Long-term oral glucocorticoid use is associated with complications, healthcare resource utilization, and costs among patients with dermatomyositis or polymyositis.

Introduction/objective: Oral glucocorticoids (OGC) are conventionally used as first-line treatment for dermatomyositis (DM) and polymyositis (PM). This study evaluated clinical and economic outcomes associated with long-term (LT) OGC use in DM/PM.

Methods: Adults with ≥ 2 medical claims of DM/PM 30‒365 days apart from January 1, 2016, to December 31, 2022, and ≥ 1 diagnosis code of a physician specialty of interest were selected from the MarketScan Commercial and Medicare Supplemental databases.

Perioperative nivolumab or nivolumab plus ipilimumab in resectable diffuse pleural mesothelioma: a phase 2 trial and ctDNA analyses.

Immune checkpoint blockade (ICB) is standard of care in advanced diffuse pleural mesothelioma (DPM), but its role in the perioperative management of DPM is unclear. In tandem, circulating tumor DNA (ctDNA) ultra-sensitive residual disease detection has shown promise in providing a molecular readout of ICB efficacy across resectable cancers. This phase 2 trial investigated neoadjuvant nivolumab and nivolumab/ipilimumab in resectable DPM along with tumor-informed liquid biopsy residual disease assessments.

Design of Two Randomized, Placebo-Controlled, Phase 3 Trials of Deucravacitinib, an Oral, Selective, Allosteric TYK2 Inhibitor, in Systemic Lupus Erythematosus.

Background And Objectives: Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, demonstrated efficacy across the primary endpoint and all key secondary endpoints in the phase 2 PAISLEY SLE trial in patients with active systemic lupus erythematosus (SLE). Here, we describe 2 phase 3 trials [POETYK SLE-1 (NCT05617677), POETYK SLE-2 (NCT05620407)] which will assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and disease activity adjudication.

Radiomic biomarkers associated with immune checkpoint blockade response for advanced renal cell carcinoma.

Purpose: Immune checkpoint blockade (ICB) has transformed outcomes for patients with metastatic renal cell carcinoma (mRCC) and has impacted the timing and use of cytoreductive nephrectomy (CN). As ICB responses vary, we evaluated whether radiographic and radiomic biomarkers were associated with clinical and pathological outcomes.

Methods: This retrospective cohort study included ICB-treated mRCC patients without upfront CN.

Relapsed rhabdomyosarcoma: treatment recommendations from the European pediatric soft tissue sarcoma study group (EpSSG).

At least one-third of patients with localized rhabdomyosarcoma (RMS) and 60-70% of patients with metastatic RMS experience progressive disease or relapse. Following relapse, outcomes generally remain poor with limited treatment options and a high risk of subsequent recurrence. Optimal treatment requires a multidisciplinary approach incorporating chemotherapy with local control.

ERS/EULAR clinical practice guidelines for connective tissue diseases associated interstitial lung disease.

Background: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care.

Methods: A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies.

High transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy.

Background: Response to immune checkpoint inhibition (ICI) in sarcomas is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy and patient selection. Thus, we investigated whether the expression of transposable elements (TEs), which are epigenetically silenced and can stimulate antitumor immunity, influence ICI outcomes and immune infiltrates in common sarcoma subtypes.

Seizure-Related Homolog Protein 6 (SEZ6): Biology and Therapeutic Target in Neuroendocrine Carcinomas.

Seizure-related homolog protein 6 (SEZ6) is a cell surface type 1 transmembrane protein involved in neuronal development, expression of which in adult tissues is almost exclusively limited to the central nervous system. Aberrant expression of SEZ6 has been associated with neurodevelopmental and psychiatric disorders including epilepsy, schizophrenia, and Alzheimer's disease. More recently, SEZ6 overexpression has been detected in small cell lung cancer (SCLC) and other high-grade neuroendocrine malignancies, although our understanding of the function of SEZ6 as a driver of cancer is limited.

Persistent progression independent of relapse activity in multiple sclerosis.

