Filling the gaps in generalized pustular psoriasis: role of IL-36R antibodies

Generalized pustular psoriasis (GPP) is a rare skin disorder that presents with flares of extensive sterile pustules. No GPP-specific treatment has been approved in the U.S. or Europe, and the lack of universal guidelines complicates the treatment of this debilitating disease. Recently, the pathophysiology of GPP has been attributed to overactivation of the interleukin-36 (IL-36) signaling pathway, due to loss-of-function mutations uncovered in the gene encoding the IL-36 receptor antagonist. The IL-36 receptor has therefore become a promising target for therapeutic intervention, with early studies of anti-IL-36R treatment, namely spesolimab and imsidolimab, demonstrating rapid inhibition of the IL-36 signaling pathway and improvement of disease symptoms. Both treatments were well tolerated with no serious adverse events reported, making anti-IL-36R treatment a promising addition to the sparse therapeutic options currently available.