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The Psoriasis Association is currently funding a number of psoriasis research projects, from improving UVB treatment to investigating the impact of flare-ups.
To find out more about an individual project, please click on the title to read the project summary provided by the researchers. Please see the glossary for an explanation of scientific terms used in the summaries.
Evaluation of Tumour Necrosis Factor Inhibitor Biosimilar Use in the UK: a study from the British Association of Dermatologists Biologics and Immunomodulator Register
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.
Identifying biomarkers of disease remission in psoriasis
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.
The APPLE Study – A Cross-sectional Observational Study Examining the Influence of Diet and Fasting on Psoriasis
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.
The impact of psoriasis on wellbeing and clinical outcomes in juvenile psoriatic arthritis
Dr Stephanie Shoop-Worrall, the University of Manchester
Around one in 14 children with arthritis have juvenile psoriatic arthritis. This means that alongside their swollen and painful joints, they also experience features of psoriasis or one of their close family has psoriatic arthritis. Although arthritis and psoriasis can separately impact the quality of life and wellbeing of a child, it is not known how having both arthritis and psoriasis adds to this burden.
We want to explore if children with psoriatic arthritis have worse clinical outcomes, quality of life, wellbeing and mood than children with other kinds of arthritis. We will then see if having active psoriasis is important in this burden. This will help us understand the experiences of children with psoriatic arthritis, and whether they might need extra services or care from different kinds of healthcare professionals when they are first diagnosed with psoriatic arthritis.
The second part of this project will explore how disease impact changes over time in children with psoriatic arthritis compared with other types of childhood arthritis. In previous work, we have found six different patterns of disease impact in childhood arthritis based on three core outcomes for childhood arthritis. In some groups, arthritis seems to improve but wellbeing does not. We want to understand if children with psoriatic arthritis are more likely to be in those groups and whether this is linked to having psoriasis early in disease. This will help doctors predict how disease activity will change over time when children are diagnosed with psoriatic arthritis and talk with families about how they can expect their child’s disease to progress.
This project will use information from the biggest collection of children with arthritis when they are diagnosed: the Childhood Arthritis Prospective Study. This study includes a large volume of information on wellbeing, mood, quality of life and information from hospital notes. This means that we will have the biggest collection of children with psoriatic arthritis from diagnosis, to allow us to study these important questions.
Predicting therapy response in 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.
Mast cell-CD8T cell interactions as drivers of psoriasis immune-pathogenesis
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.
Demonstrating the benefits of smoking cessation in psoriasis, a molecular approach
Dr Francesca Capon, King’s College London
Several studies have demonstrated that smokers are at increased risk of psoriasis. At the same time, it is not clear whether giving up cigarettes can improve disease symptoms. Our study will address this important question by:
- Identifying the changes that occur in the skin of smokers affected by psoriasis
- Demonstrating that these alterations can be reversed by quitting smoking
Thus, our specific objectives will be:
- To identify changes in chromosome conformation in psoriatic skin. Smoke can affect the way that genes and proteins are packaged together into chromosomes. As this can influence the activity of genes that contribute to inflammation, we will compare chromosome conformation in individuals with psoriasis and healthy volunteers.
- To demonstrate that the chromosome changes observed in psoriatic skin are linked to smoke. We will grow skin cells in a dish, in the presence of chemical substances that are found in cigarette smoke. We will then determine whether these chemicals can induce the same changes we observed in the skin of affected individuals.
- To show that giving up cigarettes can reverse the chromosome changes induced by tobacco. We will obtain skin biopsies from psoriasis sufferers who have agreed to stop smoking. We will determine whether their chromosomes are reverting to a normal conformation and whether this correlates with an improvement in disease symptoms.
Taken together, these experiments are expected to provide a scientific rationale for introducing stop-smoking programmes in the treatment of psoriasis.
Optimisation of NbUVB for psoriasis using a precision medicine approach (PHOTO-OPP study (PHOTOtherapy Optimisation Protocol in Psoriasis))
Dr Alison Havelin, Royal Victoria Infirmary, Newcastle
Psoriasis is a chronic skin disease affecting 2% of the UK population. It is a visible, often stigmatising disease and can have a significant impact on patients’ quality of life. UVB (ultraviolet B light) is one of the few psoriatic treatments that can lead to complete psoriasis clearance and a period completely free of psoriasis (remission) after treatment has stopped. For patients, this means living a life without the burden of applying messy topical therapies or taking potentially harmful medications to control their disease. The achievement of improved clinical remission with UVB is therefore highly attractive.