Patients with relapsing-remitting multiple sclerosis (RRMS) may experience disability progression independent of relapse activity (PIRA), which can be an early sign of secondary progressive MS (SPMS). We defined persistent PIRA as ongoing sustained disability over the entire available follow-up period. However, PIRA events can regress over time.

ERS/EULAR clinical practice guidelines for connective tissue disease-associated interstitial lung diseaseDeveloped by the task force for connective tissue disease-associated interstitial lung disease of the European Respiratory Society (ERS) and the European Alliance of Associations for Rheumatology (EULAR)Endorsed by the European Reference Network on rare respiratory diseases (ERN-LUNG).

Background: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care.

Methods: A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies.

Target volume delineation of the neck for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, the Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology collaboratively developed evidence-based guidelines and a comprehensive contouring atlas for neck target volume delineation in nasopharyngeal carcinoma. These guidelines address five key challenges in modern radiotherapy practice: margin design of clinical target volume; nodal target volume delineation after induction chemotherapy; delineation of equivocal nodes evident on imaging; low-risk clinical target volume delineation based on regional stepwise extension patterns; and modifications for anatomical boundaries of lymphatic areas. Developed through a rigorous systematic review and expert appraisal process by a panel of 50 international, multidisciplinary members from 17 countries and regions, these guidelines incorporate the latest advances in nasopharyngeal carcinoma diagnosis and treatment.

Primary target volume delineation for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology jointly developed evidence-based guidelines and a contouring atlas for primary target volume delineation for radiotherapy in nasopharyngeal carcinoma. The guidelines systematically address three crucial challenges: margin design of clinical target volumes; target volume delineation after induction chemotherapy; and low-risk clinical target volume delineation based on local stepwise extension patterns. Based on a comprehensive systematic review and critical appraisal by an international multidisciplinary panel of 50 nasopharyngeal carcinoma specialists from 17 countries and regions, these guidelines are in keeping with advances in nasopharyngeal carcinoma diagnosis and treatment, embodying contemporary treatment concepts, and elaborating on the differences in practice.

Association of patient and physician characteristics with androgen-deprivation-therapy intensification in patients with de novo hormone-sensitive metastatic prostate cancer: A population-based study.

Introduction: Treatment intensification with androgen receptor signaling inhibitors and/or chemotherapy is guideline recommended for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). However, most patients only receive androgen deprivation therapy monotherapy. The aim was to identify physician-, patient-, and tumor-related factors associated with the receipt of treatment intensification.

Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial.

Importance: Effective and well-tolerated pharmacotherapies for generalized anxiety disorder (GAD), which is one of the most common psychiatric disorders, are needed.

Objective: To determine the dose-response relationship of MM120 (lysergide D-tartrate) in adults with moderate to severe GAD.

Design, Settings, And Participants: This phase 2b, multicenter, randomized, double-blind, placebo-controlled study enrolled 198 adults aged 18 to 74 years with a primary GAD diagnosis who presented with moderate to severe symptoms (defined by a Hamilton Anxiety Rating Scale [HAM-A] score ≥20) and was conducted at 22 outpatient psychiatric research sites in the US from August 2022 to August 2023.

A phase 1b/2 study of intermittent talazoparib plus temozolomide in patients with metastatic castration-resistant prostate cancer and no mutations in DNA damage response genes.

As monotherapy, PARP inhibitors have little cytotoxic effect in tumors without homologous recombinant repair (HRR) alterations. Supported by preclinical models, we hypothesized that the PARP inhibitor talazoparib in combination with temozolomide chemotherapy could induce DNA damage leading to cell death and tumor response in patients with metastatic castration-resistant prostate cancer (mCRPC) without HRR alterations. In this phase 1b/2 trial (NCT04019327; registration date July 11, 2019), patients with progressive mCRPC without HRR mutations who failed at least one androgen receptor signaling inhibitor were enrolled in escalating doses of intermittent talazoparib plus temozolomide to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) in Phase 1b.

Evaluation of Neutrophil to Lymphocyte Ratio in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Treated With a Combination of Cetuximab and Nivolumab in a Phase II Clinical Trial.

Objectives: We report on the biomarker analyses focusing on neutrophil-to-lymphocyte ratios (NLR) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with combined cetuximab and nivolumab.

