Search

Objectives: Childhood-onset systemic lupus erythematosus (cSLE), representing 15%-20% of individuals with SLE, has been difficult to study globally due to differences between registries. This initiative, supported by Childhood Arthritis Rheumatology Research Alliance (CARRA) and Paediatric Rheumatology European Society (PReS), aims to create Core and Expanded cSLE Datasets to standardise and enhance research worldwide., Methods: 21 international cSLE experts and 4 patients participated in a Delphi process (questionnaires, 2 topic-specific focus groups and 3 virtual consensus meetings) to create 2 standardised cSLE datasets. The Core cSLE Dataset was designed to include data essential to meaningful clinical research across many settings. The Expanded cSLE Dataset was designed for centres able to consistently collect data to address broader research questions. Final data items for the Core and Expanded datasets were determined by consensus defined as >80% agreement) using an adapted nominal group technique and voting., Results: The resulting Core cSLE Dataset contains 46 items, including demographics, clinical features, laboratory results, medications and significant adverse events. The Expanded cSLE Dataset adds 26 additional items and includes patient-reported outcomes. Consensus was also achieved regarding the frequency and time points for data collection: baseline, quarterly follow-up visits, annually and flare visits., Conclusion: Standardised Core and Expanded cSLE Datasets for registry-based international cSLE research were defined through the consensus of global experts and patient/caregiver representatives, endorsed by CARRA and PReS. These datasets incorporate disease-specific and patient-specific features, optimised for diverse settings to facilitate international collaborative research for children and adolescents with SLE worldwide., (Copyright © 2024 European Alliance of Associations for Rheumatology (EULAR). Published by Elsevier B.V. All rights reserved.)

Objectives: Application of 'treat-to-target' (T2T) in childhood-onset systemic lupus erythematosus (cSLE) may improve care and health outcomes. This initiative aimed to harmonise existing evidence and expert opinion regarding T2T for cSLE., Methods: An international T2T Task Force was formed of specialists in paediatric rheumatology, paediatric nephrology, adult rheumatology, patient and parent representatives. A steering committee formulated a set of draft overarching principles and points-to-consider, based on evidence from systematic literature review. Two on-line preconsensus meeting Delphi surveys explored healthcare professionals' views on these provisional overarching principles and points-to-consider. A virtual consensus meeting employed a modified nominal group technique to discuss, modify and vote on each overarching principle/point-to-consider. Agreement of >80% of Task Force members was considered consensus., Results: The Task Force agreed on four overarching principles and fourteen points-to-consider. It was agreed that both treatment targets and therapeutic strategies should be subject to shared decision making with the patient/caregivers, with full remission the preferred target, and low disease activity acceptable where remission cannot be achieved. Important elements of the points-to-consider included: aiming for prevention of flare and organ damage; glucocorticoid sparing; proactively addressing factors that impact health-related quality of life (fatigue, pain, mental health, educational challenges, medication side effects); and aiming for maintenance of the target over the long-term. An extensive research agenda was also formulated., Conclusions: These international, consensus agreed overarching principles and points-to-consider for T2T in cSLE lay the foundation for future T2T approaches in cSLE, endorsed by the Paediatric Rheumatology European Society., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Lupus nephritis (LN) occurs in 50%-60% of patients with childhood-onset systemic lupus erythematosus (cSLE), leading to significant morbidity. Timely recognition of renal involvement and appropriate treatment are essential to prevent renal damage. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative aimed to generate diagnostic and management regimens for children and adolescents with rheumatic diseases including cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of childhood LN. Recommendations were developed using the European League Against Rheumatism standard operating procedures. A European-wide expert committee including paediatric nephrology representation formulated recommendations using a nominal group technique. Six recommendations regarding diagnosis and 20 recommendations covering treatment choices and goals were accepted, including each class of LN, described in the International Society of Nephrology/Renal Pathology Society 2003 classification system. Treatment goal should be complete renal response. Treatment of