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Background: For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to biosimilars. Here, we aimed to investigate those who switched from an anti-tumour necrosis factor (TNF) originator to a biosimilar, regarding drug survival and disease activity, compared with a matched cohort who continued the originator., Methods: This analysis included all patients in the UK JIA Biologics Register switching directly from an anti-TNF originator to a biosimilar of the same product. All patients were matched (age, sex, disease duration, calendar year of when patients started originator therapy, line of therapy, and International League of Associations for Rheumatology [ILAR] category) to patients continuing the originator. For those matched successfully, a Cox proportional hazard model assessed whether drug persistence differed between those who switched compared with those who continued the originator. Overall change in the 71-joint juvenile arthritis disease activity score and the proportion of patients with a clinically important worsening score (by ≥1·7 units) after 6 months was compared between cohorts. This analysis was designed to address a priority research area set by our patient partners., Findings: There were 224 children and young people with non-systemic JIA (139 [62%] were female, and 85 [38%] were male) identified as switching from a biological originator to a biosimilar of the same product from Jan 1, 2017, to July 7, 2023. 143 (64%) patients were originally on adalimumab, 56 (25%) on etanercept, and 25 (11%) on infliximab. Of these, 164 patients were matched successfully to those continuing the originator. There was no evidence that patients switching were more likely to stop treatment compared with those continuing the originator, with a hazard ratio of 1·46 (95% CI 0·93-2·30). Of the 51 patients in the biosimilar group who stopped treatment, 18 (35%) switched back to the originator (14 in the first year), 28 (55%) started a different biological drug, and five (10%) discontinued all treatment by the last follow-up. Of the 87 matched patients with available disease activity, there was no evidence that JADAS-71 worsened more after 6 months, with an odds ratio of 0·71 (95% CI 0·34-1·51; p=0·38)., Interpretation: In this matched comparative effectiveness analysis, children and young people with JIA switched from originators to biosimilars. Disease activity was similar between patients switching compared with those continuing the originator. Three quarters of patients were still receiving their biosimilar after 1 year, with switching back to originator uncommon, at only 9% after 1 year, suggesting good tolerability of non-medical switching in this patient population. This information is reassuring to clinicians and patients regarding the effect of non-medical biological switching., Funding: British Society for Rheumatology, Versus Arthritis, and National Institutes for Health Research Manchester Biomedical Research Centre., Competing Interests: Declaration of interests KLH reports honoraria from AbbVie and grants from Pfizer and Bristol Myers Squibb unrelated to this manuscript; and is supported by the National Institutes for Health Research (NIHR), Manchester Biomedical Research Centre (NIHR203308). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The primary objective was to define the incidence of JSLE in children <16 years of age in the UK and Republic of Ireland (ROI). The secondary objective was to describe presenting features, classification criteria, initial management and disease damage in newly presenting JSLE patients., Methods: A prospective JSLE epidemiological study was undertaken between September 2017 and September 2019 with support of the British Paediatric Surveillance Unit and other professional groups involved in diagnosis and management of JSLE patients. Treating consultants reported all cases of JSLE seen. A follow-up study at 1 year examined management and progression of disease and treatment., Results: There were 124 incident cases included in the final analysis. Incidence was estimated using ACR-1997 classification criteria (0.36/100 000), SLICC-2012 classification criteria (0.41/100 000) and clinician expert opinion (0.46/100 000). A high disease burden was seen, with 71.0% of patients requiring ongoing systemic CS treatment at 1 year; 98.2% receiving immunomodulatory treatment; and 20.4% accruing damage in the year following diagnosis (predominantly neuropsychiatric-related), with substantial involvement from multiple speciality teams., Conclusions: The minimum UK and ROI incidence of JSLE is between 0.36 and 0.46/100 000, depending on the case definition used. Challenges in classification of patients with JSLE are highlighted, but overall this study supports the use of SLICC-2012 classification criteria. The high levels of disease damage and ongoing CS use 1 year after diagnosis is concerning, highlighting the need for further interventions to improve outcomes in JSLE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In the absence of clinical trials evidence, Juvenile-onset Systemic Lupus Erythematosus (JSLE) treatment plans vary., Aim: To explore 'real world' treatment utilising longitudinal UK JSLE Cohort Study data., Methods: Data collected between 07/2009-05/2020 was used to explore the choice/sequence of immunomodulating drugs from diagnosis. Multivariate logistic regression determined how organ-domain involvement (pBILAG-2004) impacted treatment choice., Result: 349 patients met inclusion criteria, median follow-up 4-years (IQR:2,6). Mycophenolate mofetil (MMF) was most commonly used for the majority of organ-domains, and significantly associated with renal involvement (OR:1.99, 95% CI:1.65-2.41, p c  < 0.01). Analyses assessing the sequence of immunomodulators focused on 197/349 patients (meeting relevant inclusion/exclusion criteria). 10/197 (5%) solely recieved hydroxychloroquine/prednisolone, 62/197 (31%) received a single-immunomodulator, 69/197 (36%) received two, and 36/197 patients (28%) received ≥three immunomodulators. The most common first and second line immunomodulator was MMF. Rituximab was the most common third-line immunomodulator., Conclusions: Most UK JSLE patients required ≥two immunomodulators, with MMF used most commonly., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To define the incidence and prevalence of Behçet's syndrome (BS) in children and young people (CYP) up to the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI)., Methods: A prospective epidemiological study was undertaken with the support of the British Paediatric Surveillance Unit (BPSU) and the British Society of Paediatric Dermatologists (BSPD). Consultants reported anonymised cases of BS seen. A follow-up study at one year examined progression of disease and treatment., Results: Over a two-year period, 56 cases met the International Criteria for Behçet's Disease. For children under 16 years of age, the two-year period prevalence estimate was 4.2 per million (95% CI: 3.2, 5.4) and the incidence was 0.96 per million person years (95% CI: 0.66, 1.41). Mucocutaneous disease was the most common phenotype (56/100%), with ocular (10/56; 17.9%), neurological (2/56; 3.6%) and vascular involvement (3/56; 5.4%) being less common. Median age at onset was 6.34 years and at diagnosis was 11.72 years. There were slightly more female than male children reported (32/56; 55.6%). The majority of cases (85.7%) were white Caucasian. Apart from genital ulcers, which were more common in females, there were no significant differences in frequency of manifestations between male or females, nor between ethnicities. Over 83% of cases had three or more non-primary care healthcare professionals involved in their care., Conclusion: BS is extremely rare in CYP in the UK and ROI and most have mucocutaneous disease. Healthcare needs are complex, and coordinated care is key., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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 × 10 9 /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.

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.

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.

Objectives: To describe and compare the occurrence of newly diagnosed uveitis in children with JIA receiving MTX, etanercept, adalimumab and infliximab., Methods: This on-drug analysis included patients within UK JIA registries (British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study and Biologics for Children with Rheumatic Diseases) with non-systemic disease, registered at MTX or biologic start with no history of uveitis. Follow-up began from date of first treatment, continuing until first uveitis, discontinuation of registered drug, most recent follow-up up or death, whichever came first. Hazard ratios comparing risk of uveitis between drugs were calculated using propensity-adjusted Cox regression., Results: A total of 2294 patients were included (943 MTX, 304 adalimumab/infliximab, 1047 etanercept). There were 44 reported cases of uveitis (27 MTX, 16 etanercept, 1 adalimumab). Unadjusted hazard ratio showed a reduced risk of uveitis in biologic cohorts compared with MTX. After adjusting for propensity deciles, there was no significant difference in the risk of uveitis between patients receiving etanercept or MTX [hazard ratio 0.5 (0.2-1.1)]. Fully adjusted comparisons were not possible for adalimumab/infliximab as there were too few events., Conclusions: In this first paper to compare the rate of new onset uveitis across the three main anti-TNF therapies used in JIA, a new diagnosis of uveitis is less common among patients starting biologics compared with MTX, although this did not reach statistical significance. The suggested protective effect of etanercept is likely explained by confounding, whereby patients in the MTX cohort are younger and earlier in disease, and therefore at greater risk of developing uveitis compared with etanercept patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15-20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study., Methods: Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years) and adolescent (14-18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up., Results: A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4-20] vs. 7(3-13] vs. 7(3-14], respectively, p  = 0.015] with increased activity in the following BILAG domains: mucocutaneous ( p  = 0.025), musculoskeletal ( p  = 0.029), renal ( p  = 0.027) and cardiorespiratory ( p  = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive ( p  = 0.034) and exhibited higher anti-dsDNA titres ( p  = 0.001). Pre-pubertal individuals less frequently presented with leukopenia ( p  = 0.002), thrombocytopenia ( p  = 0.004) or low complement ( p  = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up., Conclusions: Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and "classic" autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

Background: Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC)., Methods: UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann-Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis., Results: Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4-8 and 10-14 months post-renal biopsy and last follow-up, in terms of renal British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141-390) days after MMF treatment, and 151 (117-305) days following IVCYC ( p = 0.17). Time to renal flare was 451 (157-1266) days for MMF, and 343 (198-635) days for IVCYC ( p = 0.47)., Conclusion: This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.