UVB is more effective in some patients than others, with 2/3 of patients achieving good clearance. The response to UVB is variable and currently there is no accurate way of predicting which patients will do better than others.
A typical UVB treatment course requires patients to attend hospital 3 times weekly for 6-10 weeks. Our recent study identified a subgroup of patients who were less likely to achieve clearance of their psoriasis, by analysing their response after just 3 weeks of treatment.
We hypothesis that by identifying these “slow-responders” early and changing their phototherapy regimens from three times per week to five times per week, they will have a better chance of clearing. To the best of our knowledge, this has never been studied before.
The optimisation of UVB treatments based on individual responses allows us to develop personalised treatment plans. This would benefit patients by reducing the need for potentially toxic systemic treatments and would result in better utilisation of NHS resources.
Evaluating the effect of cannabinoid-induced inhibition of FABP5 for the treatment of psoriasis
Dr David Hill, the University of Sunderland
Psoriasis is a chronic skin complaint characterised by raised red
patches of skin called plaques. These plaques are caused by the
over-production of skin cells, which in contrast to normal skin cells
that die and become replaced by healthy cells from below, fail to die
off correctly leading to thickened skin and impaired skin barrier
function. As a result, psoriatic plaques can often become inflamed
and painful. Unfortunately, despite the development of new
immuno-therapies there remains no cure. Therefore, to develop more
effective therapies for psoriasis we need a better understanding of
the underlying causes of the disease.
preliminary data and results from previous studies suggest that
psoriasis skin has increased expression of a protein called fatty
acid binding protein 5 (FABP5), which is responsible for controlling
the breakdown of a class of growth-regulators called
endocannabinoids, and has been linked to increased growth of several
cancers. We propose that endocannabinoids, which suppress the growth
of normal skin cells, are degraded in the skin of psoriasis patients
leading to increased cell production and defective skin barrier
formation. Our research aims to investigate how frequently levels of
FABP5 are increased in psoriasis by staining a small cohort of
affected and unaffected skin biopsies with antibodies that detect
FABP5. We will also reconstruct full-thickness skin in the lab from
normal skin cells that we have genetically modified to increase
levels of FABP5, which will tell us whether high FABP5 is sufficient
to cause psoriasis. Finally, because psoriasis skin likely has
reduced levels of endocannabinoids, we will investigate the effect of
cannabinoid treatment (and specific FABP inhibition) on the growth
and behaviour of FABP5-expressing skin cells.
Patients and health practitioners are increasingly looking at cannabis and cannabis-derived compounds as realistic and viable sources of medicine due to their excellent safety profile and changing legal status. However, the lack of preclinical evidence regarding disease-specific mechanisms and efficacy is a cause for concern. This study will allow us to better understand the role of cannabinoid signalling in psoriasis, which will form a rational basis for conducting future in-patient clinical trials.
Identifying immune determinants of clinical response to ustekinumab in psoriasis
Dr Paola Di Meglio, King’s College London
Biological drugs, such as ustekinumab (Stelara®), have a significant positive impact on the lives of people with psoriasis. Nevertheless, these expensive drugs do not work in every individual, and are still prescribed by trial-and-error. This process can be very frustrating for patients, and is not cost-effective for the NHS.
In order to prescribe the best possible drug to each individual with psoriasis, doctors need to be able to categorise people according to specific biological markers (“biomarkers”) that predict the likelihood that the drug will work. The Psoriasis Association-endorsed Psoriasis Stratification to Optimise Relevant Therapy (PSORT) is a multicentre study aimed at identifying biomarkers predictive of response to biologic drugs.
As part of PSORT, we are looking specifically at the white blood cells as potential predictive biomarkers. We aim to analyse cells already obtained from the blood of patients receiving ustekinumab, and measure a number of biological markers associated with them. Moreover, we will apply mathematical and statistical techniques to understand whether any of the biological markers measured can predict whether or not each individual patient will do well on ustekinumab.
