Role of IL-23 Inhibitors in the Treatment of Plaque Psoriasis


Matthew T. Reynolds, PA-C, reviews the mechanism of action of IL-23 inhibitors for the treatment of plaque psoriasis.

Jayme Heim, MSN, FNP-BC: We’re going to change focus. Matt, can you please talk about the mechanism of action of IL-23 [interleukin-23] inhibitors for the treatment of plaque psoriasis? What makes them well suited for treatment for this condition?

Matthew T. Reynolds, PA-C: The specific action of the 3 IL-23 inhibitors that we currently have—tildrakizumab, guselkumab, and risankizumab—specifically bind to and inhibit a subunit on IL-23 called P19. Now, as we evolved from the ustekinumab days and we’ve gone past blocking both the P19 and P40 subunits, we’ve learned that P19 subunit is essential in not only controlling Th17 cells and their subsequent byproducts, but also that that pathway is essential and considered almost the master inflammatory cytokine of all the psoriasis phenotypes that we see. In looking at the mechanism and how it’s better suited for treatment of this condition, we know that by binding to IL-23 with either of these products, we’re binding to a specific target that’s upstream in the pathway. We’re not downstream; we are actually upstream in the pathway. By binding upstream in the pathway, we get a little bit more long-term control, a little bit more efficacy, and higher skin clearance rates by using this pathway. Now, whichever drug you’re using, whichever product you’re using, you may have experienced this yourself in your own clinical practice, but most patients do well with either every-2-month or every-3-month dosing, and that’s just different from the other products that we have that are sometimes given every other week or every month-long term. That has a lot to do with that pathway that I talked about. The other great thing is, because you’re binding to a specific site upstream in the pathway, if the patient comes off the drug for whatever reason, say, they have to take a holiday or their insurance switches, you will notice in your clinical practice—I certainly have noticed in mine—that these patients will come off and 6 months later they’re still clear. That’s just due to the binding site. That’s due to the target and where it is in the overall psoriasis pathway. I think the other thing, too, is that when you bind to P19 on IL-23, you’re hitting a target that really is not involved in other essential components of the immune system. You’re not immune suppressed with the IL-23 class; you’re immune modulating. We see this evidence in patients that come in and their blood work is unchanged. We don’t see just global liver enzyme elevations. We don’t see global infections. We do see mild events of upper respiratory tract infections and nasopharyngitis. However, those event rates are very low. But overall, these patients do really well. Whether you’re treating a younger patient or an older patient, just the nature of the IL-23 pathway as a whole is not only a great Cq [clinical quality] for most patients, but now that we also know that the IL-23 pathway is implicated in psoriatic arthritis, we have additional coverage for those patients who have more aggressive disease, and they have joint involvement or they have signs and symptoms of psoriatic arthritis. But over time, we will elucidate that the IL-23 class is going to be the true master inflammatory cytokine of all psoriasis. I do think that the target itself is just a much better target in the overall treatment of the disease, as well as managing the specific phenotypes that we see in our practice.

Transcript edited for clarity

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