Guselkumab treatment normalizes the stratum corneum ceramide profile and alleviates barrier dysfunction in psoriasis: results of a randomized controlled trial.

Autor:	Rousel J; Centre for Human Drug Research, Leiden, The Netherlands; Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., Mergen C; Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., Bergmans ME; Centre for Human Drug Research, Leiden, The Netherlands; Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands., Bruijnincx LJ; Centre for Human Drug Research, Leiden, The Netherlands., de Kam ML; Centre for Human Drug Research, Leiden, The Netherlands., Klarenbeek NB; Centre for Human Drug Research, Leiden, The Netherlands., Niemeyer-van der Kolk T; Centre for Human Drug Research, Leiden, The Netherlands., van Doorn MBA; Centre for Human Drug Research, Leiden, The Netherlands; Department of Dermatology, Erasmus Medical Centre, Rotterdam, The Netherlands., Bouwstra JA; Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., Rissmann R; Centre for Human Drug Research, Leiden, The Netherlands; Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: rrissmann@chdr.nl.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Aug; Vol. 65 (8), pp. 100591. Date of Electronic Publication: 2024 Jul 09.
DOI:	10.1016/j.jlr.2024.100591
Abstrakt:	The epidermal inflammation associated with psoriasis drives skin barrier perturbations. The skin barrier is primarily located in stratum corneum (SC). Its function depends on the SC lipid matrix of which ceramides constitute important components. Changes in the ceramide profile directly correlate to barrier function. In this study, we characterized the dynamics of the barrier function and ceramide profile of psoriatic skin during anti-Interleukin-23 therapy with guselkumab. We conducted a double-blind, randomized controlled trial in which 26 mild-to-severe plaque psoriasis patients were randomization 3:1-100 mg guselkumab or placebo for 16 weeks and barrier dynamics monitored throughout. Barrier function was measured by trans-epidermal water loss measurements. Untargeted ceramide profiling was performed using liquid chromatography-mass spectrometry after SC was harvested using tape-stripping. The barrier function and ceramide profile of lesional skin normalized to that of controls during treatment with guselkumab, but not placebo. This resulted in significant differences compared to placebo at the end of the treatment. Changes in the lesional ceramide profile during treatment correlated with barrier function and target lesion severity. Nonlesional skin remained similar throughout treatment. Guselkumab therapy restored the skin barrier in psoriasis. Concomitant correlations between skin barrier function, the ceramide profile, and disease severity demonstrate their interdependency. Competing Interests: Conflict of interest Dr van Doorn has received consulting fees or honorarium from Novartis, AbbVie, Pfizer, LEO pharma, Sanofi, Lilly, Janssen, and Celgene and grant and payment for lectures including service on speakers bureaus from Novartis, Sanofi, and Janssen outside the submitted work. The other authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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