Our findings will eventually be integrated with other datasets currently produced by PSORT (e.g. genetic data) to produce a clinically useful tool (“stratifier”) to guide psoriasis management, for the benefit of people with psoriasis, and to reduce costs for the NHS.
Latest results summary
Biological drugs, such as ustekinumab (Stelara®), have a significant positive impact on the lives of people with moderate-to-severe psoriasis. Nevertheless, ustekinumab does not work in every individual. To prescribe the best possible drug to each individual with psoriasis, doctors need to be able to classify people according to specific biological markers (“biomarkers”) that predict the likelihood that a specific drug will work. In this PhD project, we are analysing white blood cells in the blood of people with psoriasis receiving ustekinumab and measuring a number of biological markers associated with them. In the first year of the project, we have developed a laboratory test to measure the effect of ustekinumab in specific white blood cells and applied this test to the first 10 samples from people with psoriasis. Moreover, we have applied mathematical and statistical techniques to understand whether any of the biological markers measured can predict whether each individual will do well on ustekinumab. Preliminary data suggest that some types of white blood cells may be more sensitive to the effect of ustekinumab and this may be associated with whether the drug works or not. Next steps will involve increasing the number of samples and analysing more biological markers with the aim to further verify and expand our findings. Taken together, our project has the potential for identifying biomarkers in the blood of people with psoriasis to predict response to ustekinumab, for the benefit of people with psoriasis, and to reduce costs for the NHS.
Impact of autophagy and nucleophagy deregulation in psoriasis
Dr Daniele Bergamaschi, Queen Mary University of London
Autophagy is a detox process naturally supporting the epidermis in cleansing and replacing damaged cells in exchange of energy. This is a crucial mechanism as one of the main skin functions is to protect the organism from UV exposure and infections.
When keratinocytes are surrounded by inflammatory cells for a prolonged time, they lose their ability to detox and replace damaged cells. Inflamed skin cells release toxic substances (Reactive Oxygen Species) which reduce their healthy ability to purify themselves thus preventing them to transform their shape and size. We have recently shown that when skin cells detox, they also gradually lose their nucleus with a process called Nucleophagy. This mechanism is not correctly functioning in the few skin diseases including psoriasis.
In this project we will further determine the effects of inflammation on the autophagy machinery in healthy human and psoriatic epidermis and will establish the consequences of having a deregulated form of this metabolic process. This will be achieved by measuring where the protein involved in the autophagy process of the skin are expressed and whether they are correctly functioning. As a model we will use cell lines isolated from normal and psoriatic skin and with them we will also reconstruct in 3D psoriatic-like artificial skin to perform experiments of drug treatment.
This research project will significantly improve our understanding of how this detox metabolic mechanism can impact on development of psoriasis and may lead to the identification of novel therapeutic and preventative targets for this common skin condition.
Latest results summary
In this first part of the project we have been trying to study and characterize the differences between human normal and psoriatic skin keratinocytes. These cells were isolated from either normal or psoriatic skin samples and immortalized in the lab, allowing us to measure important parameters in a simple live model. For example, we have been growing them in the lab and tested their ability to detox. Our preliminary evidence suggest that psoriatic skin cells have a reduced capacity to eliminate their damaged or surplus cytoplasmic material. We are now investigating when exactly this defect is picked up by psoriatic cells and whether we can reproduce the same defect if we chronically expose normal skin cells with inflammatory stimulants.
We are also imaging human skin samples from both healthy and psoriatic patients. We stain our samples with immunofluorescent protein tags which show us where in the skin certain detox pathway proteins are expressed. We will compare the amount and location of these detox proteins between healthy and psoriatic skin samples to determine if there any significant differences and where these differences are in the separate layers of the skin.
All the information in this part of the project will guide us in the next step of the study, where we will develop different 3D psoriatic-like artificial skin models and investigate how inflammation can affect the skin detox ability.
Investigation of the prevalence of liver fibrosis in patients with psoriasis using Transient Elestography and evaluation of the relationship between liver fibrosis and methotrexate
Dr Parastoo Babakinejad, Royal Victoria Hospital, Newcastle
Patients with psoriasis appear to have higher rates of liver fibrosis in comparison to the general population. The prevalence of liver fibrosis in the psoriasis population in the UK has not been defined. The higher rates of risk factors for liver fibrosis such as obesity, alcohol and diabetes are important; however there have been concerns that methotrexate can contribute to liver fibrosis. Despite the increasing importance of biologic therapies, methotrexate remains the most commonly used systemic agent in the UK. The majority of patients needing systemic therapy will try methotrexate first as per NICE guidance.
