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Generalized Pustular Psoriasis: Recent Advancements, Resources, and Cytokine Considerations


Jason Hawkes, MD, MS, gives an overview of what clinicians need to know today about this rare condition.

Jason Hawkes, MD, MS, dermatologist in Sacramento, California, discussed the challenges and opportunities in managing the rare condition Generalized Pustular Psoriasis (GPP) during one of his sessions at the 2024 Fall Clinical Dermatology Conference for PAs and NPs in Scottsdale, Arizona. In an interview with Dermatology Times, he emphasized the importance of early diagnosis and treatment, highlighting the recent approval of spesolimab (Spevigo; Boehringer Ingelheim) for GPP and the need for better biomarkers to differentiate GPP from other conditions. He also stressed the importance of access to chronic therapies to prevent flares and improve patient quality of life.1

Dermatology Times: What turned your attention to GPP?

Hawkes: The focus on GPP is that we talk a lot about plaque psoriasis, which is predominantly driven by IL-23 and IL-17. When we're talking about the other variants of psoriasis, they don't always follow the same immunology and GPP is a great example of one variant of psoriasis that has a completely different cytokine profile. So rather than IL-23, or 17, we have really high levels of IL-36, which are driving the clinical phenotype characterized by the neutrophils, which are highly attracted by IL-36. So it's a very different immunology also a very different therapeutic approach.

Dermatology Times: Why is an understanding of this rare disease critical?

Hawkes: GPP is a very rare disease. So this isn't something that we're going to see nearly as frequent as diseases like plaque, psoriasis, or atopic dermatitis. But it's an emergent dermatologic condition. So these patients have a high mortality. They have a higher burden of disease, and quality of life is much lower compared to some of the chronic rashes that we manage on a daily basis. But these are patients we can't afford to miss the diagnosis. We need fast treatments, we need early interventions, they need good access to these therapies. And we have now GPP-specific treatments that can get these patients more than half better within 1 week. So that's a really important link to make. Even though we don't see this every day, we want to link IL-36 GPP...GPP-specific treatments with very fast response: we want to keep them out of the hospital or to keep them out of having these complications that come along with untreated disease.

Dermatology Times: What are the most significant GPP advancements you have seen in your career?

Hawkes: There have been 2 major discoveries in the GPP space and that both of them are related to the IL-36 cytokine, so we have an intravenous solution where spesolimab basically gives back the IL-36 receptor antagonists and shuts off IL-36 signaling. This is now approved for adults and children higher than age 12, who are at least 40 kilograms. So we have an intravenous solution here we can give them treatment that's going to treat acute flares. But the real exciting advancement is that we have a treatment in between flares. These patients have chronic disease. They have chronic relapsing symptoms, even when they're in between flares. Now we have a subcutaneous spesolimab treatment where we can give these patients maintenance in between flares, again, in adults and adolescents 12 years and older, at least 40 kilograms. And so this gives us a new GPP-specific therapy. This is very exciting to have this available when we do see these rare patients.

Dermatology Times: What are the challenges of treating GPP?

Hawkes: GPP can be challenging because it can mimic other conditions such as acute generalized exanthematous pustulosis (AGEP), which is very common to have a reaction from antibiotics, for example, or other medications. So one of the downsides to our approach to psoriasis, and even just inflammatory conditions in general, we don't really have good biomarkers to say this is definitely plaque psoriasis or pustular psoriasis or AGEP, for example, which we've managed quite differently. So when we have that research gap, the lack of biomarkers or tests to differentiate these, so we're still relying on, you know, our clinical approach. Even pathology can be very nonspecific. So that's going to be one area we need to really address. But the approach is going to be recognize it early, exclude those other conditions early, and get these patients to treatment so that we can eliminate again that that high risk course, including mortality on secondary organ failure, we want to shut this disease down as soon as possible. And then we want to help our patients have access to chronic therapies that can keep that disease under control and prevent these flares.

Dermatology Times: How can clinicians keep up-to-date on resources to learn and support their patients with GPP?

Hawkes: Because this is a rare condition, we don't have as much research as you're gonna see in other inflammatory conditions. But, you know, Boehringer Ingelheim really led the charge here with spesolimab. They're a great resource, so reach out to the sales reps, the MSLs. They've got a lot of literature here. We don't see as many publications, but you have these companies that have a vested interest in the management of these patients. And so you know, come out to other activities related to groups that are focused, such as the National Psoriasis Foundation, the NPF. They are trying to bring attention to these less common rare variants, so that you can get the up-to-date information.

Dermatology Times: What are your top clinical pearls regarding GPP treatment?

Hawkes: Two clinical pearls that I made in the lecture here at the conference was that one, we don't want to get in the habit of trying to use the same plaque psoriasis treatments for GPP. They typically don't work very well compared to blocking IL-36 cytokines. So that's one tip I mentioned. The other is that very interesting palmar plantar pustulosis, which can look a whole lot like GPP, but it's just a localized form. Very interesting, it doesn't respond to spesolimab treatment. So even though it can look like a pustular variant, like generalized disease, just localized, it doesn't respond to the same therapy. So we're still working on something that works really well for that localized variant of the hands and feet.

Transcript edited for clarity.


Hawkes J. What's new in GPP. Presented at: 2024 Fall Clinical Dermatology Conference for PAs and NPs; May 31-June 2; Scottsdale, AZ.

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