Psoriasis and psoriatic arthritis: Joining the dots

A major research project recruiting thousands of patients across Ireland and multiple European countries could help spell the end of psoriatic arthritis

It is estimated that 3 per cent of the population suffers from psoriasis, with an estimated 6.4 million people across Europe being affected. Psoriasis is a condition that causes flaky, itchy, and inflamed patches of skin. It can affect different parts of the body; for example, the back of the arms at the elbow or the scalp. Depending on its severity, it can be a very debilitating condition.

One-in-three people with skin psoriasis will develop psoriatic arthritis (PsA). PsA symptoms include joint pain, stiffness and general fatigue. This form of arthritis may be quite severe and debilitating, leading to rapid degeneration of bone and tissue, typically affecting the joints of hands and feet. As inflammatory auto-immune diseases, psoriasis and PsA also increase the risk for further comorbidities such as cardiovascular diseases, while at the same time affecting mental health with higher rates of depression among individuals affected. The diagnosis and management of the arthritis can present a number of challenges for both the person with the condition and for their healthcare providers. Therefore, early diagnosis and finding the right treatment for the PsA patient is of utmost importance.

The HIPPOCRATES consortium

The HIPPOCRATES consortium is a very ambitious project, involving 27 partner organisations (including universities and industry partners) in 11 countries, with the aligned ambition of addressing the key challenges in early identifi- cation and management of PsA. The HIPPOCRATES project is a five-year project, starting in 2021, which received €23.5 million funding from the Innovative Medicines Initiative (IMI) public-private partnership.

The ground-work for the HIPPOCRATES project was laid during the Covid-19 lockdown in 2020, where the University College Dublin (UCD) team, under Profs Stephen Penning- ton and Oliver FitzGerald, approached colleagues in the rheumatology and dermatology field, made connections with organisations such as GRAPPA, HUPO, EULAR, and EUROPSO, and contacted small- and medium-sized enterprises such as Atturos, Trajan, and Oxford Biodynamics Limited, to initiate the discussion about the need to expand research on PsA. The consortium grew quickly into a community of likeminded individuals who created a structured plan to make an impact on people living with psoriasis and PsA. When a call for grant proposals was issued by the IMI in early 2020, the consortium, now called HIPPOCRATES, submitted a two-stage proposal, which was successful. In the second stage, the consortium engaged with the pharmaceutical companies who were supporting the IMI grant call. The HIPPOCRATES project began in mid-2021.

The patient’s perspective – a key element of HIPPOCRATES

HIPPOCRATES established close ties with individual patients and patient research partners (PRPs), who help to keep the patient’s perspective and opinion a focus of this project. It is notable that from the outset, patient representatives have been involved in planning the grant application, and now that the project is running, they are actively involved at every level. For example, PRPs are involved in every work package, supporting the research design, protocol development, ethical procedures, recruitment strategies, outcome selection, interpretation, and dissemination of study findings.

HIPPOCRATES is structured into eight work packages, which focus on different goals (see Figure 1). These include the identification of specific PsA disease markers which might aid early diagnosis, the prediction of which person with psoriasis will develop PsA, the monitoring and prevention of PsA disease progression, and the identification of personalised treatment options – finding what medication works best for which person. To facilitate this work- plan, the HIPPOCRATES consortium partners are sharing data and samples from previously-conducted studies on psoriasis and PsA populations for extensive omics-based analysis and to establish and validate robust biomarkers across datasets.

“If we could identify which person with skin psoriasis is likely to develop PsA , then we could quite possibly prevent it,” said Prof FitzGerald.

Since it began in 2021, the HIPPOCRATES consortium has held an in-person steering committee meeting and two in-person annual HIPPOCRATES plenary meetings. These meetings have been an opportunity to discuss key points and milestones and foresee challenges for the coming year. Additionally, the meetings have been an excellent opportunity to get to know each other during networking coffee events. The in-person meetings concluded with the HIPPO award ceremony, in which a plush and cuddly hippopotamus is given to individuals who have made outstanding contributions to the project – 16 so far. In a proud moment at a meeting of GRAPPA in 2023, the patient representatives gave Profs Fitzgerald and Pennington a ‘patient HIPPO’ to acknowledge their efforts.

The challenges of working together in such a big consortium are to find the collaborators to drive this project ambitiously forward in different countries, and to keep monitoring milestones every step of the way, since all work packages are progressing in parallel. It is also important to identify additional funding to be able to continue the work after the current envisioned completion of the HIPPO- CRATES project in 2026.

HPOS – HIPPOCRATES Prospective Observational Study

As part of Work Package 2 the HIPPOCRATES partners have established a new online study, the HIPPOCRATES Prospective Observational Study (HPOS). HPOS aims to monitor the development and progression of PsA in a population with psoriasis, and hopes to find ways to prevent the development of PsA in the future. Participants who are over 18 years of age and diagnosed with psoriasis, but not with PsA, will be monitored for three years via six-monthly questionnaires to evaluate their risks for PsA development. Participants who are developing symptoms of PsA are informed about their risks and receive a recommendation to seek a medical assessment with their dermatologist or rheumatologist. Furthermore, those participants developing PsA symptoms will be asked to provide a remotely-collected finger-prick blood sample, which will be shipped to UCD for further analysis of biomarkers to establish their ability to predict PsA in people with skin psoriasis.

So far HPOS has launched in the UK and in Ireland, with nearly 2,300 participants being enrolled in the study. HPOS plans to launch in France, Italy, Spain, Denmark, Germany, Belgium, the Netherlands, Sweden, Portugal, and Greece in 2024. The aim of each country is to recruit 2,000 participants to reach a total number of 25,000 participants across Europe.

“The opportunity to recruit thousands of people with psoriasis across Ireland, the UK, and the rest of Europe is very exciting,” commented Prof Pennington.

Prof FitzGerald said that “individuals who have psoriatic disease have been involved in every aspect of HPOS including study design, promotion, self-recruitment, and con- sent”, and Prof Pennington added that it is “a privilege to be part of such a ground-breaking study”.

In a nutshell

In simpler terms, HIPPOCRATES is attempting to answer the following questions for psoriasis patients:

• What markers can we find, which ensure an early diagnosis of PsA?
• Which person with skin psoriasis is at risk of developing PsA?
• How can we prevent PsA joint damage from occurring? fWhat treatment options work best for the individual with PsA?

The HIPPOCRATES project aims to lay the groundwork for the development of a diagnostic tool for early PsA detection in the form of, for example, a rapid blood test or scan, as part of Work Package 7. The project could lead to the prevention of PsA development, if biomarkers of preliminary symptoms are detected and preventative measures are found for the individual person with psoriatic disease.

Overall, this project will pave the way for an improved understanding of psoriatic disease, characterising its features thoroughly, finding ways to enable early diagnosis, and, importantly, finding novel preventative strategies.

The HIPPOCRATES work packages are making good progress, with data and samples being shared across the different institutes and sites for analysis. Publications are being drafted as we speak and, hopefully, the findings of HIPPOCRATES will soon lead to improvements in psoriasis patients’ lives.

For people with skin psoriasis, but not a diagnosis of PsA, who are aged 18 years or more, who would like to get involved in HPOS, they can find out more and sign up to the study at https://hpos.study/.

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 101007757. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

Authors: Teresa Grohmann (PHD), Postdoctoral Research Fellow;1 Prof Stephen Pennington, Full Professor of Proteomics;1 and Prof Oliver Fitzgerald, Clinical Full Professor1 1 HPOS Study, School of Medicine, University College Dublin