Safety and Efficacy of IL-23 Inhibitors in Plaque Psoriasis


Mark Lebwohl, MD: Let’s talk about safety of the IL-23 [interleukin-23] blockers compared to the other drugs that we all have. Let’s go one by one. Methotrexate and cyclosporine are straightforward, you touched on this, George, earlier.

George Han, MD, PhD: There’s no need for laboratory monitoring, we don’t need to worry about liver biopsy, things that we used to talk about. We don’t need to worry about putting a patient on a drug that they shouldn’t stay on for more than a year. So compared to cyclosporine, methotrexate, really worlds better. But when you think about the general safety of IL-23s, I’m not seeing anything pop up. The best data right now that we have in terms of longitudinal data looking at the nonmelanoma skin cancer—because it’s a small signal, right—is there with the TNF [tumor necrosis factor]-alpha inhibitors. We aren’t as of yet seeing that with ustekinumab. And there have been enough data I think where we can confidently say we don’t think that’s going to play a role. And by extension, I think the IL-23s. So compared to what has come before, there really aren’t any warts on this one.

Scott Gottlieb, MD: Everything has a little wart, right? Except with the IL-23s. Again, it seems like what’s not in the safety data is the most important part of their safety data.

Brad Glick, DO, MPH: So far for me, with risankizumab being a little bit newer and having fewer patients on it, but starting back with guselkumab and then with tildrakizumab, I would say right now I’ve had some URIs [upper respiratory infections], pretty typical. I’ve had that, and 1 urinary tract infection. These can happen by chance and are not necessarily drug related but nevertheless, other than that, at least in the trenches for me so far, I really have not seen very much. The only adverse effect or safety concern is not a safety concern. You have patients who may not respond to treatment. That’s been my biggest concern with these new generation drugs, whether it be any of the 3 IL-23 blockers.

Scott Gottlieb, MD: I want to circle back to quality of life. When I think of myself, potentially let’s say I will have to go on methotrexate, that’s a huge quality of life concern. Just by being on the drug, say your psoriasis clears, but quality of life will be impacted on a drug such as cyclosporine or particularly methotrexate and acitretin. Those have significant impacts on quality of life just being on those drugs. I think that has to be taken into consideration as well.

I’m not a big commercial or ad guy, but one of the ads that I’ll always remember was before ustekinumab was approved, in the JAAD [Journal of the American Academy of Dermatology]. They had and ad and it said “361” on one page, and you turn the page and it says, “the number of days you won’t need to think about your psoriasis.” And I think that’s huge. Not thinking about your psoriasis for all but 4 days a year, or whatever it is for guselkumab, is huge.

Mark Lebwohl, MD: And the same holds true for all the IL-23 blockers.

Scott Gottlieb, MD: Well that’s right, yes, of course.

Mark Lebwohl, MD: I think patients who get used to giving themselves injections are happy doing it. They know that the drugs make them better. You give yourself an injection every 3 months, or have it given to you in the office every 3 months so you don’t have to deal with it at all, as opposed to when you’re going on a trip and ask, “When do I dose myself? Do I have to carry this cool pack with me? Can I go on a vacation?”

Or I can actually give you the example of a patient of mine who wanted to be an US Army Ranger, and a little-known fact is that the US Army will not take psoriasis patients, and he wanted to hide the fact that he had psoriasis. And this is in the days before we had the current crop of IL-23 blockers. So my plan was to treat him with cyclosporine to clear him quickly, because he was going for his physical very soon thereafter, and make sure he didn’t get high blood pressure from the cyclosporine. Once he had his physical, we put him on ustekinumab, so that he could get it as infrequently as every 3 months because he was going to be going to places where they didn’t even have refrigeration. That’s what he did. And that actually worked well. He did make it into the Rangers and stayed there.

Transcript edited for clarity.

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