Real World Use of the IL‐36 Receptor Antagonist Spesolimab: A Systematic Review and Analysis

Background Spesolimab, an interleukin‐36 receptor antagonist, is approved for the treatment and prevention of generalised pustular psoriasis (GPP) flares. Its use has increasingly been reported in real‐world settings for both GPP and other inflammatory dermatoses. Objectives To systematically synthesise published real‐world evidence for spesolimab use in GPP, and other inflammatory conditions, with emphasis on patient characteristics, treatment patterns, clinical response, durability, outcome reporting, and safety. Methods PubMed, Embase, and Scopus were searched from inception through January 2026. Eligible studies reported human real‐world spesolimab use with clinical response, disease course, retreatment, relapse, and/or safety data. Randomised trials, reviews, editorials, and reports without sufficient clinical detail were excluded. Data were extracted using a standardised form and descriptively synthesised given heterogeneity in dosing, outcomes, and follow‐up. Results Eighty‐nine studies comprising 226 patients met inclusion criteria. Most reported GPP or mixed GPP cohorts (64 studies/189 patients), while 25 studies described non‐GPP or GPP‐adjacent dermatoses (37 patients), including pyoderma gangrenosum, acrodermatitis continua of Hallopeau, AGEP, hidradenitis suppurativa, and other neutrophilic or pustular conditions. In GPP or mixed GPP cohorts, clinical response was reported in 62 studies comprising 182 patients, including improvement (38 studies/ n = 151), clearance or near‐complete clearance (23 studies/ n = 30), and partial response (1 study/ n = 1). Time to initial response was reported in 53 studies comprising 157 patients and ranged from 6 h to 14 days. In non‐GPP or GPP‐adjacent dermatoses, clinical response was reported in all 25 studies comprising 37 patients, although responses varied by indication and often required repeated dosing or concomitant therapy. Safety reporting was inconsistent, and treatment‐relatedness of serious or clinically notable events could not be definitively assessed. Limitations The evidence base was dominated by case reports and small observational series with heterogeneous indications, dosing regimens, outcome definitions, follow‐up, and safety reporting, precluding meta‐analysis and limiting comparative or causal inference. Conclusions Published real‐world reports describe frequently rapid clinical improvement with spesolimab in GPP, while evidence outside GPP remains limited, heterogeneous, and largely case‐based. Prospective studies with standardised outcomes and safety reporting are needed.