Psoriasis is a skin disease that causes red, itchy, and scaly patches that can become very painful. While a common disease, affecting more than 125 million people worldwide, it’s a chronic disease with no known cure. Different types of psoriasis cause varying types of patches that range from moderate to severe. Fortunately, treatments, lifestyle habits, and coping strategies can help patients manage their disease throughout their lives.
Psoriasis is a common disease, affecting more than 125 million people worldwide. However, it’s a chronic disease with no known cure. Read our experts’ insights and find out about our experience in psoriasis clinical research.
October 29 is World Psoriasis Day, an annual day devoted to people with psoriasis/psoriatic arthritis. It is a day that was started by psoriasis patients, for psoriasis patients.
In light of World Psoriasis Day, we spoke with Rachel Peterson, MD, FACR, Medical Director, Medical Affairs and Rahul Patel, Senior Medical Director, Medical Affairs about their experiences in the therapeutic area of psoriasis, as well as current and future therapeutics that will aid in psoriasis treatments.
Tell us about your experience and expertise in psoriasis, as well as PRA’s general experience and expertise in this area.
Rachel: I have a rheumatology-centered background with regard to psoriasis. As part of our rheumatology fellowship training and subsequent clinical practice, we tend to see a fair amount of patients who have psoriasis and accompanying psoriatic arthritis. At PRA, members of our rheumatology group share that clinical background prior to coming into the medical monitoring experience for this disease space.
In terms of my experience with psoriasis at PRA, I’m currently a Medical Monitor for two large psoriasis studies. One is a pivotal, phase 3 “parent” study that feeds into a second, long-term follow-up study. The pivotal phase 3 study is due to finish before the end of the year, with results expected early 2021. It’s an exciting time, and we are hopeful it will bring positive results and add to the available therapies for psoriasis.
Rahul: My experience as a Medical Monitor/Medical Lead includes working on a large, phase III psoriasis program for a major pharmaceutical sponsor. I’ve also worked with that same pharma partner in terms of the general development program for the same compound, an oral study medication, in other therapeutic areas. For PRA as a whole, having a strong partnership also gives us the benefit of understanding the study drug in more detail and awareness of the full development program for the compound.
PRA has been fortunate to have this partnership with the same pharma sponsor and opportunity to manage these large psoriasis studies going back to their initial design and start of recruitment. Overall, it's been a successful partnership.
Psoriasis is a condition primarily affecting the skin, but can you each talk us through other hurdles psoriasis patients face?
Rachel: There are definitely numerous hurdles in terms of psoriasis patients facing other physical diseases. Often, these patients have other comorbidities that place them in a high cardiovascular risk profile.
Additionally, there's a significant psychological toll of psoriasis.. Affected patients are more prone to depression, anxiety, and even suicidality. Much of this is due to the appearance of their skin and the social impact it can have. Patients with psoriasis may feel isolated, embarrassed, stigmatized or discriminated against because of the appearance of their skin. There also often exists a misperception that psoriasis is contagious or infectious.
Encouragingly, there appears to be an increasing awareness of these concerns in the medical community, and efforts to help affected patients manage this aspect of their diagnosis. There is a great need for a more holistic approach to treating psoriasis patients. This approach includes screening for these psychosocial aspects of psoriasis as well as proactively referring patients for any mental health assistance they may need.
Rahul: Psoriasis should also be considered as a systemic immune disorder. Like many other autoimmune diseases, it’s possible for psoriasis to be associated with higher risk of cardiac coronary disease and cardiac complications due to continued inflammation within the body. It can even be associated with ocular involvement and inflammation in joints and tendons, as well as spine as part of the spectrum of the condition.
Psoriatic arthritis can develop from psoriasis. Patients can present first with the arthritis and they might have subtle skin involvement. In such cases, we may only see the full psoriasis skin involvement later, well after the psoriatic arthritis. More commonly, the skin involvement is quite evident, and the arthritis might be noted or developed later. Again, we can’t necessarily predict the patients who may be more likely to have that type of complication. Roughly around one third of those patients with general psoriasis will have associated psoriatic arthritis.
Psoriatic arthritis tends to be much more physically debilitating than general psoriasis. Like many other autoimmune conditions, it involves more than just the primary target organ, which is the skin in this case. It can adversely affect joint health and indeed movement. It can also have various complications and impact on quality of life separate from just the psoriasis in terms of joint functions and daily activities.
All of these insights and factors must be taken into account when clinicians are treating these patients and weighing treatment options.
Rachel: Historically, psoriasis and the associated psoriatic arthritis were treated similarly to other types of inflammatory arthritis, such as rheumatoid arthritis. There is some overlap in the medications used to treat these two diseases, although more recently there's been improved research into what different underlying mechanisms of action might exist and be targeted, so more effective in psoriasis versus in another inflammatory arthritis. The damage that psoriatic arthritis causes is permanent and debilitating, and so there's an urgency to give these patients the treatment they need in order to stop joint damage and preserve function.
Thankfully, we have a growing armamentarium in terms of effective, disease-modifying medications that are available to treat psoriasis and psoriasis arthritis, with newer therapies such as biologics and small molecules being added to the older medications like methotrexate.
Are there more curative therapeutics in the pipeline that could better serve psoriasis patients?
