Title: Predicting the development of psoriatic arthritis in people with psoriasis and optimising first line treatment options for people newly diagnosed with psoriatic arthritis: a UK based cohort study.
Funder: Department of Health and Social Care

Abstract: Background Up to thirty percent of people with psoriasis will develop psoriatic arthritis (PsA). Detection of people with psoriasis who are at increased risk for developing PsA is essential to aid early diagnosis and treatment and prevent irreversible joint damage. To date, no validated prediction tool has been created to identify people with psoriasis at risk of developing PsA. Moreover, people with PsA are more likely to have other co-morbidities. The first line treatments used in people with PsA may cause or worsen underlying co-morbidities. The safety of the use of them in people with PsA and other co-morbidities is not fully understood and current guidance on this is limited. Aims To predict the risk of developing PsA in people with psoriasis (Objective 1). To assess the safety of the first-line treatments used in people with co-morbidities newly diagnosed with PsA (Objectives 2, 3, 4, 5).Objectives 1. To develop and externally validate a model that can predict the development of PsA in people with psoriasis. 2. To calculate the prevalence and incidence of co-morbidities before, and the risk of developing the same co-morbidities (with adjustment for age) after the diagnosis of PsA. 3. To identify the clusters of co-morbidities that exist in people with newly diagnosed PsA before they start first-line treatment for PsA. 4. To characterize first-line drug use in people with PsA in the different co-morbidity clusters identified in objective 3. 5. To assess the comparative safety of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) used in people with PsA and how co-morbidities interact with adverse drug reactions of special interest. Methods I will perform a population-based retrospective cohort study using routinely collected NHS primary healthcare data from two UK databases (Clinical Practice Research Datalink (CPRD) GOLD and AURUM). For international validation of the prediction model I will use routinely collected primary healthcare databases from Spain (Information System for the Development of Research in Primary Care) and the Netherlands (Integrated Primary Care Information). The work in this fellowship will be embedded within the HIPPOCRATES consortium, a funded Innovative Medicine Initiative, including 26 partners from 21 institutions across Europe; this gives me free access to all the required databases, providing significant added value to this proposal. Anticipated impact The prediction tool will be used by both NHS patients and clinicians (tailored to each), to identify people with psoriasis who are at increased risk of developing PsA. The results from the drug safety analysis will inform national/ international treatment recommendations for managing people with co-morbidities newly diagnosed with PsA. Dissemination The results will be published in relevant peer-reviewed, open-access journals. Findings will be presented at national/ international conferences. My positions within key research organisations will also allow me to widely disseminate my outputs to relevant bodies (e.g., Group for Research and Assessment of Psoriasis and Psoriatic Arthritis). Plain English summaries will be co-developed with my patient research partners and shared with patient charities and included on the university websites, and social media platforms to maximise public engagement internationally.

Lay abstract: Background Psoriatic arthritis is a type of arthritis that affects around 150,000 people in the UK, and millions worldwide. It has a huge impact on the lives of people living with it and costs the NHS 360 million in direct healthcare costs and the wider economy >1.2 billion in indirect costs each year. Around 1 in 3 people who have the skin condition called psoriasis (which causes thick patches of skin that are red, crusty, itchy, and flaky) will develop psoriatic arthritis. People with psoriatic arthritis are often diagnosed late and this can lead to irreversible joint damage and long-term disabilities. Detecting people with psoriasis who are more likely to develop psoriatic arthritis is essential to help with early diagnosis and treatment and prevent long-term damage. However, we do not currently know or have a way of assessing which people with psoriasis are more likely to develop psoriatic arthritis. In addition, people with psoriatic arthritis are more likely to also have other medical problems such as heart disease and liver disease. The treatments we use for people with psoriatic arthritis have side-effects that could cause or worsen their other medical problems. However, we do not currently fully understand how these side-effects impact people with psoriatic arthritis who have other medical problems. Aims To create a tool that can be used by both NHS doctors and patients (tailored to each) to predict which people with psoriasis are more likely to develop psoriatic arthritis. To assess the side-effects of the treatments used for people with psoriatic arthritis who have other medical problems.Methods I will use information about adults with psoriasis and psoriatic arthritis that is routinely collected as part of their visits to their GP in the UK. Firstly, I will use the work I will do before starting this fellowship where I will identify the factors (such as how bad their psoriasis is, blood test results, whether they smoke) linked to the development of psoriatic arthritis in people with psoriasis. Using this information, I will create a tool that can be used to predict which people with psoriasis are more likely to develop psoriatic arthritis. Secondly, I will look at what medical problems people newly diagnosed with psoriatic arthritis have. I will then look at what drugs were first used to treat their psoriatic arthritis and if they developed any side effects from this. That is whether they developed any new medical conditions or made any underlying medical conditions worse. Patient and public involvement (PPI) British PsA Consortium (BritPACT), which includes a network of thirty patient research partners, helped define the specific aims for this proposal. This was based on the results of a survey that was answered by psoriasis/ psoriatic arthritis patients, carers, and doctors to identify questions they want researchers to address. From this group, I recruited eight people for a project-specific PPI group. They have helped to design my research to ensure it will be of most benefit to patients. For example, following their feedback I will now create a prediction tool that can also be used by patients (not just doctors). Going forward, I will meet with them twice a year to review research progress and seek feedback. Sharing results I will publish the findings in scientific journals and speak about it at national conferences, such as the British Society of Rheumatology. I will work with my PPI group to develop summaries of the research findings for circulation to national societies and charities for people with psoriasis and psoriatic arthritis. I will also use social media and university websites to reach the wider public.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: SKIN;INFLAMMATORY AND IMMUNE SYSTEM