Identification of Adult Dermatomyositis Patients Using Real-World Data Sources.

Objective: Studying rare diseases like dermatomyositis (DM) in single-center cohorts is challenging due to small sample sizes and limited generalizability. This study develops and evaluates case identification algorithms for DM to enable coordinated analysis across multiple data sources.

Methods: Case identification algorithms were developed to identify adult DM patients within eleven independent electronic health record or claims databases, totaling over 800 million patients, using the Observational Medical Outcomes Partnership (OMOP) Common Data Model.

Validation of Lung Ultrasound Interpretation Criteria for Interstitial Lung Disease in Systemic Sclerosis and Inflammatory Myopathy.

Objective: Interstitial lung disease (ILD) has a high prevalence in patients with systemic sclerosis (SSc) and inflammatory myopathy (IM), and early identification reduces associated morbidity and mortality. We previously developed lung ultrasound (LUS) interpretation criteria for ILD detection in 2020 (LUS-ILD-20) showing excellent sensitivity and specificity in patients with SSc-ILD; herein, we sought to validate a revised LUS-ILD-24 in a large cohort with SSc and IM.

Methods: Patients meeting criteria for SSc and IM, with planned computed tomography (CT) chest imaging underwent LUS imaging interpreted with LUS-ILD-24 by three blinded readers.

The role of multicriteria decision analysis in the development of candidate classification criteria for antisynthetase syndrome: analysis from the CLASS project.

Objectives: To develop and evaluate the performance of multicriteria decision analysis (MCDA)-driven candidate classification criteria for antisynthetase syndrome (ASSD).

Methods: A list of variables associated with ASSD was developed using a systematic literature review and then refined into an ASSD key domains and variables list by myositis and interstitial lung disease (ILD) experts. This list was used to create preferences surveys in which experts were presented with pairwise comparisons of clinical vignettes and asked to select the case that was more likely to represent ASSD.

Autoantibody hotspots reveal origin and impact of immunogenic XIST ribonucleoprotein complex.

Four out of five patients with autoimmune diseases are women. The XIST ribonucleoprotein (RNP) complex, comprising the female-specific long noncoding RNA XIST and over 100 associated proteins, may drive several autoimmune diseases that disproportionately affect women, who have elevated levels of autoantibodies against the XIST RNP. However, the structural distribution, potential origin, and clinical significance of XIST RNP autoantibodies remained unexplored.

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

TLR7/8 Activation in Immune Cells and Muscle by RNA-Containing Immune Complexes: Role in Inflammation and the Pathogenesis of Myositis.

Objective: Activation of endosomal toll-like receptors (TLRs) is one possible driver of inflammation in idiopathic inflammatory myopathies (IIM). We investigated the potential contribution of TLR7 and TLR8 to IIM pathogenesis.

Methods: Activation of TLR7/8 in healthy donor peripheral blood mononuclear cells (PBMCs) by immune complexes from patients with IIMs and lupus was tested.

SOX-5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women.

Objective: Adaptive immunity mediates psoriatic disease pathogenesis. We aimed to identify novel psoriatic autoantigens and their phenotypic associations in deeply characterized patient cohorts.

Methods: Sera from psoriatic arthritis (PsA) patients were used for autoantibody discovery.

International exchange on the clinical practice and research of rheumatic skin diseases: A report of the 5th International Conference of Cutaneous Lupus Erythematosus.

The 5th International Conference of Cutaneous Lupus Erythematosus was held in Tokyo, Japan on May 9 and 10, 2023. The latest topics on the pathogenesis, diagnosis, assessment, and treatment of cutaneous lupus erythematosus, dermatomyositis, and scleroderma (systemic sclerosis, morphea) were presented by experts in each field and new developments discussed. In these rheumatic skin diseases, many clinical trials of novel therapies targeting cytokines, signaling molecules, plasmacytoid dendritic cells, B cells, and other molecules are currently underway, and standardization of outcome assessment was discussed.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017.

Novel therapeutic targets in dermatomyositis.

Dermatomyositis (DM) is a systemic autoimmune disease with variable clinical presentations, including inflammation in the skin, muscle, lungs, and/or joints. Current therapeutic strategies in DM typically include broad immunosuppression; however, the currently used modalities are not universally effective and are associated with various side effects, including risk of infection. There is currently a highly unmet need for more effective and well-tolerated therapies.

Xist ribonucleoproteins promote female sex-biased autoimmunity.

Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation.

The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis.

Objective: The type 1 interferon (IFN) pathway is up-regulated in dermatomyositis (DM). We sought to define how organ-specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic type I IFN activity in adult patients with DM.

Methods: RNA sequencing was performed on 355 whole blood samples collected from 202 well-phenotyped DM patients followed up during the course of their clinical care.

Performance of the 2016 ACR-EULAR Myositis Response Criteria in adult dermatomyositis/polymyositis therapeutic trials and consensus profiles.

Objective: The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening.

Methods: Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated.

Association of Anti-CCAR1 Autoantibodies With Decreased Cancer Risk Relative to the General Population in Patients With Anti-Transcriptional Intermediary Factor 1γ-Positive Dermatomyositis.

Objective: To describe the disease specificity, clinical phenotype, and risk of cancer in dermatomyositis (DM) patients with autoantibodies against cell division cycle and apoptosis regulator protein 1 (anti-CCAR1).

Methods: The frequency of anti-CCAR1 autoantibodies was measured by enzyme-linked immunosorbent assay in the serum of DM patients from 2 independent cohorts (Johns Hopkins and Stanford), with patients with several other rheumatic diseases and healthy controls used as comparators. Clinical features and the risk of cancer incidence relative to that in the general population were determined in anti-CCAR1-positive DM patients.