Publications by authors named "Jon Giles"
Rationale: Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples.
Objective: Determine whether genetic and serological biomarkers of RA risk in combination with the (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans.
Objective: There are limited data on researchers' attitudes and beliefs on returning and managing incidental research findings from whole body F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) imaging.
Methods: Site principal investigators (PIs) who enrolled participants for the Treatments Against Rheumatoid Arthritis and Effect on FDG PET/CT (TARGET) trial were surveyed.
Results: Of the 28 TARGET site PIs eligible for the study, 18 consented to participate (response rate: 64%).
Background: Cardiovascular disease (CVD) is the main cause of mortality in Rheumatoid Arthritis (RA).
Objective: To investigate the effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) on lipids and CVD risk and evaluate associations with changes in systemic inflammation.
Methods: Patients with RA initiating a bDMARD were evaluated at baseline, 3 and 6 months later.
Background: Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk.
Methods: In this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks.
Objectives: Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. We studied whether a multi-biomarker panel for RA disease activity (MBDA) would associate with changes in arterial inflammation in an interventional trial.
Methods: In the TARGET Trial, RA patients with active disease despite methotrexate were randomly assigned to the addition of either a TNF inhibitor or sulfasalazine+hydroxychloroquine (triple therapy).
The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis.
Proc Natl Acad Sci U S A
April 2024
Although anti-citrullinated protein autoantibodies (ACPAs) are a hallmark serological feature of rheumatoid arthritis (RA), the mechanisms and cellular sources behind the generation of the RA citrullinome remain incompletely defined. Peptidylarginine deiminase IV (PAD4), one of the key enzymatic drivers of citrullination in the RA joint, is expressed by granulocytes and monocytes; however, the subcellular localization and contribution of monocyte-derived PAD4 to the generation of citrullinated autoantigens remain underexplored. In this study, we demonstrate that PAD4 displays a widespread cellular distribution in monocytes, including expression on the cell surface.
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- The study aimed to compare cardiovascular risks in patients with rheumatoid arthritis (RA) receiving tofacitinib versus tumor necrosis factor inhibitors (TNFi).
- It involved patients aged 50 and over with CV risk factors, evaluating rates of major adverse cardiovascular events (MACE) and various individual cardiovascular outcomes.
- The results indicated that while the overall risk of composite CV events was similar for both treatments, tofacitinib 10 mg was linked to a higher risk of certain outcomes compared to TNFi, particularly venous thromboembolism (VTE).
Unlabelled: Cardiovascular disease remains an important comorbidity in patients with rheumatoid arthritis (RA), but traditional models do not accurately predict cardiovascular risk in patients with RA. The addition of biomarkers could improve prediction.
Methods And Results: The TARGET (Treatments Against RA and Effect on FDG PET/CT) trial assessed whether different treatment strategies in RA differentially impact cardiovascular risk as measured by the change in arterial inflammation on arterial target to background ratio on fluorodeoxyglucose positron emission tomography/computed tomography scans conducted 24 weeks apart.
Objectives: Galectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA).
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- - Upadacitinib (UPA) is a JAK inhibitor effective for moderate-to-severe rheumatoid arthritis, showing a good safety profile in clinical trials that analyzed laboratory parameter changes.
- - The study pooled data from six trials involving over 3200 patients, revealing changes in blood counts and liver enzymes, with most adverse events, like anemia and neutropenia, occurring at similar rates compared to other treatments.
- - Overall findings indicate that UPA has long-term safety and efficacy, with very few patients discontinuing treatment due to lab-related issues.
Purpose: To determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate response.
Methods: This is a secondary analysis of the Rheumatoid Arthritis Comparison of Active Treatments (RACAT) trial and the (TEAR) trial. Both studies compared treatment strategies starting with conventional disease-modifying anti-rheumatic drugs (DMARDs) (triple therapy) versus etanercept plus methotrexate.