Purpose: To report on the composition and performance of the portfolio of Ophthalmology research studies in the United Kingdom's National Institute for Health Research (NIHR) Clinical Research Network (UK CRN)., Methods: Ophthalmology studies open to recruitment between 1 April 2010 and 31 March 2018 were classified by: sub-specialty, participant age, gender of Chief Investigator, involvement of genetic investigations, commercial/ non-commercial, interventional/observational design. Frequency distributions for each covariate and temporal variation in recruitment to time and target were analysed., Results: Over 8 years, 137,377 participants were recruited (average of 15,457 participants/year; range: 5485-32,573) with growth by year in proportion of commercial studies and hospital participation in England (76% in 2017/18). Fourteen percent of studies had a genetic component and most studies (82%) included only adults. The majority of studies (41%) enrolled patients with retinal diseases, followed by glaucoma (17%), anterior segment and cataract (13%), and ocular inflammation (6%). Overall, 68% of non-commercial studies and 55% of commercial studies recruited within the anticipated time set by the study and also recruited to or exceeded the target number of participants., Conclusions: High levels of clinical research activity, growth and improved performance have been observed in Ophthalmology in UK over the past 8 years. Some sub-specialties that carry substantial morbidity and a very high burden on NHS services are underrepresented and deserve more patient-centred research. Yet the NIHR and its CRN Ophthalmology National Specialty Group has enabled key steps in achieving the goal of embedding research into every day clinical care.

Background: Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira ® ; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined., Objective: To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA., Design: This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost-utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out., Setting: The setting was tertiary care centres throughout the UK., Participants: Patients aged 2-18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks)., Interventions: All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months., Main Outcome Measures: Primary outcome - time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome - incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol., Results: A total of 90 participants were randomised (adalimumab, n  = 60; placebo, n  = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p  < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events., Conclusions: Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold., Future Work: A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified., Trial Registration: Current Controlled Trials ISRCTN10065623 and European Clinical Trials Database number 2010-021141-41., 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. 23, No. 15. See the NIHR Journals Library website for further project information. This trial was also funded by Arthritis Research UK (grant reference number 19612). Two strengths of adalimumab (20 mg/0.8 ml and 40 mg/0.8 ml) and a matching placebo were manufactured by AbbVie Inc. (the Marketing Authorisation holder) and supplied in bulk to the contracted distributor (Sharp Clinical Services, Crickhowell, UK) for distribution to trial centres., Competing Interests: Athimalaipet V Ramanan reports grants from the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme and Arthritis Research UK during the conduct of the study and others from AbbVie Inc. (Ludwigshafen, Germany) and the University Hospitals Bristol NHS Foundation Trust, outside the submitted work. He has received speaker fees from AbbVie Inc. and lectured in symposia, sponsored by AbbVie Inc.. He has also been on an Advisory Board organised by AbbVie Inc. and has been supported by AbbVie Inc. to attend European and American Rheumatology Society meetings. Andrew D Dick reports other from data and revenue sharing outside the submitted work for consultancy work, paid to University of Bristol by AbbVie Inc., Ashley P Jones, Andrew McKay, Anna Rosala-Hallas, Ben Hardwick, Helen Hickey, Naomi Rainford, Graeme Hickey, Ruwanthi Kolamunnage-Dona and Paula R Williamson report grants from the NIHR HTA programme and Arthritis Research UK during the conduct of the study, other from AbbVie Inc. and University Hospitals Bristol NHS Foundation Trust and personal fees from University of Liverpool, outside the submitted work. In addition, Paula R Williamson is the Director of the Clinical Trials Research Centre, which is the Clinical Trials Unit that managed the day-to-day running of this trial. Dyfrig Hughes and Patricia Woo report grants from the NIHR HTA programme and Arthritis Research UK during the conduct of the study and other from AbbVie Inc., outside the submitted work. Giovanna Culeddu and Eifiona Wood report grants from Arthritis Research UK during the conduct of the study. Sandrine Compeyrot-Lacassagne reports grants from the NIHR HTA programme and Arthritis Research UK during the conduct of the study, and grants and others from AbbVie Inc., outside the submitted work. Clive Edelsten reports grants from the NIHR HTA programme and Arthritis Research UK during the conduct of the study, and others and personal fees from AbbVie Inc., outside the submitted work. Michael W Beresford reports grants from the NIHR HTA programme and Arthritis Research UK during the conduct of the study and others from AbbVie Inc. and the University Hospitals Bristol NHS Foundation Trust, outside the submitted work.

