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Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease with a considerable clinical burden. In the EffisayilTo evaluate patient-reported outcomes (PROs) of patients with GPP who were treated with intravenous (IV) spesolimab 900 mg in the Effisayil53 patients presenting with a GPP flare were randomized (2:1) to receive a single dose of IV spesolimab 900 mg or placebo and were followed for 12 weeks. Four PROs [pain visual analog scale (pain VAS); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue); Dermatology Life Quality Index (DLQI); and Psoriasis Symptom Scale (PSS)] were assessed throughout the 12-week study. Minimal clinically important differences (MCIDs) were defined. All data are reported descriptively.In patients who received spesolimab, improvements from baseline (median [Q1, Q3]) were observed in pain VAS (-21.3 [-55.3, -3.1]), FACIT-Fatigue (7.0 [1.0, 20.0]), DLQI (-2.5 [-8.0, 1.0]), and PSS (-4.0 [-7.0, 0.0]) within 1 week of treatment. These improvements were sustained over 12 weeks and corresponded to the achievement of MCIDs at Week 1, which were also sustained over 12 weeks. Patients in the placebo arm experienced improvements in PROs and achievement of MCIDs after receipt of open-label spesolimab at Week 1.Patients with a GPP flare treated with spesolimab achieved improvements in PROs by Week 1, which were sustained for 12 weeks, and achieved MCIDs as early as Week 1.