class I LN should mainly be guided by other symptoms. Class II LN should be treated initially with low-dose prednisone, only adding a disease-modifying antirheumatic drug after 3 months of persistent proteinuria or prednisone dependency. Induction treatment of class III/IV LN should be mycophenolate mofetil (MMF) or intravenous cyclophosphamide combined with corticosteroids; maintenance treatment should be MMF or azathioprine for at least 3 years. In pure class V LN, MMF with low-dose prednisone can be used as induction and MMF as maintenance treatment. The SHARE recommendations for diagnosis and treatment of LN have been generated to support uniform and high-quality care for all children with SLE., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, multisystem and potentially life-threatening autoimmune disorder with significant associated morbidity. Evidence-based guidelines are sparse and management is often based on clinical expertise. SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimise and disseminate management regimens for children and young adults with rheumatic diseases like cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of cSLE. In view of extent and complexity of cSLE and its various manifestations, recommendations for lupus nephritis and antiphospholipid syndrome will be published separately. Recommendations were generated using the EULAR (European League Against Rheumatism) standard operating procedure. An expert committee consisting of paediatric rheumatologists and representation of paediatric nephrology from across Europe discussed evidence-based recommendations during two consensus meetings. Recommendations were accepted if >80% agreement was reached. A total of 25 recommendations regarding key approaches to diagnosis and treatment of cSLE were made. The recommendations include 11 on diagnosis, 9 on disease monitoring and 5 on general treatment. Topics included: appropriate use of SLE classification criteria, disease activity and damage indices; adequate assessment of autoantibody profiles; secondary macrophage activation syndrome; use of hydroxychloroquine and corticosteroid-sparing regimens; and the importance of addressing poor adherence. Ten recommendations were accepted regarding general diagnostic strategies and treatment indications of neuropsychiatric cSLE. The SHARE recommendations for cSLE and neuropsychiatric manifestations of cSLE have been formulated by an evidence-based consensus process to support uniform, high-quality standards of care for children with cSLE., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Antiphospholipid syndrome (APS) is rare in children, and evidence-based guidelines are sparse. Consequently, management is mostly based on observational studies and physician's experience, and treatment regimens differ widely. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative was launched to develop diagnostic and management regimens for children and young adults with rheumatic diseases. Here, we developed evidence-based recommendations for diagnosis and treatment of paediatric APS. Evidence-based recommendations were developed using the European League Against Rheumatism standard operating procedure. Following a detailed systematic review of the literature, a committee of paediatric rheumatologists and representation of paediatric haematology with expertise in paediatric APS developed recommendations. The literature review yielded 1473 articles, of which 15 were valid and relevant. In total, four recommendations for diagnosis and eight for treatment of paediatric APS (including paediatric Catastrophic Antiphospholipid Syndrome) were accepted. Additionally, two recommendations for children born to mothers with APS were accepted. It was agreed that new classification criteria for paediatric APS are necessary, and APS in association with childhood-onset systemic lupus erythematosus should be identified by performing antiphospholipid antibody screening. Treatment recommendations included prevention of thrombotic events, and treatment recommendations for venous and/or arterial thrombotic events. Notably, due to the paucity of studies on paediatric APS, level of evidence and strength of the recommendations is relatively low. The SHARE initiative provides international, evidence-based recommendations for diagnosis and treatment for paediatric APS, facilitating improvement and uniformity of care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

