Current Research

Professor Darren Ashcroft, University of Manchester

Psoriasis is a skin condition, resulting from abnormal activity of the immune system (immune-mediated), which causes inflammation of the skin and sometimes joints. It typically causes a rash with itchy, scaly patches on the skin most commonly on the scalp, elbows and knees, Symptoms of psoriasis can change over time and various factors can cause it to flare-up. There are a range of treatments that can improve symptoms and the appearance of skin patches.

Our previous studies have shown psoriasis affects 2-3% of the UK population and it can either begin before the age of 40 years, categorised as early onset psoriasis, or after 40 years of age known as late-onset psoriasis. We have also shown that, although life expectancy for people with psoriasis is improving, it is still lower compared with people without psoriasis.

This study will provide an update to our previous work examining changes in the number of people with psoriasis and life expectancy between 1999 and 2013, covering a much longer time-period. We will examine for the first time how the number of new cases of psoriasis and the total of people with the disease varies by ethnicity (using the CPRD Ethnicity Record). We will also investigate whether the number of psoriasis diagnoses has been impacted by the COVID-19 pandemic, and whether there have been further changes in life expectancy for people with psoriasis. The findings from this study will inform future policy and clinical practice to help people living with psoriasis across the UK.

Dr Esther Burden-Teh, University of Nottingham

“They couldn’t decide whether it was a fungal infection.”

“I had psoriasis for about six and a half months before someone correctly diagnosed me.”

These are the experiences of some children and young people who have psoriasis who took part in the healthtalk.org project. They found the delay in getting a diagnosis to be frustrating and upsetting.

Psoriasis is a skin condition that can cause red, flaky patches on any part of the body including the face, scalp, hands and genitals. Psoriasis can affect adults and children, but psoriasis in children is often confused with other common skin diseases.

Diagnostic criteria can help doctors make a diagnosis. Criteria are a list of skin changes to look for and questions to ask when the patient is seen in clinic. We have developed a version that patients can complete themselves but we don’t know how well it works so we need to test it.

Before starting a large study across several hospitals, it is important to test the design. Therefore, a practice study, called a pilot study, will take place first.

In this practice study, one hundred children and young people will be invited to complete an online diagnostic criteria questionnaire before they have their dermatology appointment. We will compare their responses to the diagnosis given by the doctor. We will also collect information on what makes them more, or less, likely to fill in the questionnaire.

Dr Ella Guest, University of the West of England

Individuals with psoriasis can experience negative attitudes and discrimination from the general population, which can affect their psychological wellbeing (e.g., low mood, anxiety, depression, appearance concerns) and life engagement (e.g., avoidance of activities that draw attention to their skin, romantic relationships) and make it more difficult to manage their condition. Given that most of these challenges stem directly from the attitudes and behaviours of society, which are influenced by the (mis)representation of psoriasis in the media, it is important that charitable organisations have tools to raise awareness of psoriasis, increase knowledge of the condition, and reduce misconceptions towards it. Social media provides a cost-effective and wide-reaching platform for population-level campaigns and is regularly used by the Psoriasis Association; however, the effectiveness of current campaigns has not been assessed. Limited current research suggests including personal stories, educational information, and presenting psoriasis in a positive light may effectively reduce negative attitudes; however, this research is in its infancy. Therefore, further evidence-based research is needed to target negative attitudes towards psoriasis and develop an effective social media campaign intervention. Therefore, in collaboration with adults with psoriasis, this PhD would use a mixed-methods approach to understand experiences of misconceptions and negative attitudes using qualitative interviews and co-produce and evaluate a social media intervention that the Psoriasis Association can use to improve the lives of people with psoriasis by targeting the general public.

