Yunliu Chen,1,2,* Zhaoyang Wang,1,2,* Yuan Liang,1,2 Chunping Shen,1,2 Lei Jiao,1,2 Xin Xiang,1,2 Chaoyang Miao,1,2 Zigang Xu1,2 

1Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijng, People’s Republic of China; 2Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zigang Xu, Email zigangxupek@163.com

Background: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory cutaneous disease. IL-36 is a key treatment target in GPP. Spesolimab, a humanized monoclonal antibody of the IL-36 receptor, has demonstrated a good efficacy and a favorable safety profile in adults with GPP. However, data on its use in children are scarce.
Methods: We treated patients aged 4– 12 years with GPP with a single dose of spesolimab. The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score, GPPGA pustulation sub-score, Generalized Pustular Psoriasis Area and Severity Index (GPPASI), and the Japanese Dermatological Association severity index for GPP were evaluated. The levels of IL-36α, IL-36β, and IL-36γ were detected by the magnetic bead-based immunoassays, and the levels of IL-17A, IL-17C, IFN-γ, TNF, IL-6, and IL-8 were measured by the Olink proximity extension assay technology.
Results: We included five patients (four boys and one girl) with a median age was 6.9 years old (range: 4.8 to 10.6 years), and a median age of onset of 1.7 years (range: 3 months– 10 years and 5 months). After 1 week of spesolimab administration, all patients had a total GPPGA score of 0/1 and pustulation subscore of 0, all patients had a GPPASI of 50, and four patients had a GPPASI of 75. Meanwhile, plasma levels of IL-36α, IL-36β, IL-36γ, IL-17A, IL-17C, IFN-γ, TNF, IL-6, IL-8 all decreased, and those of IL-36α, IL-36β, IL-17A, IL-17C, and IL-6 were statistically significant. There was no recurrence after 2 to 8 months of treatment. No other adverse event was recorded apart from one patient who experienced an upper respiratory infection in the first week.
Conclusion: Spesolimab might be a prospective option for children aged 4 to 12 years.

Keywords: generalized pustular psoriasis, pediatrics, spesolimab, IL-36R