Sarilumab in relapsing polymyalgia rheumatica: patient-reported outcomes from a phase 3, double-blind, randomised controlled trial.

Background: Sarilumab is approved for adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. We aimed to evaluate the effect of sarilumab on patient-reported outcomes.

Methods: This phase 3, double-blind, randomised controlled trial was done in 60 centres in 17 countries.

Finding influential cores via normalized Ricci flows in directed and undirected hypergraphs with applications.

Many biological and social systems are naturally represented as edge-weighted directed or undirected hypergraphs since they exhibit group interactions involving three or more system units as opposed to pairwise interactions that can be incorporated in graph-theoretic representations. However, finding influential cores in hypergraphs is still not as extensively studied as their graph-theoretic counterparts. To this end, we develop and implement a hypergraph-curvature guided discrete time diffusion process with suitable topological surgeries and edge-weight renormalization procedures for both undirected and directed weighted hypergraphs to find influential cores.

An innovative hybrid training method for ultrasound in giant cell arteritis, polymyalgia rheumatica and large vessel vasculitis.

We propose a novel hybrid physical and virtual training method, complemented by online learning, as an effective method to teach and acquire ultrasound skills. We aim to illustrate this through our experience with a remote ultrasound training module for giant cell arteritis scanning. The significance of this innovation is the ability to mitigate the challenges faced by ultrasound training during pandemic-times, including the need for physical distancing, group size limitation and overseas travel restrictions.

Population Pharmacokinetics and Exposure-Response Analyses of Sarilumab in Patients with Polymyalgia Rheumatica.

Sarilumab (interleukin-6 receptor inhibitor) is approved in the United States and Europe for polymyalgia rheumatica (PMR). This study characterized sarilumab pharmacokinetics (PK) and assessed the influence of intrinsic and extrinsic factors on PK in patients with PMR and giant cell arteritis (GCA). Exposure-responses analyses were conducted to evaluate the PK-pharmacodynamic (PD) relationships of sarilumab with key efficacy and safety endpoints in patients with PMR (NCT03600818).

GM-CSF drives IL-6 production by macrophages in polymyalgia rheumatica.

Objectives: Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR.

Reliability of the OMERACT Giant cell arteritis Ultrasonography Score (OGUS): results of a patient-based exercise involving experts and non-experts in vascular ultrasonography.

Objective: To test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography.

Methods: Six GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2.

Targeting interleukin-6 pathways in giant cell arteritis management: A narrative review of evidence.

Giant cell arteritis (GCA) is a chronic inflammatory vasculitis with a significant impact on vascular and patient health. It may present with non-specific symptoms and can lead to severe complications if not managed effectively. This narrative review explores the treatment of GCA with interleukin-6 (IL-6) pathway inhibitors, focusing on key studies from selected databases published between 2018 and 2024.

Symptom Severity and Glucocorticoid Dosing in Patients With Polymyalgia Rheumatica and Obesity.

Objective: Polymyalgia rheumatica (PMR) is an inflammatory disorder of the elderly characterized by girdle pain and stiffness. Obesity has an influence on disease activity and outcome in rheumatic diseases like osteoarthritis and rheumatoid arthritis. We aimed to investigate the relationship between high BMI and the severity and outcome of PMR, which is incompletely understood.

m6ATM: a deep learning framework for demystifying the m6A epitranscriptome with Nanopore long-read RNA-seq data.

N6-methyladenosine (m6A) is one of the most abundant and well-known modifications in messenger RNAs since its discovery in the 1970s. Recent studies have demonstrated that m6A is involved in various biological processes, such as alternative splicing and RNA degradation, playing an important role in a variety of diseases. To better understand the role of m6A, transcriptome-wide m6A profiling data are indispensable.

Integrating point-of-care ultrasound into rheumatology practice.

A scenario‑based probability approach integrating point‑of‑care rheumatology ultrasound (POCRUS) into rheumatology practice has recently been proposed as a teaching methodology to encourage greater awareness of US among practicing clinicians, especially with respect to the management of overlapping clinical conditions. This article reviews the rheumatological areas where application of POCRUS substantially enhances clinical reasoning to confirm or exclude target conditions. It highlights the definitions of US‑detected pathologies in rheumatoid arthritis, spondylarthritis, gout and crystal arthritis, osteoarthritis, and polymyalgia rheumatica, and discusses the added value of POCRUS in diagnosing these conditions.

Development of a diagnostic prediction model for giant cell arteritis by sequential application of Southend Giant Cell Arteritis Probability Score and ultrasonography: a prospective multicentre study.

Background: Giant cell arteritis is a critically ischaemic disease with protean manifestations that require urgent diagnosis and treatment. European Alliance of Associations for Rheumatology (EULAR) recommendations advocate ultrasonography as the first investigation for suspected giant cell arteritis. We developed a prediction tool that sequentially combines clinical assessment, as determined by the Southend Giant Cell Arteritis Probability Score (SGCAPS), with results of quantitative ultrasonography.

Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials.

Background: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status.

Methods: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe.

A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis.

Background: Giant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed beneficial effects in GCA, leading to its approval. This study investigated the efficacy and safety of sarilumab (another IL-6Ri) in GCA.

Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper.

Background: More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway.

Subclinical giant cell arteritis in polymyalgia rheumatica: Concurrent conditions or a common spectrum of inflammatory diseases?

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice.

Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

Objectives: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).

Methods: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting.

RNA Modification Detection Using Nanopore Direct RNA Sequencing and nanoDoc2.

RNA modifications regulate multiple aspects of cellular function including RNA splicing, translation, export, decay, stability, and phase separation. One of the comprehensive ways to detect such modifications is by the recent advancement of direct RNA sequencing from Oxford Nanopore Technologies (ONT). However, this method obtains a large amount of data with high complexity in the form of raw current signal that poses a new informatics challenge to accurately detect those modifications.

A hybrid approach to study large conformational transitions of biomolecules from single particle XFEL diffraction data.

X-ray free-electron laser (XFEL) is the latest generation of the X-ray source that could become an invaluable technique in structural biology. XFEL has ultrashort pulse duration, extreme peak brilliance, and high spatial coherence, which could enable the observation of the biological molecules in near nature state at room temperature without crystallization. However, for biological systems, due to their low diffraction power and complexity of sample delivery, experiments and data analysis are not straightforward, making it extremely challenging to reconstruct three-dimensional (3D) structures from single particle XFEL data.

Explicit versus implicit consideration of binding partners in protein-protein complex to elucidate intrinsic dynamics.

The binding of many proteins to their protein partners is tightly regulated via control of their relative intrinsic dynamics during the binding process, a phenomenon which can in turn be modulated. Therefore, investigating the intrinsic dynamics of proteins is necessary to understand function in a comprehensive way. By intrinsic dynamics herein, we principally refer to the vibrational signature of a protein molecule popularly obtained from normal modes or essential modes.

An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

Objectives: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment.

Methods: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research.