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Interleukin (IL)\u201036 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL\u201036 receptor (IL\u201036R)\u2010targeting antibody, spesolimab, in IL\u201036\u2010mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL\u201036R at a binding site distinct from its agonists, IL\u201036\u03b1\/\u03b2\/\u03b3, and at least one endogenous antagonist, IL\u201036R antagonist. In\u00a0vitro and in\u00a0vivo data for spesolimab show effective inhibition of IL\u201036R\u2010mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL\u201036R\u2010mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient\u2010reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL\u201036 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL\u201036 in the human immune system and the mechanism behind IL\u201036\u2010mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need.<\/jats:p>","DOI":"10.1111\/1346-8138.17449","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:34:44Z","timestamp":1728282884000},"page":"1379-1391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Spesolimab, the first\u2010in\u2010class anti\u2010\n                    <scp>IL<\/scp>\n                    \u2010\n                    <scp>36R<\/scp>\n                    antibody: From bench to clinic"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8372-3754","authenticated-orcid":false,"given":"Akimichi","family":"Morita","sequence":"first","affiliation":[{"name":"Department of Geriatric and Environmental Dermatology Nagoya City University Graduate School of Medical Sciences  Nagoya 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