To develop standards and recommendations for transitional care for young people (YP) with juvenile-onset rheumatic and musculoskeletal diseases (jRMD). The consensus process involved the following: (1) establishing an international expert panel to include patients and representatives from multidisciplinary teams in adult and paediatric rheumatology; (2) a systematic review of published models of transitional care in jRMDs, potential standards and recommendations, strategies for implementation and tools to evaluate services and outcomes; (3) setting the framework, developing the process map and generating a first draft of standards and recommendations; (4) further iteration of recommendations; (5) establishing consensus recommendations with Delphi methodology and (6) establishing standards and quality indicators. The final consensus derived 12 specific recommendations for YP with jRMD focused on transitional care. These included: high-quality, multidisciplinary care starting in early adolescence; the integral role of a transition co-ordinator; transition policies and protocols; efficient communications; transfer documentation; an open electronic-based platform to access resources; appropriate training for paediatric and adult healthcare teams; secure funding to continue treatments and services into adult rheumatology and the need for increased evidence to inform best practice. These consensus-based recommendations inform strategies to reach optimal outcomes in transitional care for YP with jRMD based on available evidence and expert opinion. They need to be implemented in the context of individual countries, healthcare systems and regulatory frameworks., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To determine association of erythrocyte methotrexate polyglutamates (MTX-PG) with disease activity and adverse effects in a prospective juvenile idiopathic arthritis (JIA) cohort., Methods: One hundred and thirteen JIA patients were followed from MTX start until 12 months. Erythrocyte MTX-PGs with 1-5 glutamate residues were measured at 3 months with tandem mass spectrometry. The outcomes were Juvenile Arthritis Disease Activity Score (JADAS)-27 and adverse effects. To determine associations of MTX-PGs with JADAS-27 at 3 months and during 1 year of MTX treatment, linear regression and linear mixed-model analyses were used. To determine associations of MTX-PGs with adverse effects during 1 year of MTX treatment, logistic regression was used. Analyses were corrected for JADAS-27 at baseline and co-medication., Results: Median JADAS-27 decreased from 12.7 (IQR: 7.8-18.2) at baseline to 2.9 (IQR: 0.1-6.5) at 12 months. Higher concentrations of MTX-PG3 (β: -0.006, p=0.005), MTX-PG4 (β: -0.015, p=0.004), MTX-PG5 (β: -0.051, p=0.011) and MTX-PG3-5 (β: -0.004, p=0.003) were associated with lower disease activity at 3 months. Higher concentrations of MTX-PG3 (β: -0.005, p=0.028), MTX-PG4 (β: -0.014, p=0.014), MTX-PG5 (β: -0.049, p=0.023) and MTX-PG3-5 (β: -0.004, p=0.018) were associated with lower disease activity over 1 year. None of the MTX-PGs was associated with adverse effects., Conclusions: In the first prospective study in JIA, long-chain MTX-PGs were associated with lower JADAS-27 at 3 months and during 1 year of MTX treatment. Erythrocyte MTX-PG could be a plausible candidate for therapeutic drug monitoring of MTX in JIA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Autoinflammatory disorders are disorders of the innate immune system. Standard genetic testing provided no correct diagnosis in a female patient from a non-consanguineous family of British descent with a colchicine-responsive autosomal dominant periodic fever syndrome. We aimed to unravel the genetic cause of the symptoms., Methods: Whole exome sequencing was used to screen for novel sequence variants, which were validated by direct Sanger sequencing. Ex vivo stimulation with peripheral blood mononuclear cells was performed to study the functional consequences of the mutation. mRNA and cytokine levels were measured by quantitative PCR and ELISA, respectively., Results: Whole exome sequencing revealed a novel missense sequence variant, not seen in around 6800 controls, mapping to exon 8 of the MEFV gene (c.1730C>A; p.T577N), co-segregating perfectly with disease in this family. Other mutations at the same amino acid (c.1730C>G; p.T577S and c.1729A>T; p.T577S) were found in a family of Turkish descent, with autosomal dominant inheritance of familial Mediterranean fever (FMF)-like phenotype, and a Dutch patient, respectively. Moreover, a mutation (c.1729A>G; p.T577A) was detected in two Dutch siblings, who had episodes of inflammation of varying severity not resembling FMF. Peripheral blood mononuclear cells from one patient of the index family showed increased basal interleukin 1β mRNA levels and cytokine responses after lipopolysaccharide stimulation. Responses normalised with colchicine treatment., Conclusions: Heterozygous mutations at amino acid position 577 of pyrin can induce an autosomal dominant autoinflammatory syndrome. This suggests that T577, located in front of the C-terminal B30.2/SPRY domain, is crucial for pyrin function.

Objective: To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure., Methods: The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates., Results: Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patient-years of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent., Conclusions: Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category.