In this installment of Topical Conversations, Mark Lebwohl, MD, and Boni Elewski, MD, discuss spesolimab, the first FDA-approved treatment for generalized pustular psoriasis (GPP). Dr Elewski recounts the case of a patient who experienced a severe GPP flare after receiving systemic steroids and experienced rapid improvement after a single intravenous infusion of spesolimab 900 mg along with triamcinolone 0.1% ointment and hydrocortisone 1% cream. Spesolimab, an IL-36 receptor antagonist, initially approved for the treatment of GPP flares, has now also received an expanded subcutaneous indication for maintenance therapy, recognizing that the chronic nature of GPP requires continuous management beyond just reactive treatment for flares. This expansion was majorly based on results from the Effisayil 2 clinical trial, a 48-week clinical trial that showed that spesolimab significantly reduced the risk of GPP flares by 84%, compared with placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab subcutaneous treatment in the high-dose group (n=30).