An estimated 3% of the world’s population have psoriasis, with approximately 6.4 million people across Europe affected. Almost one third of people with psoriasis will develop psoriatic arthritis (PsA), a disease that can be severe and debilitating and lead to irreversible degeneration of bone and tissue, typically affecting the joints of hands and feet.
As inflammatory autoimmune diseases, psoriasis and PsA also increase the risk for further comorbidities, such as cardiovascular diseases and obesity, with higher rates of depression among those affected.
Although notable advances have been made in the range of treatment options for PsA, it remains difficult to diagnose. No specific diagnostic criteria or laboratory tests are available, and the disease course and response to treatment can be unpredictable.
Professor Stephen Pennington
Dermatologists need better tools to be able to recognize when they should refer their psoriasis patients to rheumatologists.
Professor Oliver FitzGerald (left) and Professor Stephen Pennington
“Another key unmet need relates to whether we can reliably identify risk factors for which a person with psoriasis will develop PsA. We know that 30% will develop PsA, but we cannot identify which person with psoriasis is at risk,” Professor Oliver FitzGerald of University College Dublin (UCD), an international opinion leader in rheumatology, told Medscape Medical News. A clearer understanding of PsA could lead to development of tools for its early diagnosis and identification of disease prevention strategies, he explained.
Thus, HIPPOCRATES (Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States ) was created. This ambitious research consortium was conceived by FitzGerald and his colleague Stephen Pennington, professor of proteomics at UCD, together with a number of likeminded colleagues in the fields of rheumatology and dermatology and at organizations such as GRAPPA, HUPO, EULAR, and EUROPSO.
The collaboration has brought together world-leading clinicians, researchers, and people living with psoriasis and PsA to address the main challenges in its early identification and management.
HIPPOCRATES received €23.5 million in funding from the EU Innovative Medicines Initiative public-private partnership in 2021 and is now half way through its 5-year plan.
Key Goals
HIPPOCRATES involves 27 partners, including from industry, in 11 countries.
Its four key goals are:
Identifying specific PsA disease markers to develop accurate diagnostic tools;Developing prediction strategies to identify which person with psoriasis will develop PsA;Monitoring and prevention of PsA disease progression to irreversible joint damage; andIdentifying personalized treatment options, so that patients are treated with the right medicines for their specific disease.
Prof Stephen Pennington
“The pharmaceutical companies have come up with a veritable armory of potential treatments, but rheumatologists still don’t know which one to use for a particular patient at a particular time,” Pennington explained to Medscape Medical News. “So the reality is they tend to cycle through treatments until they find one that is effective.” This is not very efficient or desirable for patients, he added.
Multidisciplinary Approach
A key advantage of HIPPOCRATES is that it brings several medical disciplines together. The current approach of clinicians working in silos is a key barrier to earlier diagnosis of PsA.
“The reality is that a patient with psoriasis will see a dermatologist, and dermatologists don’t necessarily have the skills or training to identify the very early stages of psoriatic arthritis, so they will only refer a patient of theirs to a rheumatologist at a very late stage,” said Pennington.
Dermatologists need better tools to be able to recognize when they should refer their psoriasis patients to rheumatologists, so that patients developing PsA are diagnosed and treated earlier, he explained.
GPs will also be an important component of the project because they are the first point of healthcare contact for people with PsA or psoriasis.
“[I]t is about helping GPs diagnose earlier and raise awareness among patients. Historically, there has been a bit of a lag between people having their first symptoms and getting a diagnosis,” explained HIPPOCRATES collaborator Frances Mair, the Norie Miller Professor of General Practice and head of general practice and primary care at the University of Glasgow, United Kingdom.
Mair told Medscape Medical News that diagnosis isn’t always straightforward, and the hope is that the study will identify more specific risk factors that will help GPs flag PsA earlier.
Patient Involvement and Data Sharing
The HIPPOCRATES consortium involves patients in all stages of the project.
“In HIPPOCRATES, patient and public involvement is really a central feature, which is quite unusual at the more experimental side of healthcare and research. In HIPPOCRATES, the patient research partners have a leading role, making a real difference…” said Mair.
To facilitate its goals, the consortium partners are sharing data and samples from previously conducted studies on psoriasis and PsA populations. This will facilitate extensive omics-based analyses to establish and validate robust biomarkers across datasets, using the latest cutting-edge techniques, including machine learning and artificial intelligence.
Professor Frances Mair
Historically, there has been a bit of a lag between people having their first symptoms and getting a diagnosis.
In addition, the HIPPOCRATES Prospective Observational Study (HPOS) was launched last year. This web-based study aims to recruit 25,000 adults (≥ 18 years of age) with skin psoriasis across Europe. They will collect their clinical data every 6 months, including emerging musculoskeletal symptoms. Blood samples will also be collected remotely from a subset of 3000 participants using a finger-prick kit that will be posted to their homes.
HPOS has already commenced recruitment in the UK, Ireland and, most recently, Greece and Portugal, with nearly 2300 participants enrolled to date. HPOS also plans to launch in France, Italy, Spain, Denmark, Germany, Belgium, the Netherlands, and Sweden.
“This ambitious study will give us the statistical power to identify clinical/molecular risk factors for progression from psoriasis to PsA. We anticipate that 675 participants per year will develop PsA in our studied population. Participants will receive regular feedback to help monitor their condition, and we will help them to get the medical care that they need,” said FitzGerald.
Pennington added that the consortium believes it is a “realistic goal” that the resulting molecular risk prediction tools could eventually enable clinicians to intervene to prevent PsA.
From Research to Practice
The HIPPOCRATES projects are making good progress, with several early publications, and further publications being drafted.
“One of the biggest achievements so far has been to assemble this massive resource of patient samples — tens of thousands in total in a single integrated database, which is the foundation of the project,” said Pennington. He explained that it took a significant amount of work to secure the necessary agreements from all 27 partners to share the patient data securely, appropriately, and anonymously within the consortium.
Creating successful biomarkers, algorithms, and other tools is one thing, but disseminating the knowledge learned and rolling out the final agreed guidelines will be just as important as the research work, said Pennington.
Mair, who is responsible for promoting communication, dissemination, and maximizing the impact of the research undertaken by the HIPPOCRATES consortium, said: “We see so often in healthcare that people come with great ideas or tools, yet they don’t become part of everyday practice. Hence, I am working on the implementation side of HIPPOCRATES, to make sure its findings will be embedded and routinely used in practice,” she said.
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