Jorge Georgakopolous, Western University
Psoriasis is a chronic autoimmune skin disease affecting one out of fifty people in Western countries. This systemic illness is most commonly presented in the form of plaque psoriasis; raised, red patches with a silvery white build-up of dead skin. These plaques are often found on one's scalp, knees, elbows, and lower back and can be socially and physically debilitating for an individual.
It may be too early to scream success, but scientists are very excited over a new crop of biological drugs that have shown unprecedented ability to clear moderate to severe plaque psoriasis. Cosentyx (also known by its generic name secukinumab) is the first developed drug in the new class of interleukin-17 (IL-17) inhibitors to be approved by Health Canada in February 2015 to treat moderate to severe plaque psoriasis in adults. IL-17 is a naturally occurring protein found in the skin of healthy individuals required for wound healing and fighting infection. In someone with psoriasis, over-activation of IL-17 occurs with an unknown reason. High concentrations of IL-17 are often found in the skin of psoriasis patients, as such, the ability of Cosentyx to reduce IL-17 levels can help clear psoriasis.
Prior to the development of Cosentyx, a significant gap existed in the treatment of moderate to severe plaque psoriasis. In 2015, Novartis announced the results of their two-year Phase III trials demonstrating Cosentyx treatment leads to significant reduction or clearance of plaque psoriasis. Despite such promising results, there is currently no understanding of the efficacy and safety of Cosentyx use in our very own hospitals. Today, physicians around the world are prescribing Cosentryx based on safety profiles from these relatively short clinical trials that simply fail to address all concerns related to adverse drug reactions.
For the first time ever, a research team from Sunnybrook Health Sciences Center and Women’s College Hospital in affiliation with the University of Toronto hope to fill the void in our current understanding and truly unravel what risks patients who receive Cosentryx are faced with.
Arvin Ighani, University of Toronto
Psoriasis is a chronic disease that results in itchy and scaly patches on the skin. The disease is widespread and affects more than 125 million people worldwide. Unfortunately, the cause of psoriasis is unknown and no cure exists. As such, current therapies focus on management of the disease. Many patients present with different forms of psoriasis and the underlying mechanism causing the disease may vary slightly from person to person. A myriad of genetic and environmental factors contribute to the end outcomes and severity of psoriasis presented in each individual patient. As a result, not all treatment options work the same way for the millions of patients with psoriasis.
Recently, a new drug called Apremilast was approved for the treatment of moderate to severe psoriasis. It is the only currently available drug that treats psoriasis by inhibiting an inflammatory enzyme called phosphodiesterase 4 and thus offers a unique solution for patients who have exhausted other treatment options. Clinical trials of the drug show an incredible 75% reduction in the severity of psoriasis in 28.8% of patients, but there is little data examining the use of the drug in real-world practice. Therefore, our study aims to measure the safety and efficacy of Apremilast in the treatment of moderate to severe psoriasis in the real world setting in two academic clinics at the University of Toronto by collecting data from over 100 patients taking the drug. This project has the exciting potential of cementing Apremilast as a new, efficacious drug that can be used to treat thousands of patients with psoriasis and may change the landscape of current treatment options for psoriatic patients around the world.