This study aims to investigate the prevalence of liver fibrosis in a group of patients with psoriasis by measuring liver stiffness measurement (LSM) using Transient Elastography. The cumulative methotrexate dose in addition to other important factors including BMI, waist circumference and alcohol intake will be recorded. A univariate analysis will be performed to investigate the relationship between all measured factors and LSM. The relationship between the cumulative dose of Methotrexate and liver fibrosis will be addressed.
The ultimate goal is to use the prevalence data to perform a power calculation to determine the number of participants required to conduct a study to determine which factors can predict the risk of liver fibrosis and whether or not methotrexate is an independent risk factor for liver fibrosis in patients with psoriasis. Using this data a risk prediction model can be built to allow optimal and safe prescribing of methotrexate.
Investigating genetic control of the psoriasis transcriptome to define and validate drug and disease endotypes
Professor Nick Reynolds, Newcastle University
The genetics underlying psoriasis differs from person to person. Currently we have no way of knowing which treatment will work best for each patient and so treatments are prescribed by trial and error. As a result, only 50% of patients remain on their original drug 3 years later, which is not ideal for the patient and is wasteful of NHS resource. We need to find the right treatment, at the right time for the right patient: an approach known as personalised or stratified medicine. Our Consortium (PSORT) aims to develop tests based on blood samples or a small skin biopsy that predict individual patient responses to biologic drugs. This project builds upon the extensive clinical and sample resource already collected by PSORT.
Developments in gene sequencing mean that we can now sequence all the messenger RNA molecules present in the skin or blood of an individual at reasonable cost. We will combine this information with the genetic makeup of individuals to produce markers of clinical response. Such complex data requires high-level computer analysis combined with biologic and clinical interpretation. As bioinformatics (a discipline involving method development and analysis of biological data) is a rapidly growing and developing field, this represents an ideal PhD project.
Our established collaborative network provides an excellent training environment for a PhD studentship and will develop cutting-edge transferable skill sets for the next generation of researchers. Key outcomes will include biomarkers that can be developed into clinical tests that predict individual patient response to biologic drugs.
Latest results summary
In the past decade a new class of psoriasis treatments have emerged called “biologics.” Several different biologics are available and currently we have no way of knowing which will work best for each patient. This means that biologics are prescribed in a “trial-and-error” manner, which is detrimental to patient wellbeing and also wasteful of NHS resource. Therefore, an important goal in psoriasis treatment is for each patient to be prescribed the right biologic for them straight away. This will not only require deeper understanding of psoriasis and its molecular subgroups (“disease endotypes”) but also the mechanisms by which these drugs work (“drug endotypes”). In order to investigate these disease and drug endotypes, a multi-centre consortium was established called PSORT (Psoriasis Stratification to Optimise Relevant Therapy). The ultimate aim of PSORT is to develop tests based on blood samples or a small skin biopsy that predict individual patient responses to biologic drugs. In order to achieve this PSORT has recruited a cohort of patients commencing treatment with either adalimumab or ustekinumab, two commonly prescribed biologics. Skin and blood samples were collected from these patients before commencing treatment, and one week and twelve weeks after commencing treatment. The messenger RNA (mRNA) in these samples was then sequenced, providing us with data indicating the levels of gene expression in these patients at each of these time points. This has allowed us to identify a number of gene expression patterns that not only describe the biological mechanisms by which these drugs work, but also predict clinical response to these drugs. Genetic data from these patients has also allowed us to identify genetic variants that influence gene expression, and work is currently underway to associate these variants with clinical response.
Investigating the therapeutic benefits of exercise in patients with psoriasis.
Dr Helen Young, University of Manchester
Psoriasis, a common skin disease which confers immense suffering on those it afflicts, is associated with an increased risk of developing cardiovascular disease (CVD). The severity of psoriasis and the number of individuals affected by the disease are increased by obesity. Patients with psoriasis are often embarrassed about exposing their skin in front of others, which leads to exercise avoidance. Lack of physical exercise and obesity are risk factors for the development of CVD.