Rachel: In recent medical history, there have been many advances in immunology and rheumatology, as well as in our more precise understanding of the immune system. For psoriasis, we now understand that specific kinds of cytokines can lead to the development of this condition, and have translated that into further research. This has led to a number of novel, effective treatments, and I anticipate this will continue with future research.
More recently developed treatments have focused on targets like IL-12 inhibitors, IL-23 inhibitors, and IL 17 inhibitors. This is a recently expanding space. Thinking a step beyond that, we're learning that in different individuals with the same disease, different cytokines and inflammatory pathways may be more important in driving the disease. This means that while a certain medication works in one patient with psoriasis, it may not be effective (or may be less effective) in another patient with psoriasis.
I think the future of psoriasis treatment ultimately lies in identifying and targeting specific genes involved in the disease process, in order to better individualize therapy. Individualizing therapy through identifying an individual’s particular inflammatory immunological process that drives their disease is crucial to understanding how to best treat it.
Rahul: Unfortunately, there’s no true cure for psoriasis, but we are definitely getting much closer to one. We’re approaching therapeutics in ways that can lead to significant improvement, clearance of nearly all skin lesions, and treatment of general features of the condition, beyond the skin. There's a clear unmet need, even with the variety of approved treatments available now, especially with no definite cure. The reassuring news is that many patients can be put into remission through the use of current therapeutics.
Some limitations of current biologic treatments, however, are that many of these biologic medications must be taken by injection or IV infusion. Some next-generation therapies are oral medications that patients can take in the comfort of their home. PRA is fortunate to be working on some of those studies with oral agents.
Just over the last decade or so, we've significantly raised the bar in terms of what we expect in therapies for psoriasis. It’s gotten to the point where even very high endpoints such as the PASI 100, which means essentially 100% clearance of all psoriasis skin manifestations, have become a common endpoint in many psoriasis studies.
Basic research over the last several decades has led to significant understanding and advancements in treating abnormal immune system activation. The patient community with psoriasis, as well as the medical community, have been fortunate to those discoveries translate into therapeutics that have transformed many patient’s lives.
I want to note that the FDA does have patient-focused drug development meetings for psoriasis and other conditions. Those meetings are put together for a greater understanding of the general patient perspective in clinical development.
For more information about these resources, visit this page on the FDA’s website.
Do you see decentralized clinical trials as something that will aid psoriasis patients?
Rahul: The ongoing COVID-19 pandemic definitely generates many challenges in the general conduct of clinical trials. Psoriasis studies face the same challenges.
I think many sponsors and CROs are trying to utilize technology to make clinical trial participation easier as well as allow decentralized approaches that don’t necessarily require patients to come to a clinical site and have a face-to-face visit – the way clinical trials have traditionally been done.
However, there's limits to how far a decentralized approach can work in clinical trials, given that there's often important laboratory tests that need to be drawn, as well as direct assessments by physicians, such as skin examination for conditions such as psoriasis.
For the particular studies PRA has ongoing for our work on psoriasis, we don't have a fully decentralized approach. But there are methods that we and the sponsors we work with are looking to implement. Another component of decentralized approaches involves patient diaries, which capture patient reported outcomes, patient reported symptoms, and compliance. In many of these decentralized trials, there’s already either paper patient diaries or electronic patient diaries to capture that data.
There’s still a fundamental limitation that for some of these assessments, it's often best for investigators to physically see and evaluate the patient. It’s an ongoing effort to find ways to utilize technology to still to capture adequate data, making it easier for patients to participate in trials and be less tied to the traditional model of patients coming in for a physical visit.
Rachel: I agree—there are many components of the assessments we conduct that are amenable to being decentralized. Patient-reported outcomes are easily recorded and transmitted via various technology platforms. One of the notable hurdles for a decentralized trial with a disease such as psoriasis are investigator-performed and reported assessments of measures that require an examination of the patient, such as extent of skin involvement and a description of the skin involvement. That‘s a major challenge that these psoriasis trials face for decentralization.
What are you most excited about regarding the future of psoriasis treatments? What lies ahead?
Rahul: I look forward to more individualized treatments that target specific inflammation pathways, in a more selective manner. That’s not only with psoriasis, but other inflammatory conditions and malignancy conditions. To me, that highly-individualized approach to medicine—the ability to see at a patient's individual genetic makeup, figuring out what's contributing heavily to a particular disease process, and targeting that problem—is what I’m most excited about.
Rachel: It’s certainly an exciting time. There are various therapeutics in development that definitely have the potential to advance and improve the treatment of psoriasis, as well as provide further insights into the pathogenesis of the disease. I look forward to future therapies having the potential to be more individualized, as research allows us to gain greater insight to which patients would be best suited to potentially respond or have a significant response to a particular therapy. All of these factors are grounds for optimism and enthusiasm for what lies ahead.
In the past 5 years, PRA has conducted 47 full-service clinical trials and 19 non-clinical dermatology projects. Among these projects are 27 psoriasis studies and 5 psoriatic arthritis studies. Through our Strategic Solutions Division (SSD), we have provided monitoring services for various trials in dermatology indications (such as scarring, skin lesion, skin graft, psoriasis, atopic dermatitis, skin infections, and wound healing). Approximately 30% of PRA’s operational staff members have worked on dermatology clinical trial.
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