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

Abstract

IntroductionThe 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. MethodsWe conducted a double-blind, randomized controlled trial in which 26 mild-to-severe plaque psoriasis patients were randomization 3:1 to 100mg 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. ResultsThe 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 treatment. Changes in the lesional ceramide profile during treatment correlated with barrier function and target lesion severity. Non-lesional skin remained similar throughout treatment. ConclusionGuselkumab therapy restored the skin barrier in psoriasis. Concomitant correlations between skin barrier function, the ceramide profile and disease severity demonstrate their interdependency.