Spesolimab Use for Generalized Pustular Psoriasis Flare Prevention in Patients with Concomitant Plaque Psoriasis: Results from the Effisayil 2 Trial

Abstract

Introduction & Objectives: Generalized pustular psoriasis (GPP) is a chronic inflammatory, potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, 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 the effect of spesolimab versus placebo on Target Plaque Severity Score (TPSS) in patients with concomitant plaque psoriasis (PsO) in Effisayil 2. Materials & Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to high-dose spesolimab (loading dose 600 mg, maintenance dose 300 mg every 4 weeks), medium-dose spesolimab (loading: 600 mg, maintenance: 300 mg every 12 weeks), low-dose spesolimab (loading: 300 mg, maintenance: 150 mg every 12 weeks), or placebo for 48 weeks. One PsO lesion of ≥9 cm2 with TPSS total score ≥5 and induration sub-score ≥2 was selected by the investigator at baseline for each participant. Severity of erythema, scaling, and induration (plaque thickness) of the target lesion was assessed at baseline and subsequent visits on a 5-point scale (0, none to 4, very marked), with the summation of the 3 subscores representing the TPSS total score (0-12). Results: TPSS was measured in the 33/123 (27%) patients with PsO in the trial (9 placebo, 10 low-dose, 7 medium-dose, 7 high-dose). Mean TPSS total score was 4.2 in placebo and 4.6 in spesolimab-treated patients at baseline. By Week 4, mean TPSS remained similar in both groups (placebo, 4.3; spesolimab, 4.6). By Week 16, mean TPSS in the placebo group increased to 4.4 and decreased to 3.6 in spesolimab-treated patients. Mean TPSS total scores at Week 48 for both groups were below baseline (placebo, 3.3; spesolimab, 3.8). The number of patients with TPSS data declined in both groups over time due to GPP flare and/or early discontinuation. Conclusion: Low baseline TPSS scores observed in this subpopulation of 33 GPP patients with concomitant PsO suggest that concomitant PsO plaque characteristics in GPP are generally mild to moderate. TPSS scores remained low and consistent throughout the trial in both dosing groups and decreases in TPSS score by Week 16 (spesolimab-treated) and Week 48 (both groups) compared to baseline were observed.