Background and Objectives: The multisystem involvement and variable course of juvenile-onset systemic lupus erythematosus (JSLE) make it difficult to assess disease activity over time. International consensus definitions of inactive disease and clinical remission have been proposed. The aim of this study was to determine the proportion of patients meeting these criteria in a large national cohort of JSLE patients and the association between achieving inactive disease and clinical remission with disease activity at presentation and time to diagnosis., Methods: Patients diagnosed with JSLE aged ≤17 years with a minimum of 12 months follow-up participating in the UK JSLE Cohort Study were assessed against these criteria at baseline, 1 year and final clinic visit., Results: A total of 218 patients with mean follow-up duration of 4.7 years were included and analyzed at baseline visit, of which 93 and 209 were available for analysis at the 1-year and the last follow-up visits, respectively. Eighty-five percent at 1 year and 62% at final follow-up still had active disease while only 6% and 9%, respectively, achieved inactive disease according to the proposed criteria. The majority of patients continued to require immunosuppressive treatment despite their prolonged follow-up with only two patients achieving clinical remission on medication and none off medication. A large number of patients did not meet the criteria for inactive disease due to isolated laboratory abnormalities such as reduced lymphocyte count. Isolated low lymphocyte count was the reason for not fulfilling the inactive disease criteria in 20/79 (25%) patients at 1 year and 14/130 (11%) patients at final follow-up visit. No statistically significant differences in relation to time to diagnosis and disease activity at presentation were found between patients achieving inactive disease compared to those who did not, at 1 year and final follow-up., Conclusion: The majority of patients failed to achieve the proposed criteria for inactive disease and continued to require immunosuppressive treatment. This reflects the high burden of disease in JSLE despite immunosuppressive therapy. A significant proportion of patients had isolated laboratory abnormalities of potentially limited clinical significance, suggesting that some modifications of the proposed criteria may be required.

Purpose: To investigate the cost effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with juvenile idiopathic arthritis (JIA)., Design: A cost-utility analysis based on a clinical trial and decision analytic model., Participants: Children and adolescents 2 to 18 years of age with persistently active uveitis associated with JIA, despite optimized methotrexate treatment for at least 12 weeks., Methods: The SYCAMORE (Randomised controlled trial of the clinical effectiveness, SafetY and Cost effectiveness of Adalimumab in combination with MethOtRExate for the treatment of juvenile idiopathic arthritis associated uveitis) trial (identifier, ISRCTN10065623) of methotrexate (up to 25 mg weekly) with or without fortnightly administered adalimumab (20 or 40 mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment., Main Outcome Measures: Medical costs to the National Health Service in the United Kingdom, utility of defined health states, quality-adjusted life-years (QALYs), and incremental cost per QALY., Results: Adalimumab in combination with methotrexate resulted in additional costs of £39 316, with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129 025 per QALY gained. The probability of cost effectiveness at a threshold of £30 000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost effective., Conclusions: Adalimumab is clinically effective in uveitis associated with JIA; however, its cost effectiveness is not demonstrated compared with methotrexate alone in the United Kingdom setting., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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