Dr Paola Di Meglio, King’s College London

The focus of this proposal is a cellular protein called Aryl Hydrocarbon Receptor (AHR) which responds to dietary, light and microbial stimulation by switching off inflammation in the skin. Importantly, a compound called tapinarof, which works by instructing AHR to switch off inflammation, has been tested as topical medication in people with psoriasis, with good efficacy in around 50% of them. However, it is currently unclear how much AHR there is in the skin of people with psoriasis, what determines the amount, and whether that amount is enough for tapinarof to work as an anti-inflammatory drug. Moreover, some evidence suggests that the amount of AHR in the skin may differin people of different ethnicities. We aim to study the skin of people with and without psoriasis who define their ethnicity according to the UK Census 2021 categories as Asian or White to find out:1)What affects the amount of AHR present in skin cells and whether it varies according toethnicity2)How much AHR is present in their skin3)If the anti-inflammatory effect of tapinarof depends on the amount of AHR present in the skin and whether it varies according to ethnicity. Taken together, these experiments will enhance our understanding of how environmental factors influence psoriasis and treatment in people of different ethnic groups. Moreover, they can provide further opportunities to find novel effective medications or lifestyle intervention to improve the lives of people living with psoriasis.

Dr Zenas Yiu, the University of Manchester

The newer injectable biologic therapies that target interleukin(IL)-17 and 23 are more effective for the treatment of psoriasis compared with the older biologics such as ustekinumab, a IL-12/23blocker, and TNF inhibitors. However, we do not yet know whether these newer treatments lead to more, less, or different types of serious infections in people with psoriasis in the routine clinical setting.

We will perform two studies to investigate this. Our first study will be a review of existing data on this topic, where we will look for all the relevant available evidence comparing the infection risk of IL-17 and IL-23 inhibitors with the older biologics. This will help us understand the strengths and flaws of current research and focus our further research on any gaps in knowledge that exist. If these studies are similar enough, we will combine this data together. We anticipate that the current evidence for the newer biologics will not be as robust.

Our second study will use a large national, well-established, long-term ongoing database of people with psoriasis on biologic therapies. We will test whether people on the newer IL-17 and IL-23inhibitorshave any difference in risk of serious infection, which are those that lead to hospital admission and require intravenous antibiotic treatment, or death, compared with the older biologics, and analyse whether there is any specific type of infection that is more common inpatients on individual biologic therapies.

These studies will provide both psoriasis patients and their doctors with an accurate estimate of the risk of infection while on the newer biologic therapies which will allow them to make well-informed decisions to choose a particular biologic treatment

Dr Zenas Yiu, the University of Manchester

Biologic therapies for psoriasis, which are targeted injection treatments made of manufactured antibodies, are very effective and have transformed the level of success patients with psoriasis can achieve in clearing the skin. These medicines are made using living cell lines and are costly.

Biosimilar is a term used to describe a me-too medicine designed to work in the body in the same way as a biologic medicine already available for use by patients, also called originators. Biosimilars do not need to go through as much testing; makers of biosimilars only need to show there are no major differences between their product and the originator. The costs of biosimilars are usually much lower, offering the NHS cost savings whilst opening opportunities to treat more people in the future.

However, biologics have complex chemical designs, and it is difficult to make a biosimilar that is exactly the same as the originator. Although trials have not shown any difference between biosimilars and originators, we do not yet know whether this is the same in routine clinical practice.

We designed a study using data from the British Association of Dermatologists Biologics and Immunomodulator Register, a large multicentre registry of patients with severe psoriasis based in the UK and the Republic of Ireland, with the objectives to firstly describe the current use of biosimilars for the treatment of psoriasis in the UK; and secondly to generate evidence to show whether biosimilars have the same effectiveness and safety compared to originators under routine clinical practice settings.

Latest results summary

Tumour necrosis factor-alpha inhibitors (TNFi) are injectable treatments that are very effective for the treatment of moderate to severe psoriasis. These medicines were previously costly. Biosimilars, which are treatments that are manufactured so that they are like the original drug (originators),are much cheaper. However, the development process and regulatory pathway of biosimilars are not the same as orginators. Some people are therefore concerned that small differences between biosimilars and originators might have unwanted poorer treatment effects or safety problems when used with patients in clinic.

We performed a systematic review, which is a reproducible, rigorous, and transparent search of the evidence, and found reassuring data to suggest that the treatment effect and safety of biosimilars were no different to originators in people starting these drugs or in people switching to biosimilar drugs. However, we also found that this data was limited because most of the evidence was based on clinical trials, which are carried out over short periods of time in selected groups of patients. We did not find any high-quality studies investigating the use of biosimilars in routine settings.

