Real-world use of subcutaneous spesolimab for ongoing disease control in generalized pustular psoriasis: A report of two patient cases

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, autoinflammatory skin disease characterized by sudden onset of widespread eruptions of sterile pustules, often accompanied by systemic symptoms. Patients with GPP may experience persistent signs, symptoms and disease burden between flares. Spesolimab is a humanized anti-interleukin-36 receptor monoclonal antibody approved in the US for treatment of GPP in patients aged ≥12 years old. Intravenous (IV) spesolimab is indicated for the treatment of GPP flares and subcutaneous (SC) spesolimab is indicated for treatment when patients are not experiencing a flare. We describe clinical characteristics, real-world treatment patterns, and outcomes of two adults with GPP who received SC spesolimab for ongoing disease control. Methods: Outcomes were reported for two adults with GPP who received SC spesolimab 300mg every 4 weeks at two US clinical practices. Data were collected during routine clinical practice, and included patient demographics, comorbidities, GPP presentation, treatment history, clinical outcomes, and adverse events. Changes in skin clearance were assessed using clinician-reported percentage of affected body surface area (BSA) and/or Generalized Pustular Psoriasis Physician Global Assessment (GPPGA). Results: Patients initiated SC spesolimab following control of a GPP flare. Patient 1 was a 22-year-old Hispanic female with recurrent GPP flares resulting in seven hospitalizations prior to spesolimab initiation. Initial disease involvement was localized to the neck before progressing to the trunk and extremities; worsening itch and tenderness led to the first hospitalization and confirmation of GPP diagnosis. Over 6 years, the patient received multiple therapies for GPP management, including topical corticosteroids (TCS), systemic immunosuppressants (cyclosporine, methotrexate, prednisone), and biologics (guselkumab, certolizumab, infliximab). During the most recent hospitalization for a GPP flare, the patient presented with 60% BSA involvement and subsequently received a single 900mg IV dose of spesolimab. Complete clearance occurred within 5 days, and SC spesolimab was initiated four weeks later. During over 2 years of on-going SC spesolimab, the patient reported decreased pain, complete resolution of itch, and sustained 0% BSA involvement during periods of adherence. Patient 2 was a 37-year-old White female with chronic kidney disease and a history of depression and gestational diabetes. There was no history of GPP flares or psoriasis-related diagnoses before presenting with widespread GPP disease involving 90% BSA. The patient was managed in an outpatient setting with triamcinolone and methotrexate, which cleared the flare. SC spesolimab was initiated 6 weeks later, when the patient was not experiencing an active GPP flare. GPPGA score improved from 2 at SC spesolimab initiation to 0.33 at 4 weeks, with only minor residual erythema. Patient 2 reported various concomitant therapies, including those related to GPP management (triamcinolone, roflumilast) and therapies for other conditions (bupropion, buspirone, duloxetine, estradiol). Neither patient reported adverse events during SC spesolimab treatment. Conclusion: Treatment with SC spesolimab was associated with improved and sustained disease control and favorable tolerability in two adults with GPP who had distinct clinical presentations, including complex treatment history and various comorbidities. These cases provide real-world examples of SC spesolimab use for ongoing GPP disease control.