Pathogenesis and Comorbidities of Plaque Psoriasis

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EP: 1.Pathogenesis and Comorbidities of Plaque Psoriasis

EP: 2.Psychosocial Impact of Plaque Psoriasis

EP: 3.Assessing the Severity of Plaque: The Need for Topical vs Systemic Therapy

EP: 4.Treatment Approaches to Plaque Psoriasis and the Importance of Topical Therapy

EP: 5.Plaque Psoriasis and Phototherapy

EP: 6.Plaque Psoriasis: TNF-α and IL-12/23 Inhibitors

EP: 7.Plaque Psoriasis: IL-17 Inhibitors

EP: 8.Plaque Psoriasis: Contraindications of IL-23 Inhibitors

EP: 9.Emerging Topical Therapy Options for Plaque Psoriasis

EP: 10.Introduction of a New Class of Agents: TYK2 Inhibitors

EP: 11.Plaque Psoriasis: POETYK PSO-1 and POETYK PSO-2 Trials

EP: 12.Plaque Psoriasis: BE READY Trial

EP: 13.Challenges in Plaque Psoriasis Treatment Therapy

EP: 14.Incorporating New Therapeutic Agents into Plaque Psoriasis Therapy

EP: 15.Parting Wisdom on Plaque Psoriasis

Linda F Stein Gold, MD: Hello and welcome to this HCPLive® Peer Exchange entitled, “Optimizing Treatment Strategies to Manage Psoriasis.” I’m Dr Linda Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit, Michigan, and I’m thrilled to be accompanied by several of my colleagues today. We have Dr Jerry Bagel, clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York. I also have Dr Leon Kircik, also clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai, and Dr Mark Lebwohl, dean for clinical therapeutics and professor of dermatology, again at the Icahn School of Medicine. Welcome to all of you, and let’s go ahead and get started. We’ll start by talking about the pathogenesis of psoriasis, and our understanding of the pathogenesis has evolved significantly over the years. With our increased understanding, we have more targeted and more effective therapies. Mark, could you start off and give us a high-level overview on the pathogenesis and just where are we today?

Mark Lebwohl, MD: Yes. There have been major breakthroughs in the understanding of the pathogenesis of psoriasis. There was a time when we thought the keratinocyte was the primary culprit. There was something wrong with the keratinocyte, that’s why cells multiplied quickly. Then when cyclosporine was developed to prevent rejection of transplanted organs, a patient with psoriasis was treated, his psoriasis cleared, and we then realized it was the immune system that was responsible. And cyclosporine of course knocks out all lymphocyte function and has many adverse effects. Slowly but surely, we were able to home in on the correct target that is responsible for psoriasis. First came TNF [tumor necrosis factor] blockers. They also suppress a somewhat larger part of the immune system, but then we realized when the IL-17 [interleukin-17] blockers came out, that IL-17 was a key target in clearing psoriasis. It clears psoriasis quickly because those IL-17 blockers knock out exactly what you want to knock out.

But step back a little, and the cell before that was the Th17 [T helper 17] cell, and it makes the IL-17 and it is upregulated by IL-23. So we now have antibodies that target IL-23, and what they do is by knocking out IL-23, the Th17 cell no longer has that signal to make IL-17, and so they start resting, quieting down, hibernating, and even dying. That’s why the IL-23 blockers get rid of not only IL-17 indirectly, but the cells that makes IL-17, so they give long remissions.

Linda F Stein Gold, MD: Thanks Mark, that was a nice overview, and it helps to simplify things a bit. Psoriasis was probably the first of our inflammatory skin diseases where we started to understand that the inflammation was more than just skin deep. Jerry, can you comment about that? I know psoriasis is associated with several comorbidities.

Jerry Bagel, MD, MS: Thank you, Linda. Yes, you led right into it. The inflammation that we get from psoriasis becomes systemic within the body. Dr Joel Gelfand, [MD, MSCE, FAAD,] revealed about 15 years ago that there’s an increased frequency of heart attacks, especially in people in their 20s, 30s, and 40s, who have psoriasis, compared with people who don’t have psoriasis. That method of “the heartbreak of psoriasis” is very true. But even though that exists, one of the more important aspects of dermatologists evaluating patients is looking for psoriatic arthritis, where up to 30% of people with psoriasis have psoriatic arthritis that can be disabling. It can result in mutilation of their joints. And because psoriasis tends to occur earlier than psoriatic arthritis, we’re at a pivotal position where we can make that diagnosis early, and with the proper treatment we have available now, prevent it from progressing.

In addition to psoriatic arthritis, which is a big deal in and of itself, we have other aspects in psoriasis, such as metabolic syndrome, which would be associated obviously with heart attacks and strokes, but also obesity and diabetes. In addition, hyperlipidemia is affiliated with psoriasis. Hypothyroidism is frequently common in psoriasis, as well as Crohn disease. There’s a group even with sleep apnea that has been associated with psoriasis. It may be related to obesity but may be related to psoriasis in itself. As we go further along and we start looking at the emotional components, there is an increase in suicidal ideation, increase in smoking, increase in alcoholism. We know that there’s an increased frequency of treatment for anxiety in people with psoriasis compared with people who don’t have psoriasis.

Linda F Stein Gold, MD: Jerry, I’m going to comment more on that because we now understand a lot about the fact that our patients with more severe psoriasis are more likely to die of a heart attack. We start to look at some of these internal manifestations that are associated with the systemic inflammation.

Thank you, Mark, Jerry, and Leon for this rich and informative discussion. Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

This transcript has been edited for clarity.