We conducted a second study looking at the use of biosimilars using data from the British Association of Dermatologists Biologics and Immunomodulator Register (BADBIR), a large multicentre registry of patients with severe psoriasis based in the United Kingdom (UK) and the Republic of Ireland (RoI) and showed that the rate of switching to or starting TNFi biosimilars increased over time and varied across the UK and the RoI. Biosimilar use was found to be more common in male patients or patients with low disease severity.

For the next phase of the project, we will conduct a multi-centre international study in collaboration with research teams across the world to compare the effectiveness and safety of biosimilars to originators for the treatment of psoriasis in real-world settings.

Dr Satveer Mahil, King’s College London

Psoriasis research has delivered powerful drugs (called biologics) which act by influencing the immune system. ‘Remission’ (achieving clear skin with no/low risk of psoriasis recurrence upon stopping therapy) is now achieved more frequently than ever before. However, biologics are still continued lifelong at standard doses. This is costly and burdensome, with regular injections, blood tests, risk of infections and side effects.

We therefore need to identify patients in remission, in whom clear skin could be maintained with less frequent dosing (‘dose tapering’) or by stopping treatment.

1. Identify the immune cell types driving remission.

• We obtained skin biopsies before and after biologic treatment in patients in remission. We will examine individual immune cells present in these samples, using an innovative technique called single-cell sequencing.

2. Confirm that these immune cells are also observed in publicly available studies.

• We will validate the above findings by comparing our individual cell data with results of traditional studies, comprising information from a mixture of cells.

3. Demonstrate the presence of these immune cells in skin and blood collected from a new group of patients receiving biologics.

• We will use experimental techniques to detect the immune cells defined in the previous stages of the study.

The above steps will define the cells driving remission in people receiving biologics. This will identify patients suitable for dose tapering, which may reduce the burden of long-term biologics use and improve outcomes in psoriasis.

Latest results summary

Biologic drugs have revolutionised outcomes in psoriasis, with a growing number of patients achieving clear skin (‘remission’). However, the cells and molecules in skin that drive remission to biologics remain poorly understood.

We used skin samples donated by people with psoriasis to investigate changes in the skin before and during early biologic treatment. We performed a technique called single cell sequencing. By studying individual cells, this powerful technology helped to identify a new cell type that may coordinate the early effects of biologic treatment. We followed up our findings using skin samples from independent donors with psoriasis. We used a method called RNA scope to find out where these cells are located in skin. We found that the new cell type was located near to the upper layer of the skin and decreased in abundance by day 14 of biologic treatment.

Our study has uncovered a new cell type that are ‘early responders’ to biologic drugs, potentially driving early skin clearance in response to treatment. This information may help us to select individuals most likely to respond well to treatments available already, and design better treatments for the future.

Dr Thiviyani Maruthappu, Queen Mary University of London

The APPLE Study (Asking People with Psoriasis about their Lifestyle and Eating) aims to help address one of the commonest questions that people living with psoriasis ask, whether changes in diet may or may not be helpful for their skin. Therefore, developing evidence-based dietary guidance is a key priority. This study aims to address this unmet need by firstly, examining the current diet patterns of people living with psoriasis around the UK, in addition to lifestyle factors such as sleep and exercise. This questionnaire survey will enquire whether people with psoriasis have observed whether particular foods trigger their psoriasis or whether any dietary changes may have helped. Secondly, a small trial will compare two popular evidence-based diets – the Mediterranean diet and “Intermittent Fasting” to observe whether either of these are helpful in improving psoriasis and potentially associated risk factors for heart disease such as high blood pressure and cholesterol levels. By examining the amount of inflammation in the blood as well as the extent of skin involvement at the beginning and end of the study, we will be able to see if either of these diet affects inflammation. The study brings together a unique group of UK experts for the first time, dermatologists, scientists and nutritionists to provide a robust approach in exploring the relationship between diet and psoriasis. The PhD candidate will be a Registered dietician who, at the end of the study, will have developed expertise in the specific needs and challenges faced by people living with psoriasis.

