Treatment Outcomes and Management of Generalized Pustular Psoriasis with Spesolimab

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease characterized by sudden, widespread eruption (flare) of sterile pustules often with systemic symptoms. Spesolimab is a humanized anti-IL-36 monoclonal antibody approved in the US to treat GPP in adults and adolescents ≥12 years and weighing ≥40 kg as an IV dosage to treat flares and a SC dosage to treat GPP when patients are not experiencing a flare. Methods: We describe outcomes in 10 patients with GPP flare who received spesolimab at hospitals and clinics across the US. Results: The 10 patients were aged 18–92 years (6 female); all had comorbidities (e.g., hypertension, diabetes). All 10 patients had GPP flare symptoms, including pustular rash and erythema, and received spesolimab via IV infusion. Two patients received spesolimab within ≤1 week of flare symptoms, while initiation of spesolimab was delayed in 8 patients (5 patients by 3–4 weeks, 3 patients by ≥4 months). Seven patients had significant skin improvement within ≤1 week after the first IV spesolimab dose. Overall, 8 patients received a second IV spesolimab dose 7–35 days after the first dose to facilitate further skin clearance. One patient had a further flare 4 months after the second dose and required a third IV spesolimab infusion. In all patients who had failed multiple other treatments previously (e.g., topical/oral corticosteroids and off-label biologics), spesolimab improved flare symptoms with no washout period needed. Notably, improvements were observed in a patient with high BMI, and a 92-year-old patient. Patients reported benefits in quality of life (QoL), with increased confidence, mood, and ability to carry out daily activities. One patient developed a diffuse herpes simplex virus type 1 infection following infusion, attributed to either spesolimab or concurrent cyclosporine, and another went into distributive shock, which was unrelated to spesolimab treatment. No other safety issues were identified as related to spesolimab treatment. Conclusion: Access to targeted treatment is crucial to improve outcomes in patients experiencing GPP flare. These 10 cases demonstrate the safety and efficacy of spesolimab in providing rapid improvement in GPP symptoms and patient QoL in a real-world setting.