Giant Cell Arteritis (GCA)

Giant Cell Arteritis (GCA) is a vasculitis of medium- and large-sized arteries in older adults that may lead to serious vascular complications, including permanent vision loss and aortic aneurysm formation. Glucocorticoids are effective, but relapse during tapering is common and poses a major clinical challenge, potentially contributing to prolonged glucocorticoid exposure. Symptoms are often nonspecific and conventional inflammatory markers lack sufficient reliability, particularly in patients treated with drugs targeting the interleukin-6 pathway. Thus, this project aims to evaluate different tools assisting disease activity monitoring and/or predict future relapses and higher treatment requirements. Up to 175 patients with GCA in remission will be enrolled to ensure that 144 participants complete 1 year of follow-up. Participants undergo vascular ultrasonography, including double-blinded assessment at suspected relapse, complete patient-reported outcome measures, and provide biobank blood samples.

This is a multi-center, randomized, open label study that will assess the efficacy and safety of ACTEMRA(R) or one of its FDA-approved biosimilars Tocilizumab (TCZ) maintenance versus withdrawal in Giant cell arteritis (GCA) patients who are in remission after at least 12 months of high dose TCZ treatment. Eligible participants will also have discontinued glucocorticoids (e.g., prednisone (or equivalent)) entirely at least three months before randomization. High dose TCZ treatment includes 6-8 mg/kg intravenously (IV) monthly or 162 mg subcutaneously (SC) weekly, which are two forms of administration that are commonly used in clinical practice and are equally efficacious in controlling GCA This research study has three parts: 1. The screening phase (up to 42 days) consists of collecting information about your health and your GCA, a physical exam, and blood tests to see If you qualify to enroll in the study 2. The study treatment phase (withdrawal/step down dosing phase study months 0 - 18) consists of you either completely stopping or decreasing your current dose of tocilizumab while collecting information about your health and your GCA as well as blood samples every two months at clinic visits 3. The safety follow-up phase (months 19-30) consists of collecting information about your health and your GCA as well as blood samples every three months The primary objective is to determine the rate of disease relapse at 18 months in participants with GCA who receive low-dose TCZ compared to those who discontinue TCZ

We propose to analyze the kinetics of the main marker of inflammation in GCA in order to understand its links with initial clinical manifestations and the possible appearance of complications and/or relapses. Early assessment of the rate of CRP normalization would enable us to adapt the therapeutic strategy in order to avoid complications and/or relapses.

Giant cell arteritis (GCA) is a rare disease characterized by vasculitis of the large arterial trunks targeting the thoracic aorta and its dividing branches, affecting adults over the age of 50. Vasculitis lesions cause thickening of the arterial wall, visible on temporal artery biopsy (TAB) or vascular imaging (echo-Doppler, angio-CT, angio-MRI, 18FDG PET-CT). This is a severe disease that can lead to blindness. Early diagnosis is essential, so that steroids therapy can be started as soon as possible to prevent complications. Doppler ultrasonography of the temporal arteries provides rapid, non-invasive diagnostic support. However, the recommendations do not specify how soon temporal artery Doppler should be performed after steroids treatment, except that the halo sign would disappear after about 5 days on steroids. Sensitivity seems to be better when the examination is performed early, but the time taken for the halo sign to disappear is unknown. The investigator suggests that the disappearance of the temporal artery halo sign in GCA patients is observed earlier than D14 of steroids treatment usually reported in the literature. He speculates that the sensitivity of the temporal artery Doppler decreases as early as D3 of steroids treatment, and that beyond D7 it is not useful to perform this examination as its sensitivity becomes too low.

