Elicitation of expert prior opinion to design the BARJDM trial in juvenile dermatomyositis.

OBJECTIVES: To elicit and quantify expert opinion concerning the relative merits of two treatments for a rare inflammatory disease: Juvenile dermatomyositis (JDM). The formal expression of expert opinion reported in this paper will be used in a Bayesian analysis of a forthcoming randomised controlled trial known as BARJDM (baricitinib for juvenile dermatomyositis). METHODS: A Bayesian prior elicitation meeting was convened, following a previously described methodological template. Opinion was sought on the probability that a patient in the BARJDM trial would achieve clinically inactive disease, off glucocorticoids (GC) within a 12-month period with either methotrexate (standard of care); or baricitinib (a Janus kinase inhibitor, JAKi), with GC schedules identical in both arms of the trial. Experts' views were discussed and refined following presentation and further discussion of summated published data regarding efficacy of methotrexate or JAKi for JDM. RESULTS: Ten UK paediatric rheumatology consultants (including one adolescent paediatric rheumatologist) participated in the elicitation meeting. All had expertise in JDM, leading active National Health Service clinics for this disease. Consensus expert prior opinion was that the most likely probability of clinically inactive disease off GC within 12 months was 0.55 on baricitinib and 0.23 on methotrexate, with a greater degree of uncertainty for baricitinib. CONCLUSION: Experts currently think that baricitinib is superior to MTX for the treatment of JDM, although there is uncertainty around this. BARJDM will therefore integrate randomised trial data with this expert prior opinion to derive a posterior distribution for the relative efficacy of baricitinib compared with MTX.

National recommendations for the management of children and young people with IgA vasculitis: a best available evidence, group agreement-based approach.

OBJECTIVE: IgA vasculitis (IgAV) is the most frequently experienced subtype of vasculitis seen in children. Most children fully recover, however, complications including chronic kidney disease are recognised. The aim of this project was to use a best available evidence, group agreement, based approach to develop national recommendations for the initial management of IgAV and its associated complications. METHODS: A fully representative multiprofessional guideline development group (GDG), consisting of 28 members, was formed and met monthly. Graded recommendations were generated using nationally accredited methods, which included a predefined scope, open consultation, systematic literature review, evidence appraisal, review of national or international guidelines and a period of open consultation. Audit measures and research priorities were incorporated. RESULTS: The IgAV GDG met over a 14-month period. A total of 82 papers were relevant for evidence synthesis. For the initial management, four topic areas were identified with five key questions generating six graded recommendations related to classification, specialist referral and musculoskeletal involvement. For the associated complications, five topic areas with 12 key questions generated 15 graded recommendations covering nephritis, gastrointestinal and testicular involvement, atypical disease and follow-up. Open consultation feedback was incorporated. The guidelines were endorsed by the UK Kidney Association and Royal College of Paediatrics and Child Health and are available online. CONCLUSION: Despite IgAV being a rare disease with limited evidence, a national standardised approach to the clinical management for children and young people has been achieved. This should unite approaches to care and act as a foundation for improvement.

Pediatric Sarcoidosis: Retrospective Analysis of Biopsy-Proven Patients.

OBJECTIVE: To describe the phenotype, disease course, and treatment of a large cohort of children with sarcoidosis. METHODS: Patients with biopsies consistent with sarcoidosis, performed between 2010 and 2020, were included in this study. Patients' notes were reviewed retrospectively. Children with disease onset before 5 years of age were compared with older children. Regression analysis was performed to determine predictors of treatment outcome. RESULTS: In total, 48 children with a mean age at diagnosis of 9.5 years, with a male to female ratio of 0.71, were identified. In total, 72% of the children were of Black race and 94% had multiorgan disease, with an average of 4.8 organs involved, most commonly lymph nodes (65%), skin (63%), and eyes (60%). Laboratory findings of note included raised serum calcium in 23% of patients and raised angiotensin-converting enzyme in 76% of patients. Out of 14 patients tested, 6 had mutations in NOD2. In total, 81% of patients received systemic steroids and 90% received conventional disease-modifying antirheumatic drugs (DMARDs); in 25% of patients, a biologic was added, mostly anti-tumor necrosis factor (anti-TNF). Although most patients could be weaned off steroids (58%), most remained on long-term DMARDs (85%). Children under the age of 5 years presented more often with splenomegaly (P = 0.001), spleen involvement (P = 0.003), and higher C-reactive protein (P = 0.10). Weight loss was more common in adolescents (P = 0.006). Kidney (P = 0.004), eye (P = 0.005), and liver involvement (P = 0.03) were more common in Black patients. Regression analysis identified no single factor associated with positive treatment outcomes. CONCLUSION: Multiorgan involvement, response to steroids, and chronic course are hallmarks of pediatric sarcoidosis. The phenotype significantly varies by age and race. Where conventional DMARDs were not efficacious, the addition of an anti-TNF agent was beneficial.