnosis. Median (IQR) number of any type of ankle imaging done before the ankle damage was detected was 1 (1-3). The median (IQR) time to start methotrexate from diagnosis was 6 (0 - 29.5) months and median (IQR) number of biologic and synthetic DMARDs used at follow-up were 3.5 (2.2 – 4.0). 7/16 (44%) patients had undergone an orthopaedic surgical procedure for their ankle damage. Conclusion Ankle synovitis at presentation and an extended oligo-articular disease course were common in this cohort of children and young people (CYP) with JIA and ankle damage. Ankle damage is an important challenge in JIA; a substantial number of this cohort ultimately required surgical intervention. There is an urgent need to develop a care pathway designed to improve early recognition and management of evolving ankle joint damage in JIA. Our analysis suggests that attention may need to focus on CYP presenting with ankle synovitis, particularly those who develop a poly-articular disease course, may merit high levels of vigilance with be at particularly high risk. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis.Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman’s rank statistic.Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers.Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR.Disclosure statement: All authors have declared no conflicts of interest.Table 1Spearman’s correlation between JADAS 71 and single markers DA by ILAR subtypeILAR SubtypeSystemic onset JIAPersistent oligo JIAExtended oligo JIARheumatoid factor neg JIARheumatoid factor pos JIAEnthesitis related JIAPsoriatic JIAUndifferentiated JIAUnknown subtypeTotal cohortNumber of children2311112577919717262AJC0.540.670.530.750.530.340.590.810.370.59PGA0.630.690.250.730.140.050.500.830.560.64PGE0.510.680.830.610.410.690.710.90.480.61ESR0.280.310.350.40.60.850.430.70.50.53Limited 71 JC0.290.510.230.370.14-0.120.40.810.450.41Parental pain0.230.620.030.570.410.690.70.790.420.53Childhood health assessment questionnaire0.250.57-0.070.36-0.470.840.370.80.660.47 [ABSTRACT FROM PUBLISHER]

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.

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., Competing Interests: Competing interests: DE Research grants and consultancy fees from SOBI, Lilly, Pfizer; JA grants and consultancy fees from Novartis, Roche, Gebro Rest of authors no disclosures, (Copyright: © 2021 Desai Y et al.)

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., Competing Interests: Athimalaipet V Ramanan has received speaker fees/honoraria/consulting fees from Abbvie Inc. (North Chicago, IL, USA), Union Chimique Belge (Brussels, Belgium), Eli Lilly and Company (Indianapolis, IN, USA), Novartis (Basel, Switzerland), Roche Holding AG (Basel, Switzerland) and Bristol-Myers Squibb (New York, NY, USA). Paula R Williamson reports grants from the National Institute for Health Research (NIHR) Health Technology Assessment programme outside the submitted work and involvement with a clinical trials unit funded by NIHR.

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.

Introduction: Many children with juvenile idiopathic arthritis (JIA) continue to have active disease into adulthood. Adults with JIA are a heterogeneous group, and the effects of tumour necrosis factor inhibitor (TNFi) therapies are not well described. This analysis aims to describe treatment outcomes among patients with JIA starting TNFi for the first time in adulthood., Methods: Patients with arthritis onset <16 years starting their first TNFi therapy were identified from the British Society of Rheumatology Biologics Register. Disease activity outcomes (using 28-joint Disease Activity Score (DAS28) and Health Assessment Questionnaire (HAQ)) are presented at 1 year after start of therapy according to disease pattern. Incidence rates (IR) of adverse events per 1000 person-years (pyrs) were calculated. Outcomes in patients with polyarticular JIA were compared with a cohort (weighted for age and gender) of patients with rheumatoid arthritis (RA)., Results: In 443 adults with JIA starting a first TNFi, disease activity over 1 year improved across all measures. There were 58 first serious infections (IR 22.3/1000 pyrs); 4 cardiovascular events (IR 1.4/1000 pyrs); 11 uveitis events (IR 4.0/1000 pyrs) and 16 malignancies (IR 3.9/1000 pyrs). Compared with the weighted RA cohort, disease activity improvement was similar; malignancy rates were lower and uveitis rates much higher. While crude IR were similar, JIA patients had a lower risk of serious infection (HR 0.5 (95% CI 0.3 to 0.9))., Conclusions: This is the largest study to describe disease activity and safety outcomes in adults with JIA receiving TNFi. Disease activity improved after 1 year in all disease patterns, suggesting TNFi is an effective therapy in this population., Competing Interests: Conflicts of Interest: None declared.