GPP Awareness Day: Flare Triggers and IL-36 Targeted Therapy With Spesolimab

“What are the common triggers of GPP flares? Well, it's everyone's favorite treatment: systemic corticosteroids. Coming off of those has been a leading cause. Infections, pregnancy, and rapid withdrawal of other drugs. Of course, there are tons of case reports of that. Then, like all things somewhat related to psoriasis, stress. These are some of the common causes,” said Aaron Farberg, MD, in a recent interview.

Farberg, a double-board-certified dermatologist and Mohs surgeon and the chief medical officer at Bare Dermatology in Dallas, Texas, detailed how spesolimab-sbzo (Spevigo; LEO Pharma & Boehringer Ingelheim) has changed management of generalized pustular psoriasis (GPP) in recognition of GPP Awareness Day, August 13. Farberg, who leads the dermatology residency program at Lake Granbury Medical Center, also addressed the value of a multidisciplinary approach to care.

Common Triggers of GPP Flares

Systemic corticosteroid withdrawal remains a leading trigger of GPP flares, according to Farberg, who described it as one of the most consistently reported causes. Infections, pregnancy, rapid withdrawal of other systemic drugs, and stress also contribute, and he noted case reports have documented each repeatedly.¹ Some GPP cases stem from underlying genetic mutations while others arise de novo without an identifiable cause, reinforcing the need for a full clinical history to confirm the diagnosis.

"It's always important to consider a full history when you're seeing these patients in your clinic to really determine the actual diagnosis, if it is GPP," Farberg said.

IL-36 Targeted Therapy With Spesolimab

Spesolimab is available as an intravenous infusion for acute GPP flares, and as a subcutaneous injection to prevent flares in patients with chronic disease, Farberg said.² The drug targets IL-36, which he described as the most active pathway in the disease and the mechanism with the greatest treatment impact. Farberg compared its arrival to the first biologic approved for plaque psoriasis, noting additional agents targeting the inflammatory cascade further downstream are in development, though none are yet commercially available.

"Spevigo is a knock-it-out-of-the-park win when you have to treat GPP," Farberg said.

Multidisciplinary Care and Switching From Other Biologics

Farberg described GPP management as requiring collaboration with colleagues in urgent care and the emergency department to keep patients systemically stable before and during treatment. He noted many patients with GPP are already on other psoriasis biologics targeting IL-17 or IL-23, often because those agents were easier to access or already on hand, but said they are not the ideal treatment for GPP given the disease's distinct IL-36-driven mechanism. Farberg recommended switching patients to spesolimab-sbzo once GPP is confirmed, to optimize both flare prevention and treatment of active flares.

"It's worthwhile ensuring that these patients can get on the right drug, switching them to the right drug to optimize their care," Farberg said.

Farberg said ensuring patients with GPP receive spesolimab, rather than remaining on a suboptimal psoriasis biologic, is central to optimizing their long-term care.

References

1. Choon SE, Navarini AA, Pinter A. Clinical course and characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23(suppl 1):21-29. doi:10.1007/s40257-021-00654-z
2. Spevigo approved for expanded indications in China and the US. News release. Boehringer Ingelheim. March 19, 2024. Accessed August 13, 2026. https://www.boehringer-ingelheim.com/us/spevigo-approved-expanded-indications-china-and-us