Methods: Data were obtained from a phase II trial (NCT03370276). Peripheral blood NLR was obtained at baseline (B-NLR) and on-treatment (OT-NLR; 1 mo from treatment initiation).

A sensitive and specific non-invasive urine biomarker panel for prostate cancer detection.

Background: Prostate cancer (PCa) is one of the leading causes of cancer death in men. While prostate-specific antigen (PSA) testing is widely used for screening, its diagnostic accuracy is limited, often failing to distinguish between benign and malignant prostate conditions, underscoring the need for novel biomarkers with improved diagnostic performance. This study aimed to identify and validate a panel of urinary RNA biomarkers with improved diagnostic accuracy for PCa.

Item selection for the development and validation of a revised classification criteria for adult and juvenile idiopathic inflammatory myopathies: MyoROC project.

Objective: A revision of the 2017 EULAR-ACR myositis classification criteria, namely EULAR-ACR funded Myositis Revision of Classification (MyoROC) project, is currently underway involving a large international group of experts. In the first phase of this project, we identified additional items to be tested in the criteria.

Methods: We distributed an electronic survey to International Myositis Assessment and Clinical Studies (IMACS) members to identify new items.

Efficacy and Safety of Upadacitinib in Patients With Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results Through 140 Weeks.

Background: Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe atopic dermatitis (AD) in adults and adolescents; long-term efficacy and safety data beyond 1 year are needed.

Objective: The aim was to evaluate the long-term efficacy and safety of upadacitinib treatment through 140 weeks in patients with moderate-to-severe AD.

Methods: Measure Up 1 (MeUp1; NCT03569293), Measure Up 2 (MeUp2; NCT03607422), and AD Up (NCT03568318) are ongoing, phase 3, randomized clinical trials evaluating upadacitinib 15 mg (UPA15) and 30 mg (UPA30) in adults and adolescents with moderate-to-severe AD.

Perturbances in Both Circulating B and CD4 T Cells Discriminate Multiple Sclerosis from Other Central Nervous System Autoimmune Diseases.

Using spectral flow cytometry, we analyzed circulating lymphocyte subsets in treatment-naive individuals with multiple sclerosis (MS) and other central nervous system autoimmune diseases (CNS AIDs). Elevated B-cell and CD4 T-cell frequencies were a disease-specific feature of MS, while reduced T-bet and CXCR3 B-cell levels were associated with progressive disease.

Data Sharing Experience, Guidance, and Resources From the Rare Diseases Clinical Research Network (RDCRN).

The Rare Diseases Clinical Research Network (RDCRN) comprises research consortia and other partners focused on the study of rare diseases. Its goals include sharing de-identified data with the scientific community and other stakeholders to advance rare disease research. The RDCRN Data Use & Data Sharing Committee and RDCRN Data Management and Coordinating Center reviewed data sharing practices across established consortia and published literature to develop guidance documents.

Healthcare Resource Use, Healthcare Costs, and Unmet Needs Among Patients Treated for EGFR-Mutated Advanced or Metastatic Non-small Cell Lung Cancer.

Background: Approximately 17% of patients with non-small cell lung cancer (NSCLC) have epidermal growth factor receptor-mutated (EGFRm) NSCLC, 84% of which are exon 19 deletions (Ex19del)/exon 21 substitutions (L858R). Unmet needs for patients treated with tyrosine kinase inhibitors (TKIs) for EGFRm (Ex19del/L858R) advanced NSCLC, including osimertinib, are relevant to US population health decision makers.

Objectives: To describe healthcare resource utilization (HRU) and costs by line of therapy (LOT) among patients with EGFRm (Ex19del/L858R) advanced NSCLC initiating first-line (1L) treatment.

Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study.

Systemic sclerosis (SSc) is a chronic autoimmune disease with multi-organ involvement. Historically, SSc classification has focused on the type of skin involvement (limited versus diffuse); however, a growing evidence of organ-specific variability suggests the presence of more than two distinct subtypes. We propose a semi-supervised generative deep learning framework leveraging expert-driven definitions of organ-specific involvement and severity.