B cells are a component of the immune system which appear be important in causing all forms of cardiovascular disease. Until now, it has not been possible to directly study these cells in living patients (essential to assess their potential as the target of new treatments). For the first time in any cardiovascular disease, this study will apply cutting edge scanning technology to visualise B cells in the blood vessels of giant cell arteritis (GCA) patients. GCA is a common and potentially deadly disorder of the blood vessels which is caused by abnormalities of the immune system. Current treatments are mainly limited to steroids. Unfortunately, these drugs bring tremendous side effects and so there is an urgent requirement to discover alternatives. Laboratory investigations tell us that B cells are highly present in GCA and so if the proposed scanning technology fails to identify these cells in the blood vessels of participants, then the technology is unlikely to be useful for other cardiovascular diseases. If, however, the study does successfully visualise B cells, this knowledge could pave the way for clinical trials of B cell targeted treatments (already established in other conditions) as steroid alternatives in GCA. This study aims to map the distribution of the radiotracer zirconium-89 labelled rituximab within the blood vessels of patients with newly diagnosed GCA and compare this with two separate control groups without the condition. This will allow us to determine the role of B cells within this condition, and whether patients would benefit from B cell-depleting treatments such as rituximab.

Large vessel vasculitis (LVV) is an autoimmune inflammatory disorder affecting the major arteries of the body. The diagnosis and monitoring this condition can be challenging, as patients often present with symptoms that are unclear, and the diagnostic criteria currently used are varied. Accurate diagnosis is essential because it helps to tailor the treatment to each patient. Some treatments, such as steroids and immunosuppressive medications, can have significant side effects, so they need to be used carefully and only when truly needed. An \[18F\]FDG Positron Emission Tomography/Computed Tomography (PET/CT) involves the injection of a small amount of radiolabelled sugar, which assesses glucose metabolism within the body. \[18F\]FDG PET/CT is already used by the NHS to detect inflammation within the vessel walls and diagnose LVV. Current diagnostic criteria for LVV largely rely on visual assessment by a radiologist. This approach therefore has limitations and may not fully capture changes in the levels of inflammation over time. A new generation of scanners, known as Long Axial Field-of-View (LAFOV)-PET/CT or Total Body PET, are currently transforming what is possible in the field of medical imaging. These LAFOV-PET/CT scanners have new digital detectors that are more sensitive, produce sharper images, and can scan the entire body rapidly. This offers several potential advantages for patients with LVV, including the clearer detection of vessel wall inflammation, the ability to administer lower doses of the radiolabelled sugar (\[18F\]FDG), and the ability to take repeated pictures over time to measure subtle changes in blood flow and inflammation. Patients receiving a routine NHS \[18F\]FDG PET/CT scan for LVV are typically scanned 60 minutes after injection of the radiotracer using a standard PET/CT. Another benefit of LAFOV-PET/CT scanners is their ability to assess the amount of the radiolabelled sugar taken up by the whole body almost as soon as it is injected which could give important additional information. As part of the LAVA-FLOW study we are planning to combine LAFOV-PET/CT with a CT Angiogram (CTA) in patients with LVV. A CTA is a scan that shows doctors what your blood vessels look like. It involves the injection of a dye into a vein that makes your blood vessels visible, highlighting vessel wall inflammation and vessel wall narrowing. This combination of LAFOV-PET/CT and CTA therefore has the potential to give a much more detailed picture of LVV than is achievable using current methods. The LAVA-FLOW study therefore aims to develop a standardised protocol to be used in different hospital centres across the UK for the imaging of LVV using LAFOV-PET/CT. We also hope that the results of this particular study could lead to further larger studies with the potential to update the diagnostic criteria and improve the monitoring of this condition.