Individuals with psoriasis have much to gain by regular exercise including an improvement in psoriasis itself, a reduced risk of CVD, weight management and enhanced wellbeing. Based on our research in this field, which was supported by a Psoriasis Association PhD studentship, we worked with individuals with psoriasis to develop an exercise programme that can be followed by sufferers – even on their worst day. This project will test our exercise programme in clinical practice and measure the improvement in psoriasis, CV health and overall well-being in patients. We will also use a laboratory-based technique called transcriptomic analysis to investigate how exercise exerts its beneficial effects in the body. We will learn more about psoriasis and how to treat it effectively.
An attentional bias approach to understanding and reducing the psychosocial burden of psoriasis.
Dr Henning Holle, University of Hull
People with psoriasis often experience social rejection. A big risk in this context is that psoriasis can lead to a spiral of increasing social isolation, driven by a fear of negative social reactions. Every time a person with psoriasis experiences such a negative social reaction, the link between fear, avoidance and further social withdrawal is reinforced. At the same time, the person may become more likely to always carefully monitor the environment for signs that others might reject them, for example, by showing facial expressions of disgust. In the medical literature this state is known as hypervigilance, which can lead to a cascade of negative thoughts and emotions, increased anxiety and exhaustion.
The present research project aims to determine whether people with psoriasis can learn to escape the vicious and mutually reinforcing cycle of fear and increased attention towards potential social threats. In a first step, we will systematically document the degree to which people with psoriasis show hypervigilance or increased monitoring for different types of information (disease-related words, facial expressions of disgust, bodily expressions of disgust). Once we have determined this, we will investigate in a second step whether people with psoriasis can be trained to allocate attention in a more balanced way, and whether such a training can increase resilience, reduce anxiety and thereby help to reduce the psychosocial burden of psoriasis.
Latest results summary
Fear can be a double-edged sword. It allows us to detect danger in the environment and helps us to respond effectively to threats. But there is evidence that devoting too much attention to threat-related information can lead to the development of anxiety disorders. In our research project, we investigate whether such an attentional bias contributes to the psychosocial burden experienced by people with psoriasis. So far, we found that words related to the disease (such as flaking) do not capture more attention in people with psoriasis. This is not what we predicted, and it might be due to the fact that words are not able to capture attention in such an immediate manner as images are able to. In the next year, we will study this in more detail by presenting images of facial expressions (for example, a person looking either disgusted or neutral) to people with psoriasis and a control group. The overall aim is to understand how attentional bias towards threat-related information contributes to social anxiety in those affected by psoriasis. This could lead to developing novel interventions designed to reduce the psychosocial burden of the disease. To find out more about the research, including how to take part, please email S.Ettyfirstname.lastname@example.org or visit her blog https://abpsoriasis.blogspot.com/ .
Mutation burden of narrowband UVB
Professor Eugene Healy, Southampton University
Ultraviolet radiation (UV) in sunlight is an effective treatment for psoriasis. Narrowband UVB (NB-UVB) is a form of “artificial sunlight” which is used widely by dermatologists to treat patients with psoriasis. It is known that UV can cause skin cancer, but the long-term safety of NB-UVB in relation to skin cancer development is unknown. It has been highlighted that, in order to determine the long-term safety of NB-UVB, large studies in multiple dermatology centres involving several thousand new patients per year would need to be conducted and that those patients would need to be followed up at least for 10 years or more. In the meantime, patients with psoriasis and dermatologists do not know what is a suitable safe limit of NB-UVB treatments for people with psoriasis to have over the course of their lifetime.
All of the cells in our body contain the genes that we are born with. These genes are written in the DNA in all our cells, including our skin cells. Exposure of the skin to UV causes specific damage to the DNA in skin cells and leads to mutations (i.e. errors in the DNA) that affect the ability of the genes to work properly. When a skin cell divides these changes are passed on to its daughter cells. Over time, these daughter cells and their descendants (which are collectively known as a clone) may eventually accumulate thousands of mutations which may cause the skin cells to become abnormal and form skin cancers. Recent advances in genetic technology have allowed scientists to map groups of cells carrying altered genes which drive the formation of cancer in normal skin. In the proposed study, we plan to use this technology (called next generation sequencing) to detect how many groups of cells carrying DNA changes linked to cancer are induced by NB-UVB treatment for psoriasis. Based on these findings, we will calculate the additional risk of cancer in a psoriasis patient resulting from multiple courses of NB-UVB and thus estimate the long-term safety of NB-UVB.