Ryan Lewinson, University of Calgary
Psoriasis, a skin disease characterized by scaling skin lesions, affects nearly one million Canadians, and about 30% of individuals with psoriasis will experience progression to psoriatic arthritis – an inflammatory disease that not only includes psoriasis symptoms, but also severe joint pain and irreversible joint damage. It has been shown that psoriasis and psoriatic arthritis are both associated with abnormally high levels of an inflammatory protein naturally found in the blood giving rise to the possibility that this protein plays a central role in the progression from psoriasis to psoriatic arthritis. Interestingly, it has recently been found that individuals with depression also tend to exhibit increased concentrations of this protein. Depression is very common in individuals with psoriasis and psoriatic arthritis, and since depression causes changes in the levels of the same inflammatory protein, there is a possibility that depression may place individuals with psoriasis at greater risk of developing psoriatic arthritis. In this study, we will be evaluating this relationship by studying medical records data from the United Kingdom, where records are available on over 12,000,000 patients, with up to 28 years of follow-up time. First, we will identify those diagnosed with psoriasis, and then divide the group based on whether or not they experienced a diagnosis of depression after their psoriasis diagnosis. We can then identify those individuals who eventually develop psoriatic arthritis, and determine if psoriasis patients with concurrent depression were more likely to develop psoriatic arthritis than those with psoriasis and no diagnosis of depression. Using statistical modeling techniques, we can also take into account the medications that these individuals were using, and also any other diseases they may have had that could contribute. This will allow us to identify the specific risk that depression has on the progression of psoriasis to psoriatic arthritis. This study could provide clues to further our understanding of how these diseases occur, and most importantly, highlight a very clear strategy to prevent psoriatic arthritis: monitoring and, if needed, treating psoriasis patients for depression.
Vivian Szeto, Toronto Western Hospital
Psoriasis is a chronic skin condition that affects 2-3% of the population. Those afflicted with this skin disorder have an increased risk of developing psoriatic arthritis and as a result they are often treated by both dermatologists and rheumatologists. In 2006, the University of Toronto established a cohort of patients with psoriasis who lacked arthritic symptoms. These patients participate in clinical research in our Psoriatic Disease Program, attending annual follow-up at the Toronto Western Hospital with a standardized protocol. We also follow and treat many patients with psoriasis who elect to not participate in clinical research.
This study aims to determine whether or not the clinical outcomes of psoriasis patients who participate in clinical research differ from those who do not. This is important in that we need to confirm that what we find in our clinical research program applies to all patients with psoriasis, not just those who participate in research.
The student will review the charts of patients followed in the Dermatology Clinic who have chosen not to participate in research and collect information that will then be compared to the information on patients who participate in the clinical research which is already available in the research clinic database.
Laila Zaman, Toronto Western Hospital
Psoriasis is a common immune-mediated skin condition found in 3% of individuals. Almost a third of individuals with psoriasis develop psoriatic arthritis (PsA), a chronic inflammation of assorted joints throughout the body. The causes of PsA and psoriasis are not well known, but likely involve the interaction of genes and the environment. Epigenetics, or modifications that sit on top of DNA and alter its function without affecting the DNA sequence, may play an important role in psoriatic disease. In sperm cells from patients with PsA and psoriasis, we identified several genes that were affected by a type of modification that is used to control gene expression. If these modifications are also detected in other cells in the body, they could play an important functional role in psoriatic disease. This study will determine if there is a correlation between the epigenetic changes and the functional expression of these genes in cells throughout the body. This would increase our understanding of the biology of PsA and could provide new targets for pharmaceutical therapies. Furthermore, these genes may serve as markers of PsA for early detection and treatment.
WanLi Zhou, University of Toronto
Psoriatic arthritis (PsA) is a disorder that affects various joints of the body. It affects up to 30% of patients with existing psoriasis. Many patients with PsA experience reduced quality of life. The causes for the development of the disease are currently unknown. Physical trauma and mechanical stress have been considered as potential important factors contributing to the development of joint damage in PsA.
In this study, we plan to assess whether exposure to physical and mechanical stress from job conditions is associated with the development of joint damage in patients with PsA.
Research Approach: We plan to administer a survey about job history since the age of 18 to a large group of PsA patients who have been diagnosed with this condition for at least 10 years. We will look to see if there is a connection between the kind and level of physical stress encountered during jobs and the degree of joint damage on X-ray. Based on these results, we will perform statistical analysis to test whether an association exists.
In this study, we hope to identify a new risk factor that may play a part in the development of PsA. We hope this will help us understand how the disease develops and progresses. In addition, it may help us recognize patients who are at increased risk of developing PsA and predict the way their disease will progress. This may ultimately tailor their treatment plan and improve their quality of life.
CAPP is so grateful for the support of our 2016 sponsors, without whom these Studentships would not be possible.