Current Research

Dr Satveer Mahil, King’s College London

Powerful injection treatments that affect the immune system (‘biologics’) have revolutionised lives of people with psoriasis and are available for those with severe disease. Rising numbers achieve clear skin (‘remission’) within weeks but continue treatment indefinitely. This is costly and burdensome (infections/adverse events risk). When treatment is paused, psoriasis may not recur for some time, and then it recurs in the same location. This suggests skin retains an ‘inflammatory memory’, but this is underexplored. If we can monitor cellular/molecular signals before psoriasis re-appears, individuals could take treatment ‘as needed’.

We will:

1. Identify cell types in skin that underpin inflammatory memory in remission.

• We profiled skin biopsies from patients in remission on biologics using high-resolution ‘single-cell’ sequencing. Our analysis will characterise how each cell works and communicates with other cells during remission.

1. Understand cellular and molecular events in skin leading to recurrence.

• We profiled serial biopsies collected from the same patients after pausing biologics using single-cell sequencing. We will define the changes in skin that culminate in recurrence.

1. Investigate how the skin’s immune response could be monitored in blood for ‘as needed’ treatment.

• We will use blood samples (taken alongside skin samples) from the same patients and another group pausing biologics in our ongoing clinical trial. We will apply experimental techniques to detect events defined in (2) within blood.

Our research may inform personalised ‘as needed’ biologics use. This may reduce burden and cost of long-term treatment, enabling biologics access for more people with psoriasis for major health and quality-of-life benefits.

Dr Zenas Yiu, University of Manchester

Biologic therapies, which are treatments made from lab-engineered proteins, have helped many people with psoriasis achieve significant skin clearance and have been recommended as cost-effective treatments through a robust evaluation process. Recently, biosimilars—near-identical copies of biologic medicines—have been developed, offering the same effectiveness at a lower cost. However, the evaluation of the cost and benefits of these therapies have not been updated, leaving healthcare providers unsure whether they are using these treatments in the most cost-effective way.

 This research aims to fill these gaps by evaluating the cost-effectiveness of systemic therapies, including non-biologic, biologics and biosimilars for psoriasis. Using data from existing clinical trials and from the British Association of Dermatologists Biologics and Immunomodulator Register, a large multicentre registry of people with psoriasis based in the UK and the Republic of Ireland, we’ll study the orders of how these treatments are used over time, how effective they are at different stages of disease, and what happens when people switch from one treatment to another. We’ll also look at how factors like age or other health conditions might influence treatment success. 

 Finally, the project will develop a cost-effectiveness model to investigate which strategies for using systemic therapies provide the best value for money. This tool will help healthcare providers and policymakers decide which treatments should come first and which should follow. This will allow healthcare systems to allocate resources more efficiently while ensuring that people with psoriasis get the most effective care at the earliest time. 

Dr Satveer Mahil, King’s College London (Cecil King Memorial Fund Award)

Scientific research has delivered increasingly powerful injection drugs for psoriasis called biologics. These treatments are life-changing: more than half of patients receiving newer biologics achieve remission (i.e. clear skin) within a year. If treatment is started early, chances of achieving remission, and ultimately cure, are even higher. However, access to healthcare is poor and inequitable due to outdated, unsustainable hospital-centred healthcare models, which are not driven by the needs of affected individuals.

We will build on our existing co-developed self-report mySkin online platform (mySkin.org, >920 participants to date) and our ‘skin research inclusion toolkit’ (Choy et al, JEADV Clin Pract 2024; doi.org/10.1002/jvc2.516), to create a patient-centred digital healthcare tool (the mySkin app) for early, inclusive self-diagnosis, -monitoring and -management, which promises to transform healthcare efficiency and outcomes for everyone with psoriasis. We will deliver personalised evidence-based educational resources via the mySkin app on topical treatments (creams/ointments), and prevention and optimisation of associated health conditions for everyone with psoriasis. We will later assess feasibility of using the mySkin app for expedited face-to-face specialist review for those in need.

The mySkin app promises to deliver rapid reassurance and inform self-directed management when specialist review is not required, while releasing critical NHS capacity for review of those in need. Our work will ultimately drive a paradigm shift to inclusive, equitable data-driven patient-empowering care of psoriasis to transform health, quality-of-life and cost outcomes for all.

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 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.