Latest results summary
Narrowband UVB (NB-UVB) is used as a treatment for psoriasis but it is also known that ultraviolet radiation has the potential to cause skin cancer. To identify how many courses of NB-UVB a patient can receive over their lifetime without being at significant risk of developing skin cancer, the changes in genes within the DNA in skin cells after a course of NB-UVB are being investigated.
Skin samples have been collected from 20 individuals with psoriasis before their NB-UVB treatment to date. Of these 20 samples, so far 13 have provided a subsequent skin biopsy sample after the course of NB-UVB treatment (the others are still receiving their course of NB-UVB). These samples will be sent to the Wellcome Sanger Institute in Cambridge in the near future to identify changes in genes via Next Generation Sequencing (NGS).
Experiments have been conducted to ensure that the DNA from these skin samples is of sufficient quantity and quality for NGS. In preparation for the analysis of genes relevant to skin cancer in the NGS data that will be generated from the skin samples, publicly-available online genetic databases such as COSMIC (i.e. Catalogue of Somatic Mutations in Cancer) and genetic data obtained via a systematic literature search have been collated. Bioinformatics tools have been used to organise and analyse the data (while at the same time allowing the PhD student to gain bioinformatic skills and experience in this type of analysis). Statistical tools have been employed to identify significant cancer-causing genes (known as driver genes) in this data. This information will be utilised in the analysis of the NGS data that will be generated from the above skin samples taken from individuals who have received a course of NB-UVB, with the results of that analysis allowing us to determine the long-term safety of treatment with NB-UVB.
The risk of cancer in psoriasis patients treated with biologic therapies compared with conventional systemic therapies: results from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)
Professor Richard Warren, University of Manchester
Patients with severe psoriasis (more than 10% of the body surface affected) are often offered two broad types of long-term systemic treatment: conventional systemic treatments, such as methotrexate, ciclosporin and acitretin; and biologics, such as Humira, Stelara, and Enbrel. Biologic therapies target the immune system and may affect the body’s ability to fight cancer. It is not known whether being treated with biologic therapies carries an increased risk of cancer in psoriasis patients compared to treatment with conventional systemic treatments. Very few studies have compared the safety of these two treatment options and have been limited by short duration with only small numbers of patients. As cancers develop relatively rarely, we need to compare large groups of psoriasis patients receiving biologic and conventional systemic treatments respectively.
Latest results summary
Biologic therapies are injectable treatments for people with severe psoriasis who no longer respond to treatment with traditional oral systemic agents. There are some fears that people with psoriasis treated with biological therapies might have an increased risk of developing cancer compared with people treated with the older systemic therapies.
The first study of this project reviewed all the published evidence to date pertaining to the risk of developing the skin cancer, known as melanoma, after receiving treatment with biologic therapy for either psoriasis or conditions treated with the same biologics. Due to the small number of studies in psoriasis, we were unable rule out an increased risk of melanoma in patients treated with biologic therapy. These findings have only highlighted the urgent need to clarify if treatment with biologic therapy is a risk factor for cancer.
The next step of the project will aim to address this research question by exploring if the people with psoriasis, in the UK and the Republic of Ireland, treated with biologic therapy are at an increased risk of developing common cancers (breast, prostate, lung, colorectal and melanoma) compared with people treated with only non-biologic systemic therapies. The study will utilise data from The British Association of Dermatologists Biologics and Immunomodulators Register; known as BADBIR.
A pilot study to compare the response of psoriasis to narrow-band UVB phototherapy in the morning and afternoon
Dr Henry Grantham, Royal Victoria Infirmary, Newcastle Upon Tyne
Psoriasis is a very common skin disease. We often think of psoriasis as a disease of just the skin, but research shows that people who have psoriasis may have different body clock rhythms from the general population. We know that people without psoriasis are more sensitive to phototherapy with ultraviolet B light at different times in the day. What we don’t know is if this is also true for people who have psoriasis.
