Spesolimab, an interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis

Generalized pustular psoriasis (GPP) is a rare cutaneous and systemic inflammatory disease which is characterized by flares of widespread painful pustulation of the skin, often associated with fever and elevated inflammatory markers. Although it has historically been regarded as a severe variant of plaque psoriasis, genetic and immunological developments over the past decade have revealed that it is a distinct auto-inflammatory entity, in which over-activity of the interleukin-36 signaling pathway is fundamental. Treatments targeting the IL-36 pathway are under investigation, and in 2022 spesolimab, a monoclonal antibody against the IL-36 receptor, was licensed for treating flares of GPP.

In this review I discuss the epidemiology, clinical features, genetics, patho-mechanisms, and current treatment options for GPP. I describe the results of clinical trials that led to the licensing of spesolimab for flares of GPP.

The marked efficacy of spesolimab in GPP opens a new era of highly effective, scientifically-rational, and evidence-based treatment for this orphan disease, and has implications for other diseases in which interleukin 36 signaling is involved.