Review of Current and Novel Treatment Pathways to Manage Plaque Psoriasis - Episode 7

Plaque Psoriasis: IL-17 Inhibitors

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Dr Kircik discusses the mechanisms of action involving IL-17 inhibitors when using them as a first-line therapy for plaque psoriasis.

Linda F. Stein Gold, MD: Leon, let’s talk about IL-17s. What’s their role? Is it first line?

Leon H. Kircik, MD:IL-17s are great drugs for several reasons. No. 1, as Mark mentioned, is their safety profile. I feel very comfortable. If you look at their package insert, it’s 19 pages vs taking a TNF [tumor necrosis factor]–alpha inhibitor package, which is full of [black] box warnings and is 121 pages. That’s simple, right? Their efficacy is great. Their onset of action is the fastest. Mark did a great job when he explained the pathophysiology of how the IL-23 works by inhibiting the Th17 [T-helper 17] cells; that takes awhile to kick in. There’s no reason not to start anybody on IL-17, except people with inflammatory bowel disease history. Other than that, I can’t think of anybody I wouldn’t start on IL-17, because the onset of action is fast.

Of course, I’m not mentioning brodalumab and the package that comes with it, but secukinumab and ustekinumab have a fast onset of action and are safe. The only adverse effect you have to worry about is candida, or fungal infection. We’re in the dermatology business. We know how to treat candida, or fungal infection, right? I’m not going to worry about lymphoma, leukemia, CHF [congestive heart failure], or hepatitis B. I don’t want to deal with those things, but I can deal with the candida. In my mind, those are great contributions to the armamentarium for psoriasis treatment.

Linda F. Stein Gold, MD: Jerry, with the IL-17s, have you treated anybody with inflammatory bowel disease with an IL-17, or is it a no-go for you?

Jerry Bagel, MD, MS:No-go.

Linda F. Stein Gold, MD: Mark?

Mark Lebwohl, MD:Even though the risk is small and it’s been overinflated, our guests are neurologists who have been at the forefront of describing this and will not allow us to use an IL-17 blocker.

Linda F. Stein Gold, MD: Has anybody seen the development of inflammatory bowel disease while a patient was on an IL-17?

Mark Lebwohl, MD:Yes, we’ve had about 10 cases.

Leon H. Kircik, MD:Ustekinumab is indicated for both. One thing I did not mention with IL-17s is that they work well for psoriatic arthritis, so you’re kill 2 birds with 1 stone. I don’t even have to worry that somebody is going to develop psoriatic arthritis because I’m treating both.

Linda F. Stein Gold, MD: And what about brodalumab? Is there a role for this?

Leon H. Kircik, MD:It’s 1 of the best in terms of efficacy. It does kick in fast, but you have to worry about depression. Even though we know it’s not the drug but the disease, we have to deal with that label. People say, “You’re dealing with isotretinoin, and it’s the same thing,” but we don’t have a replacement for isotretinoin. For the IL-17 class we have other options.

Linda F. Stein Gold, MD: Mark, you were involved in the clinical trials, and you have some experience with depression.

Mark Lebwohl, MD:Yes. We have a lot of patients on brodalumab. It works when everything else fails, and that means every other drug. We’ve had dramatic successes with it. That may change with bimekizumab when it comes up because it’s a highly effective drug, but for now brodalumab is the 1 that works when others don’t. It’s the fastest drug we have by far. When I have a patient coming to me and they have to be clear for something in a couple of weeks, the drug that’s most likely to do that is brodalumab. We have a great experience with it. There hasn’t been a single suicide in the several years it’s been on the market either in the United States or abroad, where they don’t have the REMS [Risk Evaluation and Mitigation Strategy] program for it.

If you go back and look at the label for the cases where they committed suicide, when it got that REMS program, I would have done what the FDA did because there was a signal that they couldn’t explain. But when you look at the cases, 1 guy was going to jail, another guy was a drug abuser and alcoholic who overdosed and didn’t leave a note. One guy was severely depressed before and ended up moving. The last 1 was the saddest 1. It was a guy whose entire income came from psoriasis disability. He achieved PASI 100 [100% reduction in the Psoriasis Area and Severity Index], and he didn’t have a source of income and committed suicide. They’re sad stories, but there hasn’t been 1 since.

Linda F. Stein Gold, MD: Thank you, Mark, Jerry, and Leon for this rich and informative discussion. Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box.

This transcript has been edited for clarity.