Spesolimab

Pustular psoriasis is a type of psoriasis, a chronic and recurrent immune-mediated multisystem disorder. Based on the characteristics and distribution of pustules, the disorder has different phenotypes, such as GPP. While the pathophysiology of psoriasis is not fully understood, some pro-inflammatory cytokines involved in innate and adaptive immune systems have been implicated as key mediators of psoriatic disease. Interleukin (IL)-36 is one of those cytokines whereby unregulated activation and expression of IL-36 - often due to IL36RN gene mutations - can result in pathological autoinflammatory responses in pustular psoriasis. IL-36 is expressed in epithelial and immune cells and has three members, IL-36α, IL-36β, and IL-36γ, that bind to a receptor complex to activate pro-inflammatory and pro-fibrotic downstream signalling pathways, such as increased expression and actions of pro-inflammatory cells and factors. The heterodimeric receptor complex IL-36R comprises an IL-1RL2 subunit - to which IL-36 binds - and an IL-1RAcP co-receptor.

The exact mechanism of action of spesolimab in managing psoriatic flares is unclear; however, it is believed to ameliorate inflammation by inhibiting IL-36 signalling. Spesolimab binds to the IL-36R receptor complex, preventing the binding of IL-36 downstream activation of receptor signalling pathways.