Connective Tissue Diseases

Genetic testing (GT) (including targeted panels, exome and genome sequencing) is increasingly being used for patient care as it improves diagnosis and health outcomes. In spite of these benefits, genetic testing is a complex and costly health service. This results in unequal access, increased wait times and inconsistencies in care. The use of e-health tools to support genetic testing delivery can result in a better patient experience and reduced distress associated with waiting for results and empower patients to receive and act on medical results. We have previously developed and tested an interactive, adaptable and patient-centred digital decision support tool (Genetics ADvISER) to be used for genetic testing decision making, and have now developed the Genetics Navigator (GN), a patient-centred e-health navigation platform for end-to-end genetic service delivery. The objective of this study is to evaluate the effectiveness of the GN in an RCT in reducing distress with patients and parents of patients being offered genetic testing. Results of this trial will be used to establish whether the GN is effective to use in practice. If effective, GN could fill a critical clinical care gap and improve health outcomes and service use by reducing counselling burden as well as overuse, underuse and misuse of services. These are concerns policy makers seek to address through the triple aims of health care1. This study represents a significant advance in personalized health by assessing the effectiveness of this novel, comprehensive e-health platform to ultimately improve genetic service delivery, accessibility, patient experiences, and patient outcomes.

Connective tissue disease (CTD), an autoimmune and inflammatory disease, usually accompanied by lung interstitial/alveolar inflammation and fibrosis (so called interstitial lung disease, ILD). The prevalence and mortality rate of CTD-ILD increase in recent several years. Although the use of corticosteroids and strong immunosuppressants can improve ILD in some patients with CTD, progressive lung fibrosis which needs lung transplantation and results in respiratory failure, even with mortality is observed. Currently, stem cell therapy is a breakthrough in the treatment of CTD-ILD, and the effective therapy with stem cells for patients with ILD have been reported.

Connective tissue diseases (CTDs) cover a broad range of systemic rheumatic disorders characterized by abnormal immune activation, chronic inflammatory response, and fibrosis of internal organs. The most prevalent is interstitial lung disease (ILD), a severe pulmonary complication seen in 10 to 50% of CTDs and a major determinant of disability and death. Prevalence and clinical course of CTD-ILDs vary widely and seem to be independent of treatment. Current screening and prognosis prediction strategies based on clinical variables and auto-antibodies are inadequate, and disease biomarkers are lacking. The research project aims to identify biomarkers of ILD involvement in CTD patients by characterizing the proteome and transcriptome of extracellular vesicles (EVs) isolated from serum. This will be integrated with high-resolution computed tomography (HRCT) using artificial intelligence (AI)-based imaging assessment. These novel biomarkers are expected to address some current limitations of standard laboratory biomarkers and conventional HRCT imaging. The investigator will involve a total of 200 CTD patients divided into two equal groups: those with ILD and those without. Serum EVs will be extracted from patient sera and characterized based on proteome and transcriptome content using mass spectrometry analysis and next-generation RNA-sequencing. The investigator will compare CTD patients with and without ILD, and progressive and non-progressive ILD patients according to OMERACT (Outcome Measures in Rheumatology) initiative criteria during a 12-month follow-up. HRCT features analyzed by a commercially available deep learning AI software will also be compared among CTD-ILD patients based on the occurrence of progression during follow-up. An advanced approach combining EVs analysis in serum and AI algorithms of HRCT images, and functional fibrosis assessment in vivo, could enhance our understanding of CTD-ILDs pathogenesis. The proposal aims to investigate for the first time the EVs proteomic and transcriptomic profile in serum of patients with CTDs to identify possible biomarkers of lung involvement. The integration of circulating EVs biomarkers with clinical phenotype and with advanced imaging technologies will provide novel diagnostic algorithms that early identify patients with lung involvement in CTD and patients at risk of pulmonary progression.

The investigators hypothesize that in patients with a new diagnosis of Pulmonary Interstitial Disease (PID), adding capillaroscopy to standard care increases the proportion of patients receiving a diagnosis of PID-Connective Tissue Disease (PID-CTD) within the first three months of follow-up, thereby reducing the time to diagnosis and facilitating the implementation of appropriate treatment as quickly as possible. Therefore, To confirm this hypothesis, it is necessary to know the characteristics of capillaroscopy in patients with a new diagnosis of PID.

