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Research and training

STRATA-FIT

The initiative outlined by the STRATA-FIT consortium is truly promising and addresses a critical gap in rheumatoid arthritis (RA) management. Developing computational models to identify and stratify Difficult-to-Treat (D2T) RA patients into clinically relevant phenotypes using real-world clinical data is a significant step towards personalized treatment strategies.

By incorporating biomarkers of inflammation and leveraging computational models, the consortium aims to not only improve the management of D2T RA but also potentially prevent its development in early RA patients. This proactive approach could significantly enhance patient outcomes and reduce the burden of RA on both individuals and society.

The establishment of a European Learning Healthcare System, utilizing privacy-proof federated learning infrastructure, underscores a commitment to patient privacy while harnessing the collective expertise and data across institutions. This collaborative effort holds great promise for advancing the field of rheumatology and ultimately improving the lives of patients with RA.

Squeeze

Squeeze is a European Union funded multinational project that is running over five years. Squeeze is aiming to utilise current available DMARDs for patients with rheumatoid arthritis in a more efficient way leading to better responses and higher quality of life. Please find more information under the collaborations section and the link to the SQUEEZE homepage.

Functional Drug monitoring

One of the main goals in managing RA is to help patients achieve remission. Remission leads to higher chances of radiographic stability, good function, and quality of life. The safety and tolerance of treatment are just as important as its effectiveness. It is common to switch treatments due to safety concerns. Some patients still face daily life challenges even after reaching their target outcome. Nowadays, DMARDs are commonly used following treatment guidelines for RA. These approaches have improved treatment for RA patients. However, personalized medicine is not yet possible at treatment initiation. Currently, there are no markers to assess how well DMARDs work for immunomodulation.

TTV is a DNA circle with genetic variety, discovered in 1997 in patients with unclear hepatitis. It was initially thought to be linked to hepatitis. TTV is common in people with rheumatic diseases and healthy individuals. Most people carry TTV regardless of any disease.

Around 2010, TTV was seen as a marker for the immune system post stem cell transplants. Higher levels were found in various transplant patients (liver, lungs, and kidney). TTV increase varied based on T-cell targeting drugs. TTV levels were linked to immunosuppression and infection risks in organ transplant recipients. Kidney transplant patients with specific TTV levels had stable outcomes. In summary, higher TTV levels increased infection risk while lower levels increased rejection risk. Also in rheumatology preliminary studies have indicated that TTV might be a marker for better treatment response and varies by the utilised drugs. Based on this, we aim to decipher the impact of DMARDs and disease activity on TTV and its potential value in steering treatment decisions.

Models of Care

Another important aspect in management of patients with RA is how recommendations and novel interventions can actually be integrated into the daily living of people with RA and the respective settings of their care provider. To be able to make the best use of research results thorough implementation analyses and plans should be considered. We tackle important questions on how to measure and improve adherence, literacy, e-health interventions and opportunities for integrating novel techniques in workflows.

Patient Research Partners

Patient Research Partners (PRPs) work as valued team members alongside professional researchers, contributing their firsthand knowledge to enhance understanding of the target disease. Their experiential knowledge encompasses insights into a person's condition and how it impacts various aspects of life, such as social interactions and healthcare experiences. Experiential expertise involves the necessary skills and attitudes for successful collaboration in research settings. The incorporation of PRPs into research has developed over the past two decades, becoming a prominent approach, especially for conditions that are chronic and necessitate long-term care. Recognizing the significance of patient-reported outcomes led to the realization that involving patients in the design phase can further enhance the utility of these outcomes. While the rheumatology community acknowledges the progress made in collaborative research, there is a need to establish and implement effective strategies for involving patients in various aspects of research.

We aim to improve the body of evidence on the set-up of PRP communities, integration into research groups, educational opportunities for patients and researchers to enhance collaboration. Collaborative research is lived, but can still always be improved in all our running projects.

Our group was involved in major milestones for collaborative research in rheumatology within EULAR as medical advisor for the EULAR online Course for Patient Research Partners and the update for the EULAR recommendations for the involvement of patient research partners in rheumatology research.

