Real-world utilisation and switching between Janus kinase inhibitors in Australian patients with rheumatoid arthritis in the OPAL dataset.

Objectives: To describe use and treatment persistence for Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) by line of therapy, and the mechanism of action for the drug switched to after JAKi discontinuation.

Methods: This was a retrospective, observational analysis using the OPAL dataset, a large collection of deidentified electronic medical records from 112 rheumatologists around Australia. Adult patients with RA were included if they initiated tofacitinib (TOF), baricitinib (BARI) or upadacitinib (UPA) between 1 October 2015 and 30 September 2021.

Comparative effectiveness of etanercept originator and biosimilar for treating rheumatoid arthritis: implications for cost-savings.

Background And Aims: This study aimed to assess the comparative effectiveness of the etanercept (ETN) originator (Enbrel) and ETN biosimilar SB4 (Brenzys) as first-line treatment in patients with rheumatoid arthritis (RA), while also exploring the potential cost-savings associated with this approach in Australia.

Methods: Clinical data were obtained from the Optimising Patient outcomes in rheumatoLogy Australian real-world data set. Adult patients with RA who had initiated treatment with the ETN originator or biosimilar as their first-recorded biologic or targeted synthetic disease-modifying antirheumatic drug between 1 April 2017 and 31 December 2020 were included.

The impact of immunocompromise on outcomes of COVID-19 in children and young people-a systematic review and meta-analysis.

Background: Despite children and young people (CYP) having a low risk for severe coronavirus disease 2019 (COVID-19) outcomes, there is still a degree of uncertainty related to their risk in the context of immunodeficiency or immunosuppression, primarily due to significant reporting bias in most studies, as CYP characteristically experience milder or asymptomatic COVID-19 infection and the severe outcomes tend to be overestimated.

Methods: A comprehensive systematic review to identify globally relevant studies in immunosuppressed CYP and CYP in general population (defined as younger than 25 years of age) up to 31 October 2021 (to exclude vaccinated populations) was performed. Studies were included if they reported the two primary outcomes of our study, admission to intensive therapy unit (ITU) and mortality, while data on other outcomes, such as hospitalization and need for mechanical ventilation were also collected.

Burden of disease and real-world treatment patterns of patients with systemic lupus erythematosus in the Australian OPAL dataset.

Objective: To describe the demographics, disease burden and real-world management of patients with systemic lupus erythematosus (SLE) in Australian community practice.

Methods: Patients with a physician diagnosis of SLE and at least 1 visit between 1 January 2009 and 31 March 2021 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 112 Australian rheumatologists. Demographics, basic clinical features and prescribed medications were described, with medication combinations used as a surrogate of disease severity.

Comparative Effectiveness of First-Line Baricitinib in Patients With Rheumatoid Arthritis in the Australian OPAL Data Set.

Objective: To analyze comparative treatment persistence for first-line baricitinib (BARI) versus first-line tumor necrosis factor inhibitor (TNFi) in patients with rheumatoid arthritis (RA) and for first-line BARI initiated as monotherapy versus first-line BARI initiated with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD).

Methods: Patients with RA who initiated BARI or TNFi as first-line biologic or targeted synthetic DMARD from October 1, 2015, to September 30, 2021, were identified in the OPAL data set. Drug survival times to 6, 12, and 24 months were analyzed using restricted mean survival time (RMST).

A novel electronic patient-reported outcome delivery system to implement health-related quality of life measures in routine clinical care: An analysis of 5 years of experience.

Objective: To develop a simple and secure technological solution to incorporate electronic patient-reported outcomes (ePROs) into routine clinical care.

Methods: A novel ePRO questionnaire delivery system was developed by Software for Specialists (S4S) in partnership with OPAL Rheumatology Australia. Validated questionnaires were sent from the electronic medical record (EMR) (Audit4) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), lupus or giant cell arteritis (GCA) and delivered to the patient's email address or completed in the clinic waiting room using a smart device (in-practice).

Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis.

Objectives: To define the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM).

Methods: RNA-sequencing was performed on CD4, CD8, CD14 and CD19 cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, on-treatment n=11) and age/sex-matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC). Mitochondrial morphology and superoxide were assessed by fluorescence microscopy, cellular metabolism by C glucose uptake assays, and oxidised mitochondrial DNA (oxmtDNA) content by dot-blot.

Association with HLA-DRβ1 position 37 distinguishes juvenile dermatomyositis from adult-onset myositis.

Juvenile dermatomyositis (JDM) is a rare, severe autoimmune disease and the most common idiopathic inflammatory myopathy of children. JDM and adult-onset dermatomyositis (DM) have similar clinical, biological and serological features, although these features differ in prevalence between childhood-onset and adult-onset disease, suggesting that age of disease onset may influence pathogenesis. Therefore, a JDM-focused genetic analysis was performed using the largest collection of JDM samples to date.

JAK inhibitors: a potential treatment for JDM in the context of the role of interferon-driven pathology.

Juvenile Idiopathic Inflammatory Myopathies (IIM) are a group of rare diseases that are heterogeneous in terms of pathology that can include proximal muscle weakness, associated skin changes and systemic involvement. Despite options for treatment, many patients continue to suffer resistant disease and lasting side-effects. Advances in the understanding of the immunopathology and genetics underlying IIM may specify new therapeutic targets, particularly where conventional treatment has not achieved a clinical response.

