Abstract
INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening form of psoriasis, characterized by widespread sterile pustules and systemic symptoms. While the pathogenesis remains incompletely understood, the interleukin 36 (IL-36) pathway has emerged as a key contributor. Spesolimab, a humanized monoclonal antibody targeting the IL-36 receptor, has shown rapid and marked clinical improvement in patients during acute GPP flares. CASE PRESENTATION: We report three cases of GPP flares treated with spesolimab in Denmark, administered prior to its commercial availability through a compassionate use program. All patients presented with severe GPP and were assessed using the Physician's Global Assessment for Generalized Pustular Psoriasis. Treatment with spesolimab resulted in rapid improvement across all cases. CONCLUSION: These real-world observations support the clinical efficacy of spesolimab for managing acute GPP flares and demonstrate its potential as a therapeutic option in severe cases, even before commercial access.