exploRA: a new state-of-the-art approach to manage your rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the joints causing articular stiffness, pain and swelling. It is a systemic autoimmune disease that attacks and destroys the synovial membrane, the bones and the tissues, deeply affecting both physical and mental quality of life. In fact, one year after diagnosis, patients with rheumatoid arthritis are 60% more likely to have a heart attack and the risk of falling into depression increase. 1% of the general population suffers from RA and according to the Italian Society of Rheumatology there are 400,000 patients on our territory.

At present, the treatment of rheumatoid arthritis is based on the use of immunosuppressants such as methotrexate or leflunomide (cs-DMARD), the use of corticosteroids, and NSAIDs to reduce pain. Biotechnological drugs (b-DMARD) have been recently used. These are drugs targeted on specific targets responsible for the inflammatory process, which are usually used after failure of treatment with traditional drugs.

This “trial and error” procedure leads to a slowdown in the early identification of the appropriate treatment for the patient, who in 50% of cases stops the first treatment. This is due to the fact that the same care protocol is applied to all patients and the genetic heritage of the specific person is not taken into account. This procedure leads the subject to visit several doctors and try numerous drugs before finding the right one.

A solution to this problem is personalised medicine: science, data and innovative technologies make it possible to obtain better diagnosis and follow-up considering the biological profile of the patient. In the field of rheumatoid arthritis transcriptomics, the technology that allows to analyse the RNA profile of a particular tissue, organ or cell, is useful. In contrast to DNA (which remains stable), RNA is dynamic, and allows the information on that specific tissue to be monitored over time. The inflammatory process of rheumatoid arthritis is characterised by the malfunctioning of specific genes, which can be detected by the RNA analysis of synovial tissue.

The exploRA test is the first transcriptomic test that helps patients with rheumatoid arthritis to learn more about their disease from the analysis of their genes. By analysing the genetic profile, the altered genes responsible for the inflammation are identified, so that it is possible to understand in advance which drugs will have a positive impact in regulating the malfunction. exploRA uses the BULK-RNA sequencing technique to analyse synovial tissue and blood RNA, and provide relevant information to help the doctor make more conscious choices. Synovial tissue is harvested using a medical procedure called echo-guided synovial needle biopsy performed with a TRU CUT device under local anaesthesia.

The test is composed of three elements: overview, drug action, cellular environment.

The overview provides an overview of altered genes, the genes that are too much or too little expressed compared to normal levels. This generates biological imbalances that lead to inflammation. With exploRA it is possible to detect exactly how many and which genetic components are sending the wrong information to the cells and thus give rise to inflammation.

The action of the drugs can be predicted in advance from the patient’s genetic profile. On the basis of clusters derived from transcriptomy, it is possible to identify drugs that have a positive effect on the mechanisms of genetic regulation and the level of disease activity (DAS). In this way, the physical and psychological stress of a non-working and constantly evolving therapy is relieved.

The cellular environment is reconstructed thanks to iCareX algorithms. These algorithms make it possible to determine which cells produce the altered genes, allowing better characterisation of the tissue composition and even more accurate definition of inflammation.

The detailed exploRA test report is available to both physician and patient via the iTwin digital platform. This allows, on the patient’s side, to learn more about his or her disease and provide feedback on treatment; on the doctor’s side, to have cues to provide the best treatment, to monitor progress and to have the entire medical history available. iTwin also allows to enter the results of further examinations, building an even more complete framework. With iTwin you can view all genetic, pharmacogenetics report and cellular environment in the form of graphs and tables. There is also the possibility to monitor your rheumatoid arthritis with the mobile app.

Thanks to the study of research over the last 20 years, iCareX provides a dynamic platform with personalised data for each patient and relevant information to actively and consciously learn about their disease. In the iTwin Overview you can see at a glance the genes expressed and get an immediate idea of those that are up or down regulated, together with the biological processes in which they are involved. In addition, there is a table showing all the genes expressed and a position indicator allows you to see the expression status of the gene (more or less high) compared to the line indicating normal values. In this way the patient and the doctor can immediately understand how many and which genes are altered. Going into detail, it is possible to observe the cellular composition of the sample and therefore know the percentage presence of certain cells; clicking in each cell one can see all the genes that make it up and their expression.

The section dedicated to pharmaco-transcriptomics is crucial: the graph shows how many genes the drug will have a positive or negative impact on DAS (the disease activity score). Specifically, it can be observed on which genes the drug will act positively or will not have an improvement in DAS. This aspect is essential to know the disease and to provide support for the doctor and the patient.

All processes governing iTwin are developed to protect the privacy of the patient’s health data.

exploRA is a state-of-the-art technology that meets patients and helps them learn about their rheumatoid arthritis. Through the data driven approach it allows to take the first steps towards precision medicine, not standardized but personalized, which focuses on the patient and his singularity.









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