Psoriasis and psoriatic arthritis: Joining the dots

Reference: June 2024 | Issue 6 | Vol 10 | Page 44

Psoriasis and PsA

It is estimated that 3 per cent of the population suffers from psoriasis, with an estimated 6.4 million people across Europe 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, and depending on severity it can be a very debilitating condition.

Prof Oliver FitzGerald and Prof Stephen Pennington, HIPPOCRATES

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 this 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 an 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 identification and management of PsA. HIPPOCRATES is a five-year project which started in 2021 and received €23.5million funding from the Innovative Medicines Initiative public-private partnership.

The groundwork for the HIPPOCRATES project was laid during the Covid-19 lockdown in 2020, when the UCD team, under Profs Stephen Pennington and Oliver FitzGerald, approached colleagues in the rheumatology and dermatology field, made connections with organisations such as the Group for Research and Assessment of Psoriasis and PsA (GRAPPA), the Human Proteome Organisation, the European Alliance of Associations for Rheumatology, and The European Umbrella Organisation for Psoriasis Movements, and contacted small and medium-sized enterprises (SMEs) such as Atturos, Trajan, and Oxford Biodynamics Limited, to discuss the need to promote research into PsA.

The consortium grew quickly into a community of like-minded individuals, who created a structured plan to make a meaningful impact on people living with psoriasis and PsA. When a call for grant proposals was issued by the Innovative Medicines Initiative (IMI) in early 2020, the consortium, now called HIPPOCRATES, successfully submitted a two-stage proposal. 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.

FIGURE 1: HIPPOCRATES plan and work packages. Source: HIPPOCRATES-IMI website

The patients’ 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 each person.

To facilitate this workplan, 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, 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 Prof Fitzgerald and Prof Pennington a ‘patient HIPPO’ to acknowledge their efforts.

The challenges of working in such a large consortium are finding the collaborators to drive the project forward in different countries, while 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 HIPPOCRATES project in 2026.

HPOS – HIPPOCRATES Prospective Observational Study

As part of Work Package 2 (WP-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 1,300 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 consent”, 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?
• What 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 (WP-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; characterise its features thoroughly; find ways to enable early diagnosis; and, importantly, find 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 the lives of psoriasis patients.

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

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