Giant cell arteritis (GCA) is an inflammation of the blood vessels. A dangerous complication is sudden vision loss due to insufficient blood supply to the optic nerve. However, it is often difficult to distinguish acute vision loss due to GCA from a similar condition of insufficient blood supply to the optic nerve, called NAION. Quick treatment with anti-inflammatory medication is needed in case of GCA to prevent vision loss on the eye and other serious complications. Patients with NAION have no benefit of the medication, but can have serious side effects, why it is very important to differentiate between these conditions. In this project, the investigators will use FDG PET/MRI with Black Blood (BB) sequences and OCT-imaging to study patients with GCA and/or ischemic optic nerve disease. The investigators will look for signs of inflammation in and around the small vessels of the orbit using PET/MRI and study subtle retinal changes using OCT images. The investigators want to answer the following research questions: Do patients with ischemic optic nerve disease and GCA show signs of inflammation in the orbital vessel wall on PET/MRI-scans, that are not present in patients with NAION? Do GCA patients without vision loss, but with signs of orbital vessel wall inflammation on PET/MRI-scans, have a higher risk of later vision loss than GCA patients without? Can subtle changes in the retina, detectable through OCT, help distinguish between GCA-related vision loss and NAION? This will, to our knowledge, be the first study to systematically use FDG PET/MRI BB-scans to illuminate vascular changes in the orbit of patients with GCA and/or ischemic optic nerve disease. The results may improve diagnosis and treatment of GCA and NAION in the future. The investigators hope that this will help prevent blindness and other serious complications in patients with GCA, while also avoiding unnecessary treatments for patients with NAION.

The purpose of this study is to determine whether a treatment with 3 months of bosentan associated to standard therapy might be superior to glucocorticoids alone in term of failure free survival at 12 months

The GISCO study plans to determine whether 8-week therapy is just as effective as 26-week cortisone therapy for treating giant cell arteritis * with tocilizumab, * while using less cortisone.

Giant cell arteritis (GCA) is the most common vasculitis in the elderly and is usually treated with long-term corticosteroid therapy. Many patients experience relapses and treatment-related side effects. Current diagnostic and monitoring methods provide limited prognostic information and cannot reliably distinguish active from inactive disease during relapse. This project addresses the clinical need for improved tools to identify patients at high risk of relapse and to develop more effective methods for disease monitoring. The aim is to develop new tools that enable more personalized treatment of GCA. By combining vascular ultrasound with novel blood biomarkers, we seek to predict disease course and relapse risk. The specific objectives are: * To identify ultrasound and blood biomarkers that can predict long-term disease control. * To determine which ultrasound parameters and blood biomarkers can distinguish active from inactive disease during treatment. * To evaluate whether extended vascular ultrasound protocols can improve diagnostic accuracy. The ultimate goal is to establish safe, practical tools for improved diagnosis and follow-up in patients with GCA.

The purpose of the study is to recruit as many patients as possible presenting with sacroiliitis or authentic axial spondylarthritis and giant cell arteritis. The investigators will also be interested in the association of spondylarthritis and polymyalgia rheumatica given the continuum between these two pathologies. The aim is to investigate whether there is an association between giant cell arteritis and spondylarthritis or polymyalgia rheumatica and spondylarthritis.

Participants will be followed as part of the usual management of their disease. No modifications will be made (no additional visits, examinations, or questionnaires). The safety and well-being of participants will therefore remain unchanged. The participant will be informed about the study during one of their routine care visits. The information will be provided by the investigator, and the participant's non-opposition to participation in the study will be obtained. The participant will continue to be followed as part of their usual care. Data will then be collected from the participant's medical record (including medical reports, original laboratory test results, imaging reports and medical examinations, and nursing records) for the period of participation in the research, solely for the purpose of meeting the objectives of the research. The data collected will consist of information from the patient's medical record as part of their routine follow-up and will be strictly necessary to address the primary and secondary objectives of the study. The following data will be collected: demographic data (age, sex, weight, height); clinical data (medical history, diagnosed condition, disease activity), treatments, biological data, imaging data, and adverse events. No genetic data will be collected as part of the study. There will be no transfer of data abroad, and no additional questionnaires, examinations, or visits will be added by the research.

Large vessel vasculitis (LVV) is a disease that causes damage to blood vessels. This damage to blood vessels can increase the risk of patients with LVV developing cardiovascular disease, including heart attacks and strokes. A chemical produced in the body called endothelin may contribute to this increase in cardiovascular disease risk by causing the vessels to stiffen and blood pressure to increase. It has previously been shown that by blocking the effects of endothelin, vessel stiffness and blood pressure improve. Bosentan is a tablet that blocks the effects of endothelin. Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor that has been shown to improve blood vessel function and stiffness in patients with diabetes. The investigators plan to assess blood vessel function in those with LVV and participants without LVV. Participants with LVV will be given Bosentan and Dapagliflozin for 6 weeks, followed by Dapagliflozin for 4 weeks, to evaluate their impact on blood vessel function.

Cortisol, a glucocorticoid (GC) hormone secreted from the adrenal glands, is essential for survival. Cortisol also possesses anti-inflammatory actions and GC formulations (prednisolone) are used to treat many inflammatory diseases and conditions. Indeed, three percent of the Danish population (≈ 180.000 individuals) redeems at least one prescription of synthetic GC per year and at least 20,000 patients annually discontinue GC treatment. Pharmacological GC therapy suppresses endogenous cortisol production and thereby induce relative adrenal insufficiency (GIA). The risk of GIA as determined by the adrenal corticotrophic hormone (ACTH) stimulation test has previously been reported to ≈ 25 %, but testing after GC treatment is not routinely performed. Indeed, new evidence suggest that the risk of GIA after planned cessation of prednisolone treatment for polymyalgia rheumatic (PMR) or giant cell arteritis (GCA) is substantially lower, probably 2%. The reason for this discrepancy is undoubtedly selection bias in the previous publications and the use of inaccurate cortisol assays. At the same time, however, it was observed that 25% exhibited pronounced symptoms of adrenal insufficiency based on a questionnaire specific for detecting symptoms of adrenal insufficiency, the so-called AddiQoL-30. Concomitantly, the basal cortisol levels in the same group were significantly lower as compared to the group, who exhibited milder or no symptoms attributable to adrenal insufficiency. This observation aligns with the clinical experience that PMR/GCA patients often complain of fatigue after planned cessation of prednisolone treatment. This often occurs in the absence of objective symptoms or signs of residual PMR/GCA disease activity. The scenario has been designated as "the steroid withdrawal syndrome". This may represent a state of relative adrenal insufficiency prompted by long term, high dose prednisolone treatment. The proper way to tackle this clinical conundrum is to perform a proper randomized trial, which so far has not been conducted. Therefore, investigators of this study will perform the first placebo-controlled randomised controlled trial (RCT) in patients with PMR and GCA after planned cessation of GC treatment. Investigators argue that neither watchful waiting nor routine hydrocortisone replacement are infallible. The study will be the first evidence-based guidance and aid to GIA patients and thus meet an important need for many thousand patients.

The purpose of this study is to evaluate whether the measure of the optic nerve sheath is a reliable diagnostic marker for giant cell arteritis

Polymyalgia rheumatica (PMR) is a rheumatologic condition occurring in patients \> 50 years old, characterized by inflammatory pain of the scapular (shoulder) and pelvic (hip) girdles. PMR is most often isolated but can be associated with giant cell arteritis (GCA), a large vessels vasculitis, in 16 to 21% of case. The main features of GCA are headaches, jaw claudication, visual disturbances, abnormal temporal artery, scalp tenderness associated to elevated CRP and/or ESR. However, GCA could be asymptomatic in particular in case of isolated involvement of large vessels (subclinical GCA). GCA requires high doses of glucocorticoids, compared to isolated PMR, to avoid complications resulting from vascular remodeling (stroke, blindness). Ruling out GCA in PMR patients relies on the performance of some complementary exams that explore cranial vessels as color doppler ultrasound and/or temporal artery biopsy and large vessels that relies on PET/FDG or angio CT scan. The aim of this study is to identifie serum biomarkers that could rule out or identifies GCA in patients with PMR features. Ultimately, if biomarkers are identified, this could allow to select PMR patients in whom complementary exams are needed or not. For this study, investigators chose to explore thrombomodulin. Thrombomodulin is a protein that is increased in the circulating blood during vascular inflammation, and therefore seems to be a good candidate for distinguish isolated PMR from PMR associated with GCA.