The overall study objectives outlined in this study are to derive 129Xe MRI pulmonary vascular biomarker signatures that differentiate common subtypes of PAH and to determine the ability of 129Xe MRI to longitudinally monitor disease progression and response to therapy in PAH, with the aid of additional assessments, such as labs, echocardiography, and six-minute walk distance (6MWD).

Rheumatic diseases are chronic inflammatory conditions that can lead to long-term tissue damage and increased cardiovascular and metabolic risk. Advanced glycation end products (AGEs) are harmful molecules that accumulate in the body over time and are known to promote inflammation and oxidative stress. Increased AGE burden has been implicated in several chronic diseases; however, its role in rheumatic diseases has not been fully clarified. This observational, cross-sectional study aims to evaluate the accumulation of AGEs in patients with various rheumatic diseases compared with healthy individuals. AGE levels will be assessed non-invasively using skin autofluorescence measurements. By comparing AGE burden between patients and healthy controls, this study seeks to improve understanding of the potential role of AGEs in the pathophysiology of rheumatic diseases and to explore their usefulness as a non-invasive biomarker in clinical practice.

This is an open label extension (OLE) study of an ongoing randomized controlled parent clinical studies 218224 (NCT05878717) and 221672 (NCT06572384) which aim to assess the efficacy and safety of belimumab on reducing the decline in lung function in participants with interstitial lung disease associated with diffuse cutaneous systemic sclerosis (dcSSc-ILD) and interstitial lung disease associated with other connective tissue diseases (CTD-ILD), respectively. The OLE study will describe how well tolerated belimumab will be long term, and whether it might continue to slow progression of lung function decline, slow overall disease progression and improve quality of life.

Study for clinical and radiological presentation of patients with connective tissue diseases who complain from pleuropulmonary symptoms

The goal of this clinical trial is to evaluate the efficacy and safety of Telitacicept for the treatment of connective tissue disease-associated thrombocytopenia.

This prospective, open-label, single-center, one-arm clinical trial aims at evaluating the efficacy and safety of avatrombopag in Chinese adult Immune Thrombocytopenia (ITP) patients with autoantibodies fail (due to intolerance or resistance) to eltrombopag or herombopag treatment.

The RMD-mILDer trial is a home monitoring strategy trial aiming to improve management of interstitial lung disease related to rheumatic diseases applying eHealth technology. It is planned as a 2 arm 54 week multi-centre randomised controlled trial to assess outcome of home monitoring with bi-weekly serial forced vital capacity- and patient reported outcome-measurements compared to standard of care with fixed-interval hospital visits in adult patients with rheumatic disease associated interstitial lung diseases.