Background: Juvenile-onset systemic lupus erythematosus (JSLE) patients may develop lupus nephritis (LN) during their initial presentation, or later in their disease. This study aimed to assess whether clinical/demographic factors characterize patients with LN within the United Kingdom JSLE Cohort Study, and whether such factors predict subsequent LN development., Methods: Univariate logistic regression modelling compared clinical/demographic factors in patients with and without LN at baseline. For those who subsequently developed LN, Cox proportional-hazard modelling was used to test the association between such factors and time to LN development. Covariates with p < 0.2 univariately were included within a multiple-regression model., Results: A total of 121/331 (37%) patients presented with active LN at baseline, with first American College of Rheumatology (ACR) score ( p < 2.0 × 10 -16 ), severe hypertension ( p = 0.0006), proteinuria ( p < 2.0 × 10 -16 ), creatinine ( p = 1.0 × 10 -16 ), erythrocyte sedimentation rate ( p = 1.0 × 10 -16 ), neutrophils ( p < 2.0 × 10 -16 ), complement 3 (C3) ( p = 4.0 × 10 -16 ) and ethnicity ( p = 3.0 × 10 -13 ) differing between those with and without LN. Of the 210 individuals without active LN at baseline, 13 patients had a single visit and were excluded from further analysis. Thirty-four of 197 (17%) developed LN after a median of 2.04 years (interquartile range, 0.8-3.7), with higher ACR scores ( p = 0.014 , hazard ratio (HR) = 1.45, 95% confidence interval (CI) = 1.08-1.95) and lower C3 levels ( p = 0.0082 , HR = 0.27, 95% CI = 0.10-0.68) demonstrated as predictors of subsequent LN., Conclusions: Clinical and demographic factors can help to characterize patients at increased risk of LN.

Background: Juvenile dermatomyositis (JDM) is a rare but severe autoimmune inflammatory myositis of childhood. International collaboration is essential in order to undertake clinical trials, understand the disease and improve long-term outcome. The aim of this study was to propose from existing collaborative initiatives a preliminary minimal dataset for JDM. This will form the basis of the future development of an international consensus-approved minimum core dataset to be used both in clinical care and inform research, allowing integration of data between centres., Methods: A working group of internationally-representative JDM experts was formed to develop a provisional minimal dataset. Clinical and laboratory variables contained within current national and international collaborative databases of patients with idiopathic inflammatory myopathies were scrutinised. Judgements were informed by published literature and a more detailed analysis of the Juvenile Dermatomyositis Cohort Biomarker Study and Repository, UK and Ireland., Results: A provisional minimal JDM dataset has been produced, with an associated glossary of definitions. The provisional minimal dataset will request information at time of patient diagnosis and during on-going prospective follow up. At time of patient diagnosis, information will be requested on patient demographics, diagnostic criteria and treatments given prior to diagnosis. During on-going prospective follow-up, variables will include the presence of active muscle or skin disease, major organ involvement or constitutional symptoms, investigations, treatment, physician global assessments and patient reported outcome measures., Conclusions: An internationally agreed minimal dataset has the potential to significantly enhance collaboration, allow effective communication between groups, provide a minimal standard of care and enable analysis of the largest possible number of JDM patients to provide a greater understanding of this disease. This preliminary dataset can now be developed into a consensus-approved minimum core dataset and tested in a wider setting with the aim of achieving international agreement.

Objective: The objective of this study was to investigate factors that may influence the interval between symptom onset and JSLE diagnosis., Methods: Data from all patients recruited to the UK JSLE Cohort Study between 2006 and 2011 and meeting ACR criteria for lupus were analysed. Variables associated with time between symptom onset and diagnosis were identified using correlation tests. Linear regression was used to identify independent predictors of access to care., Results: Two hundred and fifty-seven children with JSLE were included in the analysis (216 females, 41 males, ratio 5.3:1). The median time from symptom onset to diagnosis was 0.4 years (range 0.0-14.1 years, interquartile range 0.2-1.4). A linear regression model identified being of African or Caribbean origin (P = 0.006), Asian (P = 0.045), referred by a paediatrician (P = 0.047) or having nephritis (P = 0.045) at presentation as independent predictors of shorter time to diagnosis. Being of Caribbean or Asian origin, compared with white, was associated with a 56% and 37% reduction in geometric mean time to diagnosis, respectively. Similarly, being referred to paediatric rheumatology by a paediatrician or having nephritis at presentation was also associated with a 32% and 36% reduction in geometric mean time to diagnosis, respectively., Conclusion: Within this national UK cohort, ethnic origin, initial source of referral and having lupus nephritis at presentation were strong predictors of the interval to establishing a diagnosis of JSLE.

Objective: The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort., Methods: Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE., Results: Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (P<0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P<0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1., Conclusion: The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen., (Copyright © 2012 by the American College of Rheumatology.)