The CARe RAiSE project represents a pioneering translational initiative aimed at advancing precision medicine in the treatment of autoimmune rheumatic diseases. The primary objective is the development and implementation of an innovative cell-based ex vivo assay that enables individualized prediction of therapeutic response to disease-modifying antirheumatic drugs (DMARDs). By identifying the most effective treatment option for each patient, this approach seeks to enhance therapeutic efficacy, reduce time to clinical response, and minimize healthcare costs. Despite the availability of numerous DMARDs, clinical decision-making remains largely empirical due to considerable interindividual variability in treatment response. This frequently results in a prolonged trial-and-error process, placing a significant burden on patients and the healthcare system. CARe RAiSE aims to overcome this limitation by providing a functional diagnostic tool that can predict a patient's immunological response to specific DMARDs prior to treatment initiation. The assay is based on peripheral blood mononuclear cells (PBMCs) obtained from individual patients, enabling a physiologically relevant assessment of immune responsiveness to targeted therapies. Combining high-content imaging with homogeneous well-based cytokine and inflammasome activity assays, the platform allows for a detailed single-cell analysis of inflammatory pathways. These data are used to generate predictive signatures of treatment response, thereby facilitating a mechanistically informed and personalized therapeutic strategy. Through this approach, CARe RAiSE introduces a scientifically grounded, efficient, and patient-specific method for DMARD selection, with the potential to substantially improve patient outcomes and reduce the socioeconomic impact of autoimmune rheumatic diseases.

Giant cell arteritis is a vasculitis, i.e. inflammation of the artery walls, which generally affects people over the age of 50. Diagnosis can be long and difficult, as the clinical signs are not specific (headache, pain in the jaw, scalp, shoulders and/or pelvis, abdominal pain, weight loss, etc.), but it must be made quickly, given the risk of complications. The reference method for diagnosis was initially based on clinical suspicion and analysis of a "piece of temporal artery" (biopsy) performed in the operating theatre under local anaesthetic. Since the mid-1990s, improvements in ultrasound techniques have made it possible to identify a sign, known as a halo, on the temporal arteries that is typical of patients with Giant Cell Arteritis. A prospective multicenter study published in 2024 demonstrated that, in patients with a clinical suspicion of Giant Cell Arteritis, if a halo was found on both temporal arteries by ultrasound, there was no need for a biopsy. This study is at the origin of a change in practices in the diagnosis and care of patients suffering from this disabling disease. To facilitate early diagnosis, a fast-track pathway has been set up. The aim is to make a rapid diagnosis, thereby reducing the risk of after-effects, shortening the length of hospital stays, considering outpatient treatment and limiting the number of biopsies. The investigators propose to evaluate the performance of this fast-track pathway.

The AYLo study (AutoimmunitY and Loss of y - Investigating the Role of Hematopoietic Mutations and Mosaic Mutation in the Y Chromosome in Autoimmune Rheumatologic Diseases) aims to systematically investigate hematopoietic mutations, such as hematopoietic (mosaic) loss of the Y chromosome (mLOY), focusing on their underlying causes, pathophysiological significance, patterns of manifestation, and impact on disease progression in autoimmune, rheumatologic disorders. This research seeks to bridge existing knowledge gaps by exploring how such mutations influence immune homeostasis, cellular function, and susceptibility to inflammation-driven pathologies. Through the integration of advanced immunological profiling, the study aspires to uncover key mechanisms that drive the initiation, progression, and complications of autoimmune rheumatic diseases. These analyses will combine single nucleotide polymorphisms (SNP) arrays, multiplex assays, transcriptomics, and flow cytometry staining of peripheral blood mononuclear cells to delineate the interplay between hematopoietic mutations and immune dysregulation. A further objective is the development of a multimodal framework for disease-specific characterization, enabling precise mapping of mutation-driven phenotypes across diverse autoimmune conditions. This framework will incorporate clinical, molecular, and imaging data. Additionally, the AYLo study aims to explore the potential role of mLOY and other hematopoietic mutations as biomarkers for disease stratification, prognosis, and therapeutic response. The findings may open avenues for personalized treatment approaches, leveraging the molecular insights to inform targeted interventions and improve patient outcomes in autoimmune rheumatic disorders. By integrating translational and basic science approaches, this study has the potential to redefine current paradigms in autoimmune disease research and therapy.

