Systematic literature review and meta-analysis informing the EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.

Background: Targeted therapies have been associated with potential risk of malignancy, which is a common concern in daily rheumatology practice in patients with inflammatory arthritis (IA) and a history of cancer.

Objectives: To perform a systematic literature review to inform a Task Force formulating EULAR points to consider on the initiation of targeted therapies in patients with IA and a history of cancer.

Methods: Specific research questions were defined within the Task Force before formulating the exact research queries with a librarian.

2024 EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.

Background: Potential associations between targeted therapies and a new cancer in patients with inflammatory arthritis (IA) and a previous malignancy are a frequent concern in daily rheumatology practice.

Objectives: To develop points to consider (PTC) to assist rheumatologists when initiating a targeted therapy in the context of a previous malignancy.

Methods: Following EULAR standardised operating procedures, a task force met to define the research questions for a systematic literature review and to formulate the overarching principles (OPs) and the PTC.

Metabolic Aging as an Increased Risk for Chronic Obstructive Pulmonary Disease.

Background/objectives: Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD.

Methods: Plasma from 5704 subjects from the Genetic Epidemiology of COPD study (COPDGene) and 2449 subjects from Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) were profiled using the Metabolon global metabolomics platform (1013 annotated metabolites). Post-bronchodilator spirometry measures of airflow obstruction (forced expiratory volume at one second (FEV)/forced vital capacity (FVC) < 0.

Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis.

Objectives: Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS).

Method: Pooled data from Phase 2 (NCT01786668; 04/2013-03/2015)/Phase 3 (NCT03502616; 06/2018-08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts).

Generating Real-World Evidence From the Excellence Network in Rheumatology.

Purpose: The Excellence Network in RheumatoloGY (ENRGY) was founded in 2021 and encompasses data from more than 700 private practice rheumatology providers throughout the United States, forming a practice-based research network (PBRN).

Methods: Electronic health record (EHR) data from participating practices are aggregated, including structured data (e.g.

Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes.

Among tobacco-exposed persons with preserved spirometry (TEPS), we previously demonstrated that different lung volume indices, specifically elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity-to-TLC (FRC/TLC), identify different lung disease characteristics in the COPDGene cohort. Determine differential disease characteristics and trajectories associated with the lung volume indices among TEPS in the SPIROMICS cohort. We categorized TEPS (n=814) by tertiles (low, intermediate, high) of TLC or residual volume-to-TLC (RV/TLC) derived from baseline CT images, and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]) versus high RV/TLC without high TLC ([RV/TLC]).

Comparative Effectiveness of Abaloparatide and Teriparatide in Women 50 Years of Age and Older: Update of a Real-World Retrospective Analysis.

Background: Abaloparatide and teriparatide are osteoanabolic treatments indicated for postmenopausal women and men with osteoporosis at high risk of fracture. In the Abaloparatide Comparator Trial In Vertebral Endpoints study, bone mineral density improvements were significantly greater with abaloparatide compared to teriparatide at the total hip and femoral neck. We conducted a retrospective claims study to examine the incidences of hip and nonvertebral fractures and cardiovascular events in women aged ≥50 years initiating abaloparatide or teriparatide therapy, expanding on a previous retrospective claims study.

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies.

Background: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

Methods: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets.

Disease response in rheumatoid arthritis across four biologic therapies associates with improvement in paraoxonase-1 activity and oxylipins.

Objective: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme, that has been implicated as a biomarker of cardiovascular risk in patients with rheumatoid arthritis (RA). We aimed to investigate how different biologic therapies affect levels of PON1 and oxylipins.

Methods: 1213 adult patients with RA in the Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions cohort study with moderate-to-high disease activity (Clinical Disease Activity Index (CDAI) >10) who initiated a new biologic (tocilizumab (TCZ), n=296; abatacept, n=374; tumour necrosis factor inhibitors, n=427; rituximab, n=116) were followed prospectively with serum specimens analysed for PON1 activity by arylesterase (ARYL), lactonase (LAC) and PON assays at baseline and after 6 months of biologic therapy.

Serum Immunoglobulin G Levels Are Associated with Risk for Exacerbations: An Analysis of SPIROMICS.

Rationale: Serum Immunoglobulin G (IgG) deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD) but it is unclear whether concentrations in the lower end of the normal range still confer risk.

Objectives: To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD.

Measurements And Main Results: Former and current smokers in SPIROMICS (n=1,497) were studied, n=1,026 with and n=471 at risk for COPD.

B cell immune repertoire sequencing in tobacco cigarette smoking, vaping, and chronic obstructive pulmonary disease in the COPDGene cohort.

Rationale: Cigarette smoking (CS) impairs B cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B cell activity is unclear.

Objective: To examine B cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, dual-use, COPD-related outcomes, and demographic factors.

Agreement of Medication Information Derived From EHR Data Compared to Medicare Insurance Claims: An Analysis of Biologic Disease-Modifying Antirheumatic Drugs.

Purpose: Few studies have reported the agreement between medication information derived from ambulatory EHR data compared to administrative claims for high-cost specialty drugs. We used data from a national EHR-enabled registry, the Rheumatology Informatics System for Effectiveness (RISE), with linked Medicare claims in a population of patients with rheumatoid arthritis (RA) to investigate variations in agreement for different biologic disease-modifying agents (bDMARDs) between two data sources (RISE EHR data vs. Medicare claims), categorized by drug, route of administration, and patient insurance factors (dual eligibility).

Epidural Steroid Injections and Fracture Incidence Among Older Individuals with Radiculopathy.

Epidural steroid injections (ESIs) are a common and often effective treatment for radicular back pain. While oral glucocorticoids increase fracture incidence, little is known regarding fracture risk after ESI. This study investigated the incidence of fractures among individuals who received ESI and those who did not.

Using causal diagrams within the Grading of Recommendations, Assessment, Development and Evaluation framework to evaluate confounding adjustment in observational studies.

Background And Objectives: The current Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system instructs appraisers to evaluate whether individual observational studies have sufficiently adjusted for confounding. However, it does not provide an explicit, transparent, or reproducible method for doing so. This article explores how implementing causal graphs into the GRADE framework can help appraisers and end-users of GRADE products to evaluate the adequacy of confounding control from observational studies.

Early Improvements with Guselkumab Associate with Sustained Control of Psoriatic Arthritis: Post hoc Analyses of Two Phase 3 Trials.

Introduction: Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA).

Methods: Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve).

Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial.

Background: Patients hospitalised for COVID-19 are at risk for multiorgan failure and death. Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiovascular and kidney protection in patients with cardiometabolic conditions and could provide organ protection during COVID-19. We aimed to investigate whether SGLT2 inhibitors can reduce the need for organ support in patients hospitalised for COVID-19.

Dynamic and prognostic proteomic associations with FEV decline in chronic obstructive pulmonary disease.

Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.

Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression.

Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung.