A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: Initial 3-months results of the BeSt for Kids-study

Background: Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study. Methods: Included patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported. Results: 94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ. After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported. Conclusion: After 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy. Trial registration:NTR1574. Registered 3 December 2008

Endothelial and Inflammation Biomarker Profiles at Diagnosis Reflecting Clinical Heterogeneity and Serving as a Prognostic Tool For Treatment Response in Two Independent Cohorts of Patients With Juvenile Dermatomyositis

Objective: Juvenile dermatomyositis (DM) is a heterogeneous systemic immune-mediated vasculopathy. This study was undertaken to 1) identify inflammation/endothelial dysfunction–related biomarker profiles reflecting disease severity at diagnosis, and 2) establish whether such biomarker profiles could be used for predicting the response to treatment in patients with juvenile DM. Methods: In total, 39 biomarkers related to activation of endothelial

Dutch juvenile idiopathic arthritis patients, carers and clinicians create a research agenda together following the James Lind Alliance method: A study protocol

Background: Research on Juvenile Idiopathic Arthritis (JIA) should support patients, caregivers/parents (carers) and clinicians to make important decisions in the consulting room and eventually to improve the lives of patients with JIA. Thus far these end-users of JIA-research have rarely been involved in the prioritisation of future research. Main body: Dutch organisations of patients, carers and clinicians will collaboratively develop a research agenda for JIA, following the James Lind Alliance (JLA) methodology. In a 'Priority Setting Partnership' (PSP), they will gradually establish a top 10 list of the most important unanswered research questions for JIA. In this process the input from clinicians, patients and their carers will be equally valued. Additionally, focus groups will be organised to involve young people with JIA. The involvement of all contributors will be monitored and evaluated. In this manner, the project will contribute to the growing body of literature on how to involve young people in agenda setting in a meaningful way. Conclusion: A JIA research agenda established through the JLA method and thus co-created by patients, carers and clinicians will inform researchers and research funders about the most important research questions for JIA. This will lead to research that really matters

Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of diseaseResearch in context

Summary: Background: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. Methods: Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. Findings: ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C. Interpretation: Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. Funding: The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication