Measuring GPPGA, Pain, Symptom, and Quality of Life Index Scores in Untreated Generalized Pustular Psoriasis: Results from the Placebo Group of the Effisayil-2 Trial

Abstract

Introduction & Objectives: Generalized pustular psoriasis (GPP) is a chronic inflammatory, and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab is approved to treat GPP flares in adults. Effisayil 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report on the underlying disease burden of untreated GPP by longitudinally analyzing patients in the placebo group who did not experience a GPP flare. Materials & Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. Patients were assessed for measures of chronic disease burden through the use of Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) Total Score, Pain Visual Analog Scale (VAS), and Psoriasis Symptom Scale (PSS) at baseline and at 4-week intervals during the trial, and Dermatology Quality of Life Index (DLQI) at baseline and weeks 4, 8, 12, 24, 36, and 48. Results: 16/31 placebo-treated patients experienced a GPP flare over the 48-week observational period of the trial, defined as an increase in GPPPGA score by ≥2 from baseline and the pustular component of GPPPGA ≥2. Of the remaining (“non-flaring”) 15 patients, 40% (6/15) had at least one GPPPGA Total Score value of 2 (skin not clear or almost clear); 4/6 reported such score at ≥4 visits. Pain scores ranged from 0 to 92.47, with 47% (7/15) and 20% (3/15) of patients having at least one “moderate” and “severe” VAS score over 48 weeks, respectively. Most of the 7 patients’ pain scores fluctuated with episodic peaks and valleys. 47% (7/15) and 13% (2/15) of patients had at least one “moderate” and “severe” PSS score, respectively. “Moderate” and “very large” effect on quality of life was reported, at least once, in 67% (10/15) and 40% (6/15) of patients, respectively. Conclusion: Acute flare was reported in more than 50% (16/31) of patients in the placebo group over 48 weeks. Despite not meeting the trial’s definition of GPP flare, most of the 15 “non-flaring” placebo-treated patients showed clear evidence of underlying GPP disease activity – nearly half did not have “clear” or “almost clear” skin and had moderate pain and symptoms; a small subset reported severe pain and symptoms. Majority of patients experienced a moderate to very large impact on quality of life over the 48 weeks. These findings suggest that untreated GPP negatively affects patients even in the absence of acute flare events.