 

Digital Health

E-health, which involves the use of information and communication technologies for health services, covers a wide range of systems and services at the intersection of healthcare and technology. From electronic health records to telemedicine and telemonitoring, e-health presents numerous opportunities for advancing healthcare, improving health education, and upholding patient rights. Addressing the existing disparities in standards of care and access to care across Europe is crucial. The increasing development of initiatives and legislations worldwide reflects the recognition of e-health's potential in promoting healthcare equity. Furthermore, the growing utilization of smartphone apps and social media has led to the development of a new framework in the wide range of e-health. This framework includes the use of mobile devices for gathering both overall and individual health data, offering healthcare details to healthcare providers, researchers, and patients, real-time monitoring of patient vital signs, and providing direct care through mobile telemedicine. Mobile health (mHealth) represents a positive progression in this field, enabling patients to access a variety of applications, online platforms, and other resources with ease. M-health services vary from toll-free emergency helplines or health call centers (accessible in 75% of WHO countries) to programs for treatment adherence and surveillance (found in 48% of WHO countries). Social media stands out as a significant player among these resources, especially considering that in 2020, the global social media users were estimated at 3.8 billion, constituting 49% of the world's population. Given these points, e-health plays a vital role in managing individuals with chronic conditions like rheumatic and musculoskeletal diseases (RMDs). The integration of e-health in rheumatology not only offers patients fresh opportunities to learn about their illness and treatment options and connect with fellow patients but also revolutionizes the notion of life-long care from a disjointed model centered on regular in-person visits to a seamless continuum.

We are currently running different studies together with partners throughout Europe to enhance the usability of digital technologies for better, more precise and feasible options to follow and help our patients. These involves projects around the COTIDIANA and Rheumabuddy4.0 consortia. Within the Medical University, we closely collaborate with the team of Prof. Tanja Stamm from the Institute of Outcomes Research.

Together we are conducting studies identifying the needs of multiple stakeholders to successfully implement e-health technologies, the reliability of e-health patient-generated data and passive sensing technologies.

At-Risk to develop rheumatoid arthritis

The past 15 to 20 years have brought about significant progress in our knowledge to gain a better understanding of the different stages that may come before rheumatoid arthritis. The main goal of this research has been to lay the groundwork for potentially discovering ways in the future to prevent or delay the onset of the disease, even in a preventive context. However, a key step for preventive measures is assessing the risk level to determine the chances of actually getting sick. Being aware of this makes it easier to decide which intervention seems reasonable at any given moment.

Individuals with particular signs suspicious for developing RA are commonly referred to as "at-risk RA". This term is used due to the uncertainty surrounding the actual occurrence of the disease. The European Alliance of Associations for Rheumatology (EULAR) has introduced a definition to tackle this issue, outlining various factors linked to a specific risk. This definition is known as clinically suspected arthralgia (CSA). The likelihood of developing RA rises as more of the 7 criteria mentioned earlier are present. Achieving high sensitivity (> 90%) requires having at least 3 of the 7 parameters, while significant specificity (> 90%) necessitates at least 4 of the 7 parameters. Symptoms like arthralgia, fatigue, and bone degeneration (detected through imaging methods) often precede joint inflammation in individuals later diagnosed with RA. The bone degeneration observed before joint inflammation in RA is most commonly seen in patients with serum autoantibodies, such as ACPA. Similarly, the presence of arthralgia, especially when combined with ACPAs, rheumatoid factor (RF), and latent joint inflammation detected through imaging, significantly increases the likelihood of future RA. Criteria and characteristics should always be viewed in a broader context. The positive predictive value (PPV) of ACPAs for developing RA in the general population is approximately 8%. This indicates that individuals with a positive ACPA test receive a false positive result 92% of the time. PPV rates of around 30% have been noted in relation to non-specific arthralgia in secondary care, and risks of up to 63% have been reported for CSA. These pre-test risks suggest that accurate predictive values and precise forecasting tools are more probable for individuals specifically chosen based on CSA symptoms than those without symptoms. The presence of these particular traits, such as detectability and reversibility, makes this vulnerable stage of arthralgia a great opportunity to implement strategies for secondary prevention or intervention.

During the past 10 years we have participated in several collaborative studies in the field of at-risk RA. Currently we are running an observational study of CCP positive individuals with arthralgia suspicious for RA, to better understand factors for the development towards the disease.