Role of Topical Treatments in GPP Treatment

Mark G. Lebwohl, MD, explores the role of topical treatments such as corticosteroids and tacrolimus in treating generalized pustular psoriasis (GPP) and important safety considerations.

Ryan Haumschild, PharmD, MS, MBA: I want to turn to Dr Lebwohl. I think we’ve given a great overview of treatments, but there’s also the role of topical treatments that have to do with corticosteroids or tacrolimus in treating generalized pustular psoriasis [GPP]. Dr Lebwohl, when we think about these topical treatments, do they offer just primarily symptom relief or disease modification?

Mark G. Lebwohl, MD: Primarily symptom relief. I’ll tell you about some of the hazards too, but I will say, before we had spesolimab, even in an era where we had biologics and we had methotrexate or cyclosporin, the patients are so uncomfortable; they’re covered in pus. Things like whirlpool baths and topical steroids are widely used. If I had my druthers, I would use one of the topical steroids that is hardly absorbed, or fluticasone, which is a soft molecule that’s broken down so that you don’t have to worry about the patient becoming cushingoid. What’s most often used is triamcinolone acetonide because it comes in large tubs, and the patients often need it on large surface areas of their skin. They might be covered in wet sheets to debride some of that skin and then treated with triamcinolone acetonide. I will say that was traditional a few years ago. We’ve been doing the spesolimab trial for a few years, so we’ve had that as an option, and I must say a much better option. Again, largely for [the patient’s] comfort.

I will point out also that with the amount of steroid topically that you have to put on a patient’s body and the amount that gets absorbed, you might as well be giving them prednisone. There was an old study done, in 1969 by [Terence] Ryan and [Harvey] Baker, and they compared a folic acid antagonist similar to methotrexate, to systemic steroids. Nearly a quarter of the patients treated with systemic steroids died, so not a good way to go. There are reports of patients covered in super potent topical steroids for psoriasis, not pustular psoriasis. When that was stopped, the patients broke out in generalized pustular psoriasis, as if they had gotten prednisone. There’s a hazard to using topical steroids as well. There’s also one, it’s almost humorous, but a patient who developed pustular psoriasis after ingesting a super potent topical steroid, eating a tube. It’s really published, but I can’t quite understand what was going on there. Maybe it was a cream and she thought it was like something you put on bread, but that’s a true story.

Ryan Haumschild, PharmD, MS, MBA: There’s a difference between the cream and Brie cheese, just making sure we go through that with patients, just another reminder. Something you talked about is the safety considerations. I think when we’re treating patients with GPP, there are important safety considerations, especially when we think about things like the long-term impact of steroids and withdrawal. Can you tell us a little about those safety considerations around the different treatments for GPP, and things that clinicians and payers should be aware of?

Mark G. Lebwohl, MD: First of all, the systemic steroids should be off the table. I told you that nearly a quarter of the patients died. Even [Erin] Boh’s, [MD,] patient, who I described to you, had been put on systemic steroids, and not because of a bad reason. They couldn’t do anything else, and she had to fight to get spesolimab. To me, systemic steroids should be off the table for these patients. They have so many adverse effects. With methotrexate, we always worry about the liver and bone marrow. With cyclosporine, we worry about the kidneys. Long term we worry about lymphomas and skin cancers. The biologics are fairly benign. The TNF [tumor necrosis factor] blockers have boxed warnings for infection and malignancy. In particular, I say infliximab, which is one of the most potent biologics we have, has been used, but there are cases of sepsis, and now you’re giving those patients a strongly immunosuppressive drug. That of course is a deadly combination. The IL-17 [interleukin-17] and IL-23 blockers are much more benign. They don’t have boxed warnings, so it’s probably not much chance that you’ll harm the patient other than the fact that you’re not giving them the treatment. I am also very wary of combining immunosuppressive drugs.

As Erin said, and as my colleagues have noticed, and I have too, often we don’t have a choice. The patients come to us. Somebody with good intentions put them on one of the drugs they could get quickly and easily because they were worried about them. Now we’ve got to add spesolimab. You’ve got something that blocks IL-17 with something that blocks IL-36. Is that going to predispose the patient to sepsis? Maybe, but hopefully not. So far, we’ve been OK with that. I’ve done that in my practice as well just because there was no other option. The drugs that do not affect the immune system are retinoids. I think those are safely combined with any of the biologics.

Ryan Haumschild, PharmD, MS, MBA: We’ve talked a lot about spesolimab, and we know it’s a new treatment. It’s kind of changing the way we approach patients with GPP. You talked about this a bit earlier, but Dr Lebwohl, can you maybe go through it one more time with us? What is spesolimab? How does it work? How is it unique compared to the IL-17s and 23s that we’re used to using? Are there any important patient considerations for spesolimab when we’re treating an acute indication of GPP?

Mark G. Lebwohl, MD: The other biologics like IL-17 are measurable. You can measure IL-17 in the skin of patients with GPP, and clearly, in the pathogenesis of GPP, IL-17 is there, and it has some role. Undoubtedly IL-23 does as well. We’re hitting little parts, but we can hit the kingmaker, the one that’s really causing the disease, which is IL-36. Spesolimab blocks the receptor; it’s the IL-36 hitting the receptor that triggers generalized pustular psoriasis. It can’t hit the receptor when you have spesolimab blocking that receptor.

Ryan Haumschild, PharmD, MS, MBA: Excellent. It sounds like there’s an effective pathogenesis, and we’re able to attack it now with newer treatments, but we know that sometimes the control and access to those is something that we’ve got to be considerate of. I like how you said earlier, your No. 1 job is to stay up to date on literature, but also advocate for your patients.

Transcript edited for clarity.

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