A survey to understand the feelings towards and impact of COVID-19 on the households of juvenile dermato myositis patients from a parent or carer perspective.

Objectives: This aim of this study was to gain a better understanding of how parents and carers feel about the effects and impact of the coronavirus disease 2019 (COVID-19) pandemic lockdown and how this impacted upon their child/young person with JDM.

Method: We approached 139 participants from the JDM Cohort Biomarker Study (JDCBS), with specific consent to approach electronically for research studies. A secure electronic questionnaire with study introduction was sent to participants for their parents and carers around the UK to complete.

Favorable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases.

Background: Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained, and the effect of underlying immune dysfunction or suppression is unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and juvenile systemic lupus erythematosus (JSLE) against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group.

Methods: Sera were collected from JIA (n = 118), JDM (n = 49), and JSLE (n = 30) patients and from healthy control (n = 54) children and adolescents prior to the coronavirus disease 19 (COVID-19) pandemic.

Use of Rescue Therapy with IVIG or Cyclophosphamide in Juvenile Myositis.

Purpose Of Review: This review aims to present the literature available to date on the use of intravenous immunoglobulin and cyclophosphamide for juvenile patients with inflammatory myopathies, to evaluate the strength of the evidence so far for both these medications, and to reach conclusions about their efficacy.

Recent Findings: Juvenile idiopathic inflammatory myopathies, mainly represented by juvenile dermatomyositis (JDM), are rare diseases but quite debilitating for the patients. JDM is an autoimmune condition with predominantly muscle and skin involvement but also systemic features affecting the cardiovascular, respiratory, and gastrointestinal systems.

Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission.

Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.

Identification and prediction of novel classes of long-term disease trajectories for patients with juvenile dermatomyositis using growth mixture models.

Objectives: Uncertainty around clinical heterogeneity and outcomes for patients with JDM represents a major burden of disease and a challenge for clinical management. We sought to identify novel classes of patients having similar temporal patterns in disease activity and relate them to baseline clinical features.

Methods: Data were obtained for n = 519 patients, including baseline demographic and clinical features, baseline and follow-up records of physician's global assessment of disease (PGA), and skin disease activity (modified DAS).

Retrospective analysis of infliximab and adalimumab treatment in a large cohort of juvenile dermatomyositis patients.

Background: Anti-TNF treatment may be useful for the treatment of patients with refractory juvenile dermatomyositis (JDM). The aim of this study was to describe the use of infliximab and adalimumab therapy in juvenile dermatomyositis as an adjunctive treatment.

Methods: Sixty children recruited to the UK JDM Cohort and Biomarker Study that had received at least 3 months of anti-TNF treatment (infliximab or adalimumab) were studied.

Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups.

Objectives: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.

Galectin-9 and CXCL10 as Biomarkers for Disease Activity in Juvenile Dermatomyositis: A Longitudinal Cohort Study and Multicohort Validation.

Objective: Objective evaluation of disease activity is challenging in patients with juvenile dermatomyositis (DM) due to a lack of reliable biomarkers, but it is crucial to avoid both under- and overtreatment of patients. Recently, we identified 2 proteins, galectin-9 and CXCL10, whose levels are highly correlated with the extent of juvenile DM disease activity. This study was undertaken to validate galectin-9 and CXCL10 as biomarkers for disease activity in juvenile DM, and to assess their disease specificity and potency in predicting the occurrence of flares.

Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration.

Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present.

Systemic and Tissue Inflammation in Juvenile Dermatomyositis: From Pathogenesis to the Quest for Monitoring Tools.

Juvenile Dermatomyositis (JDM) is a systemic immune-mediated disease of childhood, characterized by muscle weakness, and a typical skin rash. Other organ systems and tissues such as the lungs, heart, and intestines can be involved, but may be under-evaluated. The inflammatory process in JDM is characterized by an interferon signature and infiltration of immune cells such as T cells and plasmacytoid dendritic cells into the affected tissues.

Clinical signs and symptoms in a joint model of four disease activity parameters in juvenile dermatomyositis: a prospective, longitudinal, multicenter cohort study.

Background: It is currently impossible to predict the prognosis of patients with juvenile dermatomyositis (JDM). The aim of this study was to find clinical features most strongly associated with outcome variables in JDM as a first step towards tailor-made treatment.

Methods: In a large, prospectively followed, multicenter cohort study of 340 patients with JDM, each contributing multiple visits, a Bayesian model of disease activity was developed, using the four continuous outcome variables creatine kinase (CK), childhood myositis assessment score (CMAS), manual muscle testing of 8 muscle groups (MMT8) and the physician's global assessment of disease activity (PGA).

CD19CD24CD38 B Cells Are Expanded in Juvenile Dermatomyositis and Exhibit a Pro-Inflammatory Phenotype After Activation Through Toll-Like Receptor 7 and Interferon-α.

Juvenile dermatomyositis (JDM) is a rare form of childhood autoimmune myositis that presents with proximal muscle weakness and skin rash. B cells are strongly implicated in the pathogenesis of the disease, but the underlying mechanisms are unknown. Therefore, the main objective of our study was to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in JDM patients.

Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling.

Objective: In patients with severe or refractory juvenile dermatomyositis (DM), second-line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of its efficacy in juvenile DM is limited. This study was undertaken to describe clinical improvement in juvenile DM patients treated with CYC and model the efficacy of CYC treatment compared to no CYC treatment.