Spesolimab, an anti-interleukin-36 receptor antibody, in patients with palmoplantar pustulosis: results of a phase IIa, multicenter, double-blind, randomized, placebo-controlled pilot study

Mrowietz, U. et al. (2021) Spesolimab, an anti-interleukin-36 receptor antibody, in patients with palmoplantar pustulosis: results of a phase IIa, multicenter, double-blind, randomized, placebo-controlled pilot study. Dermatology and Therapy, 11, pp. 571-585. (doi: 10.1007/s13555-021-00504-0) (PMID:33661508) (PMCID:PMC8019016)

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Abstract

Introduction: Palmoplantar pustulosis (PPP) is a chronic, inflammatory skin disease, with high disease burden, that is often refractory to treatment. There is a high unmet clinical need for the treatment of patients with PPP. The objectives of this study were to evaluate the safety and efficacy of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients with PPP. Methods: This was a phase IIa, multicenter, double-blind, randomized, placebo-controlled pilot study comparing 900 mg spesolimab (n = 19), 300 mg spesolimab (n = 19), and placebo (n = 21) administered intravenously every 4 weeks until week 12 in patients with PPP. The primary efficacy endpoint was the achievement of Palmoplantar Pustulosis Area and Severity Index 50 (PPP ASI50) at week 16, defined as achieving an ≥ 50% decrease from baseline PPP ASI. Results: At week 16, 31.6% of patients in both spesolimab dose groups achieved PPP ASI50 versus 23.8% receiving placebo (risk difference 0.078; 95% confidence interval –0.190, 0.338). Thus, the primary endpoint was not met. Spesolimab was well tolerated with no clinically relevant treatment-emergent safety signals observed. Conclusions: PPP severity declined over time in all treatment groups after the start of treatment, with a faster decline in the spesolimab arms than in the placebo arm, indicating a potential treatment effect for spesolimab. Limitations to the study included a small sample size and lower overall disease severity than expected at baseline. It is possible that the primary efficacy endpoint may have coincided with natural disease resolution in some patients. Further effects of the efficacy of spesolimab in PPP are being explored in a phase IIb trial.

Item Type:Articles
Keywords:BI 655130, IL-36, IL-36R, PPP, biomarkers, palmoplantar pustular psoriasis, palmoplantar pustulosis, randomized controlled trial, spesolimab
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burden, Professor David
Authors: Mrowietz, U., Burden, A. D., Pinter, A., Reich, K., Schäkel, K., Baum, P., Datsenko, Y., Deng, H., Padula, S. J., Thoma, C., and Bissonnette, R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Dermatology and Therapy
Publisher:Springer
ISSN:2193-8210
ISSN (Online):2190-9172
Published Online:04 March 2021
Copyright Holders:Copyright © 2021 The Author(s)
First Published:First published in Dermatology and Therapy 11: 571-585
Publisher Policy:Reproduced under a Creative Commons License

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