This study aims to improve the understanding of how genes and the environment can influence and cause pulmonary fibrosis. By identifying the presence of genes and other factors that can put people at risk of developing pulmonary fibrosis, the influence these factors have on the progression of the disease can be studied. Interstitial lung disease (ILD) is the medical term given to a group of lung diseases affecting the same part of the lung, the interstitium, each with similar symptoms. In some of these diseases, inflammation leads to lung scarring, known as fibrosis. Idiopathic Pulmonary Fibrosis (IPF) is one of these diseases; it has a particular pattern on computed tomography (CT) scans. IPF is 'idiopathic' as it is not yet fully understood why it happens. It has a poor prognosis. The average survival time is three to five years after diagnosis. While new antifibrotic drugs offer hope of slowing disease progression, lung transplant is the only cure, and it comes with its significant risks. Although it is not fully understood what causes IPF, it is known that genetic factors significantly increase the risk of developing the disease. Up to a quarter (25%) of people with IPF with a family history appear to have a causative genetic variant. Familial-pulmonary-fibrosis (FPF), the term for people with at least one relative with IPF, may have worse disease when compared to those without a family history. However, this needs more research. Patients with specific genes, telomere-related gene variants, appear to have a greater risk of developing blood disorders from medications given to suppress the body's immune system after a lung transplant. Progressive pulmonary fibrosis is pulmonary fibrosis where there is irreversible worsening of the disease, worsening of lung function, respiratory symptoms and even early death. It is of growing importance regardless of the cause, whether it be idiopathic, familial or secondary to a connective tissue disease. ILD is increasingly recognised as a complication of connective tissue diseases. It is the leading cause of death in people with systemic sclerosis. The new antifibrotic drugs slow the progression of CTD-ILD. People with progressive pulmonary fibrosis who have a greater than 10% drop over one year in a measure of their lung function, called the forced vital capacity, benefit most from antifibrotic therapy. Early identification of people with progressive disease would allow the commencement of treatment quicker. At-home spirometry may be a way of identifying those who are worsening early. This study hypothesises that by improving knowledge of factors that affect disease behaviour and progression and assessing tools for the early identification of progressive disease, such as at-home spirometry and CT scan pattern determination by deep-learning analysis, we can provide 'precision' diagnosis and treatment. It is hoped that this improved understanding will help reduce the clinical risk for people with pulmonary fibrosis and their families. This study aims to recruit 300 patients: 100 with IPF, 100 with FPF, and 100 with CTD ILD. Each participant will be followed for one year. This observational study aims to help answer a number of questions: 1. What genetic variants cause people to develop ILD, and which increase a person's risk of developing ILD are present in the study population? 2. How does pulmonary fibrosis behave in people who have a family history of IPF compared to those who do not and in people with CTD-ILD? 3. Are different types of pulmonary fibrosis more progressive than others i.e. Is pulmonary fibrosis in those with a family history of pulmonary fibrosis more progressive than in those who do not have a family history? 4. Is the disease in those with a genetic variant known to cause ILD worse than in those who don't have a gene? 5. Can at-home spirometry help identify people at risk of progressive disease early? 6. Can deep-learning analysis (AI) be used to find CT scan patterns to predict when pulmonary fibrosis will worsen?

Connective tissue disease (CTD) is a common group of autoimmune diseases, mainly including systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) , and so on. APS is caused by autoimmune disorders that cause recurrent miscarriage, thrombosis, and thrombocytopenia, and often secondary to connective tissue diseases such as SLE. Undifferentiated connective tissue disease (UCTD) is currently considered to be an independent disease in the classification of CTD. And women of childbearing age who suffer UCTD is more common than that in other definite CTDs. Therefore, the impact of the disease flare and the influence of medicine on pregnancy and lactation are important for these patients who may suffer high-risk of abnormal pregnance.

Adult patients with suspected or confirmed Connective Tissue Disease Patients (CTD)With Pulmonary Hypertension(PH)will be recruited. Patients will be approached, consented, have baseline demographics, diagnostics and disease activity measures recorded, and blood taken. The collection of data and biological material will mirror usual clinical practice as far as possible. Subjects will ideally attend further visits at 3, 6 and 12 months to have bloods taken, outcome measures recorded and questionnaires completed.

The RECONNECTIVE Registry is an observational single center study, focused on the subgroup of precapillary pulmonary hypertension related to connective tissue diseases. All patients will have hemodynamic confirmation by right heart catheterization and will be follow-up for at least 5 years from admission. All patients diagnosed with Group I Pulmonary Arterial Hypertension (PAH) associated with Connective Tissue Diseases (CTD) and Group IV Pulmonary Hypertension (PH) with CTD will be included. The purpose of the registry is to learn and understand the clinical outcomes and natural history of the pulmonary arterial hypertension in this subgroup of patients to improve the medical care and treatment.

Comparing percutaneous needle fasciotomy +/- corticosteroid injection for Dupuytren's contracture affecting metacarpophalangeal joints. A clinician-initiated, multicenter, randomized controlled trial.

Despite a number of prospective studies already initiated in the past years, the current epidemiology and course of interstitial lung disease (ILD) and pulmonary hypertension (PH) in patients with connective tissue disease (CTD) is still not well defined, particularly regarding its prevalence, incidence and the management of a broad spectrum of disease presentations. Major challenges include the identification of patients with progressive disease, the appropriate time point of therapeutic intervention and the underlying driver of disease (inflammatory or pro-fibrotic stimulus or both?). To address these issues in Western Austria, a progressive registry of patients with CTD exploring routine clinical and pathophysiological characteristics of ILD and PH will be conducted. This multidisciplinary, prospective and observational registry aims to collect comprehensive clinical data on incidence, prevalence and course of disease regarding all PH and ILD presentations in a real-world setting.