Practical Approaches to the Management of Plaque Psoriasis - Episode 6

Experience With Using Older Biologics to Treat Psoriasis

October 16, 2020
HCP Live

Transcript:

Mark Lebwohl, MD: What about women and child-bearing potential, or pregnant women? What’s your treatment of choice there?

Leon Kircik, MD: I think that’s easy. There is only one indicated biologic, right; TNF alpha inhibitors seems to be the only one.

Mark Lebwohl, MD: yeah.

Leon Kircik, MD: I think that’s really easy, it’s no brainer.

Mark Lebwohl, MD: Yeah. It’s the only one that doesn’t cross the placenta.

Erin Boh, MD, PhD, FAAD: I have a lot, not a lot, but I have a number of patients who are currently on biologics and then they get pregnant. And I’ve thrown this question out to the high-risk obese – do we switch them to certolizumab? Do we keep them on? And I can tell you, at least in my area, 9 out of 10 of the time they tell me, “Keep them on what they’re on, and discuss it with the patient.” Because if you look at the risks associated with just having bad psoriasis or psoriatic arthritis in pregnancy, the babies do fine but there is a tendency for low birth weight and a few other things, but not really anomalies. They think it’s more risky to switch to certolizumab as opposed to just staying on what they’re on.

I think when you have a young woman and she comes in and she goes, “I want to get pregnant in the next year, what do I do?”, certolizumab is where I go also. But if they’re already on it and they go, “Oops, I’m pregnant,” I have of late just, I don’t change them, I just keep them on it. But I said everybody – the high-risk OB – and work through it with them, and ultimately the patient and the OB and I make that decision.

Mark Lebwohl, MD: None of the drugs have been shown to be teratogenic. And in fact, I agree with what Erin said. You know there’s probably some risk to bad psoriasis that certainly in some patients outweighs any, even it’s really a theoretical concern about using biologics in these patients. Patients do fine during pregnancies, so far supports that.

Leon Kircik, MD: I think there’s a registry, isn’t there? I can’t remember the name.

Erin Boh, MD, PhD, FAAD: There is.

Mark Lebwohl, MD: There’s several.

Erin Boh, MD, PhD, FAAD: There’s several, mostly in the GI, the GIs have a very good history.

Leon Kircik, MD: Oh, yeah; yeah, yeah.

Erin Boh, MD, PhD, FAAD: And they keep them on it whether TNF or IL-12/23s, they just stay on their biologics.

Mark Lebwohl, MD: Yeah, certainly the risk of bad Crohn’s Disease is a lot worse for a pregnancy than the risk of any of the TNF blockers; or at this point, the 23 blockers that are coming out for that.

I’m going to ask James to tell us about your experience with the older biologists – TNF alpha inhibitors, ustekinumab, or the IL-17 inhibitors.

James Song, MD, FAAD: Yeah, Mark. We have several classes of biologics and I’ll start with the first ones, the TNF inhibitors. We have three (3) subcutaneous injections, one’s an infusion. And to me this is a class that has been repurposed for dermatology. And what I mean by that is, all of these drugs are actually approved for a non-dermatologic indication, right? We’re talking Crohn’s Disease, Psoriatic Arthritis, Dermatoid Arthritis. And years later it turns out it works well for the skin too. And one of the advantages of having that is we have the most amount of experience with this plaque. I mean you have literally hundreds and thousands of years, of patient year experience. And for a lot of patients and clinicians, they feel better knowing this has been on the market for a decade and we’ve been using it for a lot of patients.

The other advantage though is you have a lot of indications. Some of these conditions are comorbid in their psoriasis patients, right? If someone has psoriasis and Crohn’s Disease, it’s a no-brainer. Use a TNF [tumor necrosis factor] inhibitor such as infliximab or adalimumab or certolizumab.

This is a double-edge sword though, and that is because some of the safety concerns that we have seen with the TNF [tumor necrosis factor] inhibitors, and in particular patient populations, may not apply to our psoriasis patients, right? For example, you look at hepatosplenic T-cell lymphoma, that’s a terrible lymphoma and very rare, but we only saw it in our GI patients that were getting a higher dose of adalimumab, and they were also being on other immunosuppressive agents. But because it’s the same drug and different indications, they get all the same labeling. And I feel like sometimes it’s a hard sell for patients when they see that on the package insert.

When it comes to efficacy, you know we typically use 75 percent improvement from baseline, which I’ll refer to as PASI(?) 75. The class does pretty well, and anywhere from 50 to 80 percent of patients will get PASI(?) 75, depending on the drug and the trial.

What I found made it a little bit more difficult is when our treatment goals get more ambitious and we’re looking at maybe 90 or 100 percent clearance, this class as a whole does struggle a little bit more I would say. Let’s take it down to the next class, the IL-12/23 inhibitor. We really just have one. That’s ustekinumab. And I think to me this is a milestone because this was the first biologic where it was approved for a skin disease first, and then you had the arthritis indication second. And as far as efficacy, just as good, perhaps better than some other TNF inhibitors. And you were able to dose these patients much less often. You’re not doing it every were or every other week, but you’re doing it every 12 weeks. And if you look at a lot of studies looking at kind of drug persistence, right, how long will the patients be on the biologic before they stop their medication, this class does very, very well. And I think some of that may be because of the favorable and dosing regimen, and the fact that a lot of these patients are still coming in for their injection.

Now we mentioned that ustekinumab also had a psoriatic arthritis indication. That’s true but maybe not quite as robust for the joints as it is for skin. I’ve had a number of patients where I made that switch from a TNF inhibitor to ustekinumab, and it did flare, they do flare. And so that’s something that we need to be mindful of.

As far as the next class IL-17 inhibitors, there’s three. There’s two that block the IL-17 a-cytokine, which is the most potent cytokine for psoriasis. And then we have a receptor blocker and about all pretty much where IL-17 will bind to. And then we have one in the pipeline that’s going to be blocking both IL-17A and IL-17F.

As far as efficacy, I would say some of the highest numbers we have seen with PASI 90, PASI 100, you know, somewhere in the 70’s to 80’s or PASI 90. And over half of patients are PASI 100, so I think that has set the high water mark for a lot of drugs. And as far as speed, I would say it’s unprecedented, and we are talking in just four (4) weeks 75 percent improvement with a lot of these patients. I think the skin deal looks really good. Arthritis there looks just as good as well. I mean we have now head-to-head studies with IL-17 inhibitors, and TNF alpha antagonists look just as good, maybe numerically better. We also have studies showing that people who have failed multiple TNF agents also do quite well with an IL-17 inhibitor. And lastly it works well not only for kind of a classic psoriatic arthritis, but we have some data showing it works along the spine too, which is a distinct disease.

I think the big knock against the IL-17 inhibitors is you have to dose these patients more aggressively, and they do require more injections upfront. And then of course you have the inflammatory bowel disease risk. It’s rare but it’s a real thing, something that we have to make sure we’re mindful of when we’re using those agents.

Transcript Edited for Clarity


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