Professor Miriam Wittmann, University of Leeds

We now have a range of medicines available to treat psoriasis. These therapies work in many but not all patients and some patients have to stop medication due to side effects. Unfortunately, we still do not have tests available to tell us which therapy works best for which patients. The answer to this question is of high importance. At present, many patients experience a phase of “trial and error” before a good therapy is identified. Failure to respond to treatment leads to frustration, depression and potential side effects from ineffective drugs.

Our project aims to predict therapy response to the commonly used drugs methotrexate and adalimumab. Our approach is different from already existing ones. Along with clinical data we also will collect information from affected skin but will not need biopsies. Instead we use a non-invasive tape stripping. We have used this method before and have optimised it so we can now detect thousands of proteins from each sample.

Due to the large amount of data collected it is impossible to analyse this information manually. We will therefore input all of the different and complex data into a “machine learning” computer program. Machine learning can be very powerful. Through many millions of calculations the computer is able to find “patterns” within very complex data. In our case we will look for the best “pattern” to predict response to methotrexate and adalimumab. We will share the program that we develop so that other researchers can use it to predict response to other drugs.

Latest results summary

Choice of therapy for moderate-to-severe plaque psoriasis is currently dominated by a trial and error. This project aims to identify means of predicting, before treatment, whether a patient will respond to a given systemic treatment by clinical data and skin samples. Direct sampling of a lesion classically involves an invasive skin biopsy but this project will use adhesive tape strips as a painless means of sampling. This will allow for many more patients to be recruited, allowing for the reasonable application of Artificial Intelligence (AI) analysis methods.

Recruitment has been delayed due to the pandemic, but is now proceeding at a rate of approximately 12 patients per month with a total of 35 so far. In the meantime, data from another project – focused on psoriatic arthritis – has been used to develop relevant methods and skills. Data gathered in these two trials is similar in structure and will likely face the same challenges in terms of format and missing data. Currently, recruitment is ongoing and processing of samples already collected is in progress. In addition, proteins of interest for measurement in the samples are being identified.

Professor Silvia Bulfone-Paus, University of Manchester

Psoriasis is a common, chronic, and as yet incurable inflammatory skin disease. Our project seeks to investigate the contribution of specific skin immune cells, namely mast cells and CD8 T lymphocytes (CD8 T cells), to the development of psoriasis. The latter have long been known to play a critical role in psoriasis, while the former cells have mainly been studied in the context of psoriasis-associated itch. Instead, here we explore whether mast cell-CD8 T cells interactions actually can drive the disease and are thus an important, new therapeutic target.

In psoriasis plaques, both mast cells and CD8 T cells are higher in number than in normal, healthy skin and appear to interact closely with each other. Furthermore, by isolating mast cells from skin biopsies and comparing their gene expression in healthy skin and in psoriasis plaques we have identified a number of secreted products or mediators of mast cells whose expression is increased in psoriasis and can regulate CD8 T cell activities.

Therefore, the overall goal of our project is to characterize the biological significance of mast cells-CD8 T cell interactions and how these may contribute to the development of psoriasis and their response to treatment. We also study how their activities are affected by biologic therapy targeting a key immune system molecule – interleukin (IL) 17. This knowledge will suggest novel strategies for therapeutic intervention, e.g. by manipulating mast cell mediators in psoriatic plaques so as to block the activation of CD8 T cell and thus reduce skin inflammation.

Latest results summary

The focus of this project is on mast cells and CD8 T cells, two immune cells that are enriched in psoriasis lesions. The hypothesis driving our study is that mast cells are critical modulators of pathogenic CD8 Tcell activities in psoriasis.This builds on work that has already been done in our lab that showed the increased gene expression of MC mediators that are capable of modulating CD8+ T cell activity in psoriasis skin. Our first aim was to identify the subpopulation of CD8+T cells that are dysregulated in psoriasis. To demonstrate that, we have designed a panelwith23 cell surface and intracellular markers and have optimized it. To establish a baseline, we analysed the blood samples from 8 healthy donors. In parallel, we have confirmed the spatial co-localization of mast cells and CD8 T cells in both healthy and psoriasis skin samples. In future, we will apply the established system to samples from psoriasis patients. We would like to investigate the alternation in mast cells and CD8 T cells as well as their connection with disease severity. We will also set up in vitro cell culture system to explore the mechanism and the factors that regulate the bidirectional interactions between these two cells.