Advances in the Management of Plaque Psoriasis - Episode 8
Mark Lebwohl, MD: What about the IL-17 [interleukin-17] agents, which are new? Brad?
Brad Glick, DO, MPH: Highly effective agents. To George’s point before about TNF [tumor necrosis factor] inhibitors, Remicade infusions, despite being chimeric and being antibodies and what have you, here we have these interleukin-17 blockers that can get patients to PASI [Psoriasis Area and Severity Index] 75 in a very short period. That’s really one of the unique components of blocking interleukin-17 in my mind. And I have a ton of patients on all 3 of the IL-17 blockers, and I enjoy having them in my practice. I think it’s a challenge, however. And again, back to the inflammatory bowel disease part, and while I don’t think it’s a part of every one of our patients with psoriasis, it’s certainly an important part of the comorbid discussion. I find those agents highly effective. They work very quickly if we need to get someone better faster, we don’t really have to put them on cyclosporine, which does impart a much higher safety concern. And that’s really been my greatest appreciation.
Mark Lebwohl, MD: Some of them are even faster than cyclosporine. When you look at the time to achieve PASI 50, which we’ve published, at least 2, if not 3, of the IL-17s do it faster than cyclosporine, which takes about 3 weeks.
Brad Glick, DO, MPH: Yes, it’s in the first 2 weeks, right? The first 2 weeks.
Mark Lebwohl, MD: Yes, that’s right, 1.8 weeks for brodalumab and 1.9 weeks for ixekizumab, and secukinumab is a little bit after that.
George Han, MD, PhD: What I tell people is if I have a patient coming in who’s getting married in a week and they need to clear their psoriasis, IL-17 is a good choice. But they should not procrastinate on everything in their marriage like that or else it’s not headed anywhere good. But what’s interesting I think about the IL-17 class is that this agent has really taught us about pathophysiology. Because when you start to look at all of the inflammatory bowel disease, that was an unexpected occurrence, right? That was actually from a clinical trial design to prove that it works for it. And then we start to realize, well, there’s this subset of regulatory IL-17 cells in the gut that help to act in a regulatory fashion.
And when you block those, you get increased microbial penetration, increased intestinal inflammation, and that’s where we think that’s coming from. And it’s interesting. When you just look at it from an over-the-top perspective, IL-23 works through the IL-17 pathway, but really it doesn’t affect those regulatory cells, only pathogenic ones. So we’ve really learned a lot about the pathophysiologic mechanisms of psoriasis through these agents, which is cool, I think.
Brad Glick, DO, MPH: I agree completely. And one of the things with inflammatory bowel disease is that some of our gastroenterology colleagues, particularly those who are interested in immunologies, would say that when we’re blunting certain cytokines, specifically along that Th-17 pathway, we’re downregulating other cytokines, too. Some of those cytokines like interleukin-22 actually may be responsible for colonic mucosal preservation. And we have learned a lot with these unique mechanisms of action with these biologic therapies.
Transcript edited for clarity.