The main aim of this research question is to see if patients' psoriasis is more sensitive to ultraviolet light at different times of the day.
We also aim to see whether the participants in our study have different body clock (circadian) rhythms to the general population. We will do this in multiple ways, such as looking at the levels of a few chemicals in the body that respond to body clock rhythms (melatonin and cortisol), asking questions about participants' sleep (by questionnaire), measuring sleep (with a wrist-worn motion sensor), and asking the patients to fill in questionnaires about depression.
We will recruit 15 patients who have been prescribed phototherapy for the treatment of their psoriasis. The study will last nine days per patient and after this they will proceed to their prescribed course of phototherapy.
Latest Results Summary
Humans, like in all living creatures, have an internal clock, or circadian rhythm. This means that expression of our genes and proteins changes throughout the day. Over the past few years, research into this has grown to become a huge discipline that aims to streamline and personalise medical treatment for people. In the same year the Nobel Prize was awarded for circadian rhythms, Professor Reynolds and I were awarded a Small Project Grant by The Psoriasis Association to set up, to our knowledge, the first research project looking into circadian rhythms in the skin of people with psoriasis. We also aimed to look into whether ultraviolet light affects psoriatic skin differently in the morning and afternoon, to see whether phototherapy – which is an ultraviolet light treatment given to people with psoriasis in hospitals – is better at a certain time of the day.
To this end, we have used the money to train a cohort of dermatology research nurses in how to administer UV light, how to read the results and how to take skin samples (our main source of research data). It hasn’t always been smooth, however! The field is always evolving, and so we have had to adapt our research to take into account new information. The Covid-19 pandemic has unfortunately been a big set-back for our study, initially halting all recruitment for six months. Once again, we had to modify our study, to make it safer for participants so we can continue to recruit. The pandemic has also changed our focus to analysing the data we have so far. Although it is from only five patients, we have forty skin samples – half of which are being analysed for gene changes and half for protein changes.
Ultimately, this is a pilot study, which means it aims to inform future research, but so far it has generated quite a lot of exciting data which we will share with you when we can. We are very grateful to you all for making this possible, and still look forward to a future where doctors personalise your treatment based upon your internal clock.
An innovative mixed methods study investigating altered emotional processing in psoriasis patients
Dr C. Elise Kleyn, University of Manchester
Psoriasis is a chronic, inflammatory skin disease which affects 2-3% of the UK population. As a result of the appearance of their skin, patients with psoriasis commonly experience negative social interactions and reactions from others including facial expressions of disgust.
Our group were the first to use brain scanning (magnetic resonance imaging) to demonstrate that patients with psoriasis process facial expressions of disgust differently to individuals without skin disease. It was demonstrated that patients with psoriasis have a diminished signal in the insula, an area of the brain known to be important in disgust processing. This differential response may reflect a coping mechanism, adopted by patients to ‘block out’ the aversive reactions of others and protect themselves from stressful emotional responses.
More recent, (unpublished) work, by the group suggests that an individual’s response to disgust may vary depending on the length of time a patient has had psoriasis and the age at which they were diagnosed. However, it is not known when this mechanism develops, or its wider implications on patients’ quality of life.
This novel study will pilot the integration of different techniques, including in-depth patient interviews and state-of-the art brain scanning, to further understanding of this proposed coping mechanism in psoriasis. Addressing this current gap in knowledge will inform the development of personalised clinical and psychological interventions to support people living with psoriasis.
Neuropsychological morbidity in psoriasis
Dr Elise Kleyn, University of Manchester
Psoriasis is a chronic skin disease for which there is currently no cure. It afflicts far more than the skin and there is limited knowledge of the mechanisms or way in which psychological effects as well as other brain effects are caused.
We were the first to use brain scanning techniques to show that patients with psoriasis process facial expressions of disgust differently to individuals without skin disease.
This PhD project will use state-of-the-art brain scanning, questionnaires and laptop-based tasks to investigate whether treating psoriasis lesions effectively will change altered processing of disgust in patients. Patients’ reactions to pictures of their own psoriasis lesions and those of others will also be studied in a separate group of patients who have had psoriasis for varying lengths of time.
Understanding the brain-skin connection is key to developing new approaches to help treat the psychological and other brain effects of psoriasis.