Commentary on a Clinical Trial of Spesolimab, a Humanized Anti-interleukin-36 Receptor Monoclonal Antibody, in Generalized Pustular Psoriasis

Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening autoinflammatory skin disease, mainly mediated by the interleukin (IL)-36 signaling pathway. The irregular and relapsing pattern of the skin symptoms, the GPP-associated complications, as well as the physical pain caused by the disease add burdens to patients with GPP. Currently, spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, has been approved as a GPP-specific treatment targeting IL-36 signaling. Effisayil 1, a randomized, controlled clinical trial, investigated the efficacy and safety of spesolimab in patients presenting with a GPP flare. In this commentary, we discuss the study design, endpoints, and clinical outcomes of Effisayil 1, which differed from previous clinical trials that investigated other biologic agents (adalimumab, secukinumab, brodalumab, ixekizumab, and guselkumab) in patients with GPP.