Background: Cardiovascular (CV) risk estimation calculators for the general population underperform in patients with rheumatoid arthritis (RA). The purpose of this study was to identify relevant protein biomarkers that could be added to traditional CV risk calculators to improve the capacity of coronary artery calcification (CAC) prediction in individuals with RA. In a second step, we quantify the improvement of this prediction of CAC when these circulating biomarkers are added to standard risk scores.
View Article and Find Full Text PDFJAK inhibitors and black box warnings: what is the future for JAK inhibitors?
Expert Rev Clin Immunol
November 2023
Introduction: Janus kinase inhibitors (JAKi) have dramatically improved the treatment of various autoimmune and myeloproliferative disorders. Recently, concern has arisen regarding their safety in patients with rheumatoid arthritis.
Areas Covered: Here, we provide a comprehensive summary of the major current and emerging JAKi and their indications, address recent studies on comparative safety, and provide insight into their future and use.
Article Synopsis
- * In a study involving 158 RA patients without clinical HF, it was found that left ventricular (LV) remodeling prevalence increased from 40% at baseline to 60% over a follow-up period of 4 to 6 years.
- * Higher interleukin-6 (IL-6) levels were linked to concentric LV remodeling, indicating its potential as a biomarker, while the medication tocilizumab was associated with baseline LV remodeling; future research is needed on IL-6's role in
The association between chronic inflammation and increased risk of cardiovascular disease in rheumatoid arthritis (RA) is well established. In the general population, inflammation is an established independent risk factor for cardiovascular disease, and much interest is placed on controlling inflammation to reduce cardiovascular events. As inflammation encompasses numerous pathways, the development of targeted therapies in RA provides an opportunity to understand the downstream effect of inhibiting specific pathways on cardiovascular risk.
View Article and Find Full Text PDFObjective: Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent.
Methods: Patients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks.
Article Synopsis
- The study aimed to assess the risk of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA) taking tofacitinib compared to those using tumor necrosis factor inhibitors (TNFi), particularly focusing on individuals with or without a history of atherosclerotic cardiovascular disease (ASCVD).
- Results indicated that tofacitinib users had a higher risk of MACE, myocardial infarction, and sudden cardiac death compared to TNFi, especially in patients with a history of ASCVD.
- Although MACE risk for tofacitinib was not significantly different in patients without ASCVD, the analysis concluded that further investigation is needed due to its exploratory nature and limited statistical power.
Objective: Examination and conventional radiography of joints are unable to precisely evaluate and measure disease activity in rheumatoid arthritis (RA). We quantified joint inflammation using F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in people with RA to determine if PET-derived uptake variables were correlated with RA disease activity measures.
Methods: We cross-sectionally studied 34 patients with RA in a substudy of the Rheumatoid Arthritis Study of the Myocardium (RHYTHM).
Article Synopsis
- Diastolic dysfunction (DD) is frequently seen in rheumatoid arthritis (RA) patients, with prevalence increasing from 40.7% at baseline to 57.9% after 4-6 years.
- A study of 158 RA patients without existing cardiovascular disease found that high RA disease activity at baseline was linked to higher rates of DD.
- Future research should investigate how changes in diastolic function relate to heart failure and whether treatment with disease-modifying antirheumatic drugs (DMARDs) can mitigate these effects.
Article Synopsis
- Lumbar spinal stenosis (LSS) surgery often involves the resection of ligamentum flavum, and this study examined the potential presence of transthyretin (TTR) amyloid in older patients, which could be a modifiable factor in LSS cases.
- In a study of 47 older adults undergoing lumbar spine decompression, amyloid was found in 34% of participants, with a higher prevalence in those aged 75 and older.
- The study identified TTR as the precursor protein in a majority of amyloid cases, but clinical and quality-of-life measures did not show significant differences between patients with or without amyloid.
Objective: To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).
Methods: We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.
Objective: To develop updated guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).
Methods: We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.