Efficacy and safety of guselkumab in European patients with palmoplantar pustulosis: A multi-center, single-arm clinical trial (GAP study)

JAAD Int. 2024 Oct 2:18:69-78. doi: 10.1016/j.jdin.2024.09.001. eCollection 2025 Feb.

Abstract

Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder that affects palms and soles. Patients suffer significant pain, itching, and daily activity impairment. Guselkumab, an interleukin-23 inhibitor, has been approved for PPP treatment in Japan. However, there is no effective therapy licensed for PPP in Europe and the USA.

Objective: To explore the efficacy and safety of guselkumab in patients with moderate-to-severe PPP in the Caucasian population.

Methods: A multicenter, single-arm, phase II study involving 50 patients with moderate-to-severe PPP treated with 100 mg guselkumab subcutaneously for 24 weeks was conducted (GAP). Primary endpoint was the reduction of palmoplantar-pustulosis psoriasis area and severity index (PPPASI) at week 24 compared to baseline. Secondary endpoints included physician-assessed and patient-reported measures. Serum samples were taken for exploratory studies.

Results: The primary endpoint was met with a significant median PPPASI reduction by 59.6% at week 24 compared to baseline (P < .001). The proportions of patients achieving PPPASI-50 and PPPASI-75 at week 24 were 66.0% and 34.0%, respectively. Median dermatology life quality index dropped from 15 at baseline to 5 at week 24 (P < .001). Week 4 changes in interleukin-19 serum levels predicted week 24 clinical response.

Conclusion: Guselkumab may be a promising therapeutic option for PPP in Caucasian patients.

Keywords: IL-23; PPPASI; guselkumab; interleukin-19; multicenter trial; palmoplantar pustular psoriasis; palmoplantar pustulosis; smoking.