IL-23 Inhibitors for Treatment of Plaque Psoriasis



Mark Lebwohl, MD: Let me turn to you Erin for the next question, which is, how are the available IL-23 [interleukin-23] inhibitors for the treatment of plaque psoriasis administered, and at what frequency?

Erin Boh, MD, PhD, FAAD: All of the IL-23s, they block the p19 subunit and so they work in a similar fashion, all of them are injectable. The first is guselkumab, which is 100 mg [subcutaneous]. It’s given at week zero, week 4, and then Q [every] 8 weeks. The other 2, tildrakizumab and risankizumab, are dosed at [every] 12-week intervals.

The dosing on tildrakizumab is 100 mg at week zero, week 4, then [every] 12 weeks. And then the risankizumab is a 150-mg loading dose at week zero, and week 4. And then [every] 12 weeks.

Generally, guselkumab is given in the office, but I will tell you, in many of my injectable-experienced patients, they inject it at home, and they have no issues with it, but that usually is administered in the office. Whereas risankizumab, I have them self-inject. And the tildrakizumab is usually self-administered as well. But that can be given as IV [intravenously].

Mark Lebwohl, MD: I believe the risankizumab comes in 75 mg.

Erin Boh, MD, PhD, FAAD: Correct, so it’s 2 shots, but it is 150-mg dosing.

Mark Lebwohl, MD: Leon, do you want to tell us about the long-term safety for the available agents?

Leon Kircik, MD: I think I’m going to concentrate on the new ones, IL-17s, IL-23s. We did talk quite a bit about the TNF [tumor necrosis factor] alpha inhibitors already. When you look at the safety and long-term safety, let’s start from the IL-17 drug, which is the first one, ustekinumab. We have 5-year long-term safety data. We do have as well with the ixekizumab, 5-year data now. I don’t believe we have 5-year data from the IL-23s yet, they come later on, but there are 4-year data. And all those when you look at them, most of the signals are very comparable to the placebo-controlled period times.

Most of the signals in psoriasis and the psoriatic arthritis population are similar and comparable. I think those are very safe drugs. As I mentioned, their package insert is 15 to 19 pages compared to 100 pages. I was looking, thinking probably the topical steroids have a bigger package insert than those new biologics. And there’s no box warning, there is no blood monitoring requirement with any of those except with the TB [tuberculosis] in the beginning, before you start you have to have a negative TB, which is the standard.

I feel that those new biologics, both the IL-17 and 23s, are very safe drugs. As long as we know the contraindication in the IL-17 category, right, it’s the IBD [inflammatory bowel disease]. But also, some people, they get very concerned when they see the fungal infection or the Candida. The way I look at it, it’s expected because IL-17 protects us against those. When you suppress it a little bit, you’re going to see it; actually in my mind you know that the drug is working.

Ironically, one of the IL-23s, I think tildrakizumab, has a couple of fungal infections and Candida. And in my mind, you know that it’s getting and suppressing IL-17, that’s why you’re getting it, right? It happens a little bit later, but it does happen eventually. So those are expected, and I always say, “Look, I’m a dermatologist, I know how to treat fungal infections and Candida. I’m not dealing with lymphoma.” I feel very comfortable and safe with the new biologics, both IL-23, and IL-17s.

Mark Lebwohl, MD: Yes, I will say people born deficient in IL-17 get yeast infections. They don’t get more cancers, they don’t get more heart attacks. They don’t get other bad things, they get yeast infections. And to me also, if you develop yeast infections, it shows that they’re behaving like those IL-17 deficient patients.

Interestingly also, the rate of yeast infections in the first year or so is about 5%. I think with the IL-17 blockers, maybe a little lower. The new one, which is more effective, bimekizumab, it’s approaching 15% in their larger trials. So again, to me it’s more effective because it’s creating better IL-17 blockade.

Erin Boh, MD, PhD, FAAD: In defense of the anti-TNFs and their safety profile, I think if we look at the data—again, the IL-17/23s, I’m not arguing, they’re faster, they [lead to] better PASIs [Psoriasis Area and Severity Index scores] in general—but there are going to be patients who need the TNFs. And if you look at the data, we have no new safety signals, no new contraindications for over 15 to 18 years. So that tells me that, yes, there is some baggage with the anti-TNFs that were known very early on. But there are patients who would benefit from it, especially like your cardiovascular patients. Patients who’ve had MIs [myocardial infarctions]. My cardiologists want me to put them back on a TNF, they don’t want me to change them.

So I can say looking at the data, there are no new safety signals for over 15, 18 years after they’ve been out. For certain populations I think this is very good drug to use when appropriately prescribed and given to the right population. I think even though there is longer PI [prescribing information], not too many of my patients read the PI, but we haven’t seen any new things come up that we have to be worried about. We know how to manage those adverse effects. I think there’s still a place for them, and they’re still very safe.

Leon Kircik, MD: There’s a level of comfort because we’ve been using these for 20 years.

James Song, MD, FAAD: I would agree with that, Erin. I think the IL-17 and the IL-23 inhibitor safety looks great, but sometimes rare events, the medicine needs to be out longer before you detect something. Even with ustekinumab, how long did it take before there were reports of reversible posterior encephalopathy syndrome or noninfectious pneumonia? These take years, if not decades. So everything looks good so far, but I think we still need some more long-term data for this class.

Transcript Edited for Clarity

Related Videos
© 2024 MJH Life Sciences

All rights reserved.