Spesolimab for the Treatment of Generalized Pustular Psoriasis Flares.

Background: Generalized pustular psoriasis (GPP) is a rare, life-threatening neutrophilic skin condition characterized by widespread sterile eruptions. Treatment approaches vary due to a lack of standardized guidelines. Interleukin-36 signaling is involved in GPP activation and disease progression. An interleukin-36 receptor monoclonal antibody, spesolimab, is a new treatment option for GPP flares. The Effisayil 1 clinical trial investigated the efficacy and safety of spesolimab, a remarkable task due to the unpredictable nature of GPP flares coupled with intrinsic trial challenges.

Methods: We searched PubMed using the terms: generalized pustular psoriasis, spesolimab, and Effisayil 1.

Clinicaltrials: gov was used to identify clinical trial data including efficacy, safety, and tolerability.

Results: In Effisayil 1, a phase II study, 53 patients with a GPP flare were enrolled: 35 patients were randomized to spesolimab and 18 to placebo. At baseline, 46% of the patients in the spesolimab group and 39% of the patients in the placebo group had a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 3; 37% and 33% of patients in each group, respectively, had a pustulation subscore 4. At the end of week 1, 19 of the patients in the spesolimab group, (54.3%) had a pustulation subscore of 0 compared to 1 patient in the placebo group (5.6%) (-49%, P<0.001).

Conclusions: The Effisayil 1 trial faced many difficulties affecting trial completion, but the results of this study provided encouraging results. Spesolimab was effective in treating GPP flares after just one week. Patient demographics and baseline characteristics did not affect the efficacy or safety profile of spesolimab. J Drugs Dermatol. 2025;24(3):242-245. doi:10.36849/JDD.8322.