New and Emerging Treatments for Generalized Pustular Psoriasis: Focus on IL-36 Receptor Inhibitors

Generalized Pustular Psoriasis (GPP) is a rare and severe subtype of psoriasis that significantly impacts patients’ quality of life. Until recently, no specific treatment modalities were available, and treatment for GPP followed the guidelines for the treatment of plaque psoriasis, consisting of conventional treatments, such as retinoids, methotrexate, and even biologics, which although effective in some cases, may be associated with significant side effects, necessitating more effective and safe options. The pathophysiology of Generalized Pustular Psoriasis is complex and not fully understood, but there is some overlap with the pathogenesis of Plaque Psoriasis. In GPP, the innate immune system seems to play a more significant role, with the interleukin (IL)-36 pathway being fundamentally involved. Spesolimab and imsidolimab, two recently developed therapeutic agents, target the IL-36 inflammatory pathway by binding to the IL-36 receptor (IL-36R). Both biologics have already been evaluated in phase 1 and 2 clinical trials and have shown promising results in terms of safety and efficacy. IL-36 receptor inhibitors demonstrated great efficacy and good safety profile in the management of patients with GPP, demonstrating their potential to emerge as a leading treatment option. This review aims to explore and summarize the current scientific literature on the most recently developed treatments for GPP.