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IL-23 Inhibitors for Plaque Psoriasis Treatment


Andrew Blauvelt, MD, MBA, of Oregon Medical Research Center, highlights a newer class of biologics used to treat plaque psoriasis, IL-23 inhibitors, and explains how they differ from other classes of therapy.

Andrew F. Alexis, MD, MPH: Moving to a different class of biologics, the IL-23 inhibitors, the ones that are p19 subunit-specific. I'm going to turn to Dr Blauvelt for this one. Could you speak to this class of inhibitors, IL-23 specific inhibitors? How are they administered? What frequency? Talk about some of the pros and cons. Go ahead, Andy.

Andrew Blauvelt, MD, MBA: Right. Thank you, Andrew. I see the newest class of biologics as a variant on a theme or an improvement, if you will, on ustekinumab, which is an IL-12/23 blocker. The difference in these 2 types of drugs is the type of molecule that's bound by the antibody. With ustekinumab, we're targeting p40, which is a subunit of both IL-12 and IL-23. That's why we hit both of those cytokines with ustekinumab. With the newer drugs, as you mentioned Andrew, we target p19, which is a subunit that binds with p40 to create IL-23, and it's not a part of IL-12. By binding p19, we're selectively targeting IL-23.

What we see is the same kind of infrequent dosing with these new IL-23 blockers as we saw with ustekinumab, for the most part. Two of them, tildrakizumab and risankizumab, are dosed every 12 weeks, just like ustekinumab. The third, guselkumab, is dosed every 8 weeks instead of every 12 weeks. In general, I see them as more long-acting drugs, definitely compared to the other classes.

Andrew F. Alexis, MD, MPH: Great. That was very helpful. What about safety? In particular, long-term safety data for this class of drugs. April, would you like to take that one?

April W. Armstrong, MD, MPH: Yes, Andrew. I would say that, overall, when we look at the safety data for the available agents over time, we do not see an increase in the numbers of adverse events, for example, that we see in the initial parts of the trials. Overall long-term data for most of the biologics that we have is really, no news is good news. With regard to TNF inhibitors, in terms of long-term safety data, what we saw is that there's no increased risk of serious infections or internal malignancy.

There are some data showing perhaps there are increased rates of SCC [squamous cell carcinoma] with some TNF inhibitors, but one thing we need to bear in mind is that a lot of these patients who were enrolled initially in these trials were also patients who had received PUVA [psoralen and ultraviolet A] therapy. Some of the previous treatment with PUVA may have confounded some of the findings that we see. Then for IL-17 inhibitors, long-term safety data look very good. There's no increased risk in terms of serious infections or malignancies. Same for the IL-23 inhibitors.

As we follow these biologics over time, consistently what we've seen is that what we saw initially, in terms of what we understood as their safety profile, we do not see increases in rates in these medications as patients are on them for a longer period, which is reassuring.

Andrew F. Alexis, MD, MPH: It’s very reassuring indeed, and very relevant given that psoriasis is a chronic, long-term condition. Thank you for that.

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