Psoriatic arthritis (PsA) is a chronic, immune-mediated disease that affects structures of the musculoskeletal system such as joints as well as the skin, and is estimated to affect 5–10 million people in the EU. PsA manifests itself through symptoms such as pain, joint stiffness, and fatigue, and can therefore impair many aspects of daily life, including function and productivity. Increasingly, PsA is known to be associated with additional comorbidities, particularly those affecting mental health, such as depression, as well as those that promote the development of atherosclerosis and thus contribute to an alarming increase in cardiovascular morbidity and mortality. PsA usually develops on the background of established psoriasis and nail psoriasis. Due to the heterogeneity of PsA, diagnosis can be difficult, as there are currently only classification criteria, but no diagnostic criteria or specific laboratory tests available. This often leads to delayed initial diagnosis, which can be associated with disease progression. In addition to the heterogeneity of PsA in terms of clinical presentation, disease course and response to targeted therapies also vary widely among patients. Early targeted therapy, as well as the characterization of patient phenotypes based on a detailed molecular profile including predictive markers, are essential to improve long-term outcomes, prevent functional impairment, and ideally prevent the development of PsA altogether.

Three Fraunhofer institutes of the Fraunhofer Excellence Cluster Immune-Mediated Diseases CIMD (Fraunhofer ITMP, IAIS, and IGD) are involved in the European HIPPOCRATES consortium (Health Initiatives in Psoriasis and PsOriatic arthritis ConsoRTium European States), which was established to identify patients at risk of developing PsA and to develop diagnostic methods as well as personalized treatment approaches. Founded as a transdisciplinary consortium, the project team comprises 26 partner institutions from Belgium, Denmark, Germany, Ireland, Italy, Spain, Sweden, Switzerland, the Netherlands, the United Kingdom, and the United States of America. Led by University College Dublin, the partners contribute a broad range of expertise, including clinical, scientific, data-analytical, and ethical knowledge, as well as experience from the patient perspective and the pharmaceutical industry, to pursue the ambitious goals of the HIPPOCRATES project. The project has a duration of five years and a total budget of EUR 21 million, provided by the Innovative Medicines Initiative (IMI 2), a joint undertaking of the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). Of the total budget, 50% is contributed by EFPIA partners (Novartis [EFPIA Lead], UCB [EFPIA Co-Lead], Pfizer, and BMS) and 50% by the EU.

“We expect that the advances achieved by HIPPOCRATES will lead to significant innovations that improve patients’ quality of life,” says Prof. Oliver FitzGerald, Newman Clinical Research Professor at University College Dublin, Conway Institute for Biomedical and Biomolecular Research, Ireland, and coordinator of the HIPPOCRATES consortium. Co-coordinator Prof. Stephen Pennington, Professor of Proteomics at University College Dublin and also at the Conway Institute, adds: “These advances will include the identification of subpopulations and endotypes, the validation of existing and identification of new biomarkers, improved imaging capabilities, and the development of a sustainable infrastructure for future PsA research.” “HIPPOCRATES holds great promise for powerful new tools to advance both early diagnosis and treatment of patients with PsA. In addition, and to enhance effectiveness, a strong patient focus plays an essential role in HIPPOCRATES, made possible by integrating patient research partners into all work packages of the project,” adds Denis O'Sullivan (patient representative of GRAPPA-EU). “This public–private partnership is a great opportunity to unravel this highly heterogeneous disease and enable the development of novel PsA therapies and treatment strategies, including precision medicine approaches,” adds Dr. Christine Huppertz, Senior Principal Scientist in Autoimmunity, Transplantation, and Inflammation at Novartis and EFPIA Lead of the consortium.

To achieve its goals, the HIPPOCRATES project will establish an integrated database to combine cohorts and datasets from major European PsA studies and will build a Europe-wide library of relevant clinical biosamples. HIPPOCRATES will also initiate a large prospective observational study involving 25,000 psoriasis patients to better characterize the transition from psoriasis to PsA. In addition, the expert team will evaluate and validate biomarkers for early PsA diagnosis, for identifying psoriasis patients at risk of developing PsA, for identifying PsA patients at highest risk of rapid progression of bone damage, and for personalized or stratified treatment strategies. Overall, HIPPOCRATES places particular emphasis on the involvement of patients, clinicians, primary care providers, regulatory authorities, SMEs (ATTUROS Limited, Oxford Biodynamics Limited, and NEOTERYX Limited), and relevant large industry partners to meet the needs of all stakeholders and maximize the project’s impact.

In cooperation with the Department of Rheumatology at Frankfurt University Hospital, Fraunhofer ITMP was involved at an early stage in planning the project’s thematic direction and institutional composition. Together with its Fraunhofer CIMD partner institutes Fraunhofer IAIS and IGD, it will lead two of the seven work packages within HIPPOCRATES, covering the topics “Early Diagnosis of PsA” and “Data Integration and Analysis.” For early detection of PsA, the Fraunhofer team will determine clinical, imaging, and molecular disease characteristics and capture them in a combined context in order to derive algorithms for PsA diagnosis. Data integration and analysis will involve the use of machine learning to model an AI-based risk score for the progression from psoriasis to PsA, as well as a risk score for rapid bone-damaging disease progression and a response score to predict response to specific treatments.

“HIPPOCRATES offers us the opportunity, in cooperation with leading European experts, to gain a deeper understanding of PsA in order to improve the function and quality of life of many affected patients,” says PD Dr. Frank Behrens, Head of Clinical Research at Fraunhofer ITMP and member of the Directorate of Fraunhofer CIMD. “I am confident that our project will identify new markers that enable early detection of PsA, improve treatment response, and possibly even open pathways to disease prevention. With the unique combination of diverse expertise represented in Fraunhofer health research—from medicine and multi-omics to image processing and data sciences—we can make an important contribution.”