This prospective study is to explore different predictive factors for response to steroid treatment in patients with PMR and/or GCA. It evaluates the association of endogenous GC suppression (plasma and urinary cortisol and cortisone) to the responsiveness of PMR/GCA to GCs.

Ankylosing spondylitis, radiographically negative axial spondyloarthritis, psoriatic arthritis, polymyalgia rheumatica, Takayasu arteritis, giant cell arteritis, non-ocular Behcet's disease, and enthesitis-related arthritis are common diseases in rheumatology. Traditional anti-rheumatic drugs are less effective and have greater side effects than biological agents. At present, there has been no large-scale registration study on rheumatic autoimmune diseases such as spondyloarthritis in China. However, data such as patient characteristics, medication patterns, and patient outcome reports of different rheumatology diseases can often serve as a reference for rheumatology clinicians to reasonably select treatment methods for different patients. Therefore, a large-scale registration study is needed to fill the gap in multi-disease registration studies in rheumatology departments in China.

This is a french multicenter observational study assessing safety and efficacy of biosimilar of Tocilizumab in Giant Cell Arteritis (GCA) with active aortitis, including 14 reference centers from the Groupe d'Etude Français des vascularites des gros vaisseaux (GEFA). Giant Cell Arteritis (GCA), formerly known as temporal arteritis, is the most common form of systemic vasculitis in patients aged ≥ 50 years. GCA is defined by granulomatous arteritis that affects large#sized and medium#sized blood vessels with a predisposition to affect the cranial arteries. Aortitis accounted for more than 50% of GCA patients with the new imaging techniques. Aortitis is typically diagnosed using imaging tests such as magnetic resonance imaging (MRI) or Computed Tomography (CT) scans. Aortitis is an inflammation of the aorta, leading to a range of symptoms such as fever, weight loss, fatigue, and chest pain. In severe cases, aortic aneurysms or aortic dissection can occur, which can be life-threatening. Multiple reports have demonstrated the presence of abnormal pro-inflammatory cytokine production in large-vessel vasculitis patients, particularly those with GCA, including interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor-α (TNF-α), and interferon-γ, by T lymphocytes and macrophages. IL-6 has been implicated as a crucial cytokine in the pathogenesis of aortitis and targeting its signaling has shown promising results in treating the condition. IL-6 inhibitors such as tocilizumab have been found to effectively reduce disease activity and improve clinical outcomes in GCA patients. The GIACTA study (GiAnt cell arteritis roActemra (tocilizumab) study) was a randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of tocilizumab in the treatment of GCA. The study included 251 patients with newly diagnosed or relapsing GCA and found that treatment with tocilizumab significantly increased the proportion of patients who achieved sustained remission from GCA at 52 weeks, compared to placebo. Additionally, tocilizumab was associated with a lower incidence of disease flares and a reduced need for glucocorticoid therapy. Following the positive results of the GIACTA study, tocilizumab was approved for the treatment of GCA in adults with active disease, including aortitis, who have not responded to glucocorticoids, or for whom glucocorticoid therapy is not appropriate, by regulatory agencies around the world, including the US Food and Drug Administration and the European Medicines Agency. However, the efficacy of IL-6 inhibitors on aorta inflammation as assessed by modern and powerful imaging techniques has never been specifically studied in GCA. This observational study will provide important informations on the impact of Tyenne® (tocilizumab) associated with short term low dose steroids on clinical manifestations and vessel inflammation and damage in aortitis of GCA.