Skin Barrier Restored Among Patients with Psoriasis Treated with Guselkumab

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Guselkumab treatment may restore the skin barrier of patients with psoriasis, according to recent findings, with disease severity and barrier function corresponding with patients’ lesional ceramide profile during their course of treatment.¹

This new research, led by Jannik Rousel, from the Centre for Human Drug Research in the Netherlands, was conducted with the purpose of characterizing different elements of psoriatic skin’s barrier function and ceramide profile while being treated with the anti-interleukin (IL)-23 drug known as guselkumab.

To address this topic, Rousel et al. conducted a double-blind, randomized controlled study. They noted that despite prior data indicating that lesional psoriasis leads to decreased barrier function and changes in ceramide composition, integrating these conclusions with disease severity measures had largely not taken place.^2,3

“Therefore, we set out to investigate skin barrier dynamics in psoriasis by performing a randomized, placebo-controlled trial using guselkumab therapy in a cohort of 26 patients over 16 weeks of treatment,” Rousel and colleagues wrote.¹

Background and Design

The investigators' study, known as SKINERGY-PP, took the form of an exploratory, double-blinded, cingle-centered, placebo-controlled randomized trial. They conducted their research from September 2020 - January 2023, with their work being done at the Centre for Human Drug Research in the Netherlands.

This trial included individuals who were diagnosed with plaque psoriasis and were not undergoing any form of active treatment. They would also not have completed an appropriate wash-out period, would have had at least a single active, sufficiently-sized lesion for the purposes of sampling, and would have a minimum severity score of 6 or more.

Participants placed in the control group who were without dermatological conditions were matched to those in the patient cohort for age, sex, and tape-stripping location. Over the course of their research, the investigators did not allow subjects to utilize any topicals or other forms of medication on their psoriatic lesions which had been designated for the study’s assessment.

In total, the research team had recruited 26 individuals who were then randomized in a 3:1 ratio to be given a placebo or a subcutaneous injection of guselkumab 100 mg at the 0, 4, and 12-week marks. Severity was assessed by the team through an evaluation of participants’ Psoriasis Area and Severity Index (PASI) and lesion severity scores (LSS) of target lesions.

The investigators assessed the latter by a grading of subjects’ scaling, erythema, and induration using a 5-point scale. They would then add these scores together.

The research team evaluated subjects’ barrier function through the use of trans-epidermal water loss measurements. They performed untargeted ceramide profiling through the use of liquid chromatography-mass spectrometry following a harvesting of the stratum corneum using tape-stripping.

Findings

In total among the 26 subjects with psoriasis and 10 healthy controls, the investigators concluded that guselkumab therapy had led to a return to normal barrier function and ceramide profile levels in subjects’ lesional skin. The normal levels were similar to those of the healthy control group, a shift which was not noted among those given a placebo.

As a result, the research team determined that major differences had been found between the guselkumab and placebo arms of the study by the treatment period’s conclusion. The team also noted improvements in participants’ ceramide profiles of their lesional skin while subjects had been treated with guselkumab.

These notable improvements were linked to enhancements in subjects’ skin barrier function and to diminished severity of their target lesions. Contrasting with these findings, the investigators noted that subjects’ non-lesional skin indicated no major shifts throughout the course of treatment.

“Correlations between the ceramide profile and barrier function during the effective clinical response towards guselkumab, but not placebo, underline their interdependency and establishes their relationship with disease severity,” they wrote. “Ceramide profiling might represent a suitable biomarker for treatment monitoring.”

References

1. ^{Rousel J, Mergen C, Bergmans ME, Bruijnincx LJ, de Kam ML, Klarenbeek NB, Niemeyer-van der Kolk T, van Doorn MBA, Bouwstra JA, Rissmann R, on behalf of the NextGeneration ImmunoDermatology Consortium (NGID), Guselkumab treatment normalizes the stratum corneum ceramide profile and alleviates barrier dysfunction in psoriasis: results of a randomized controlled trial, Journal of Lipid Research (2024), doi: https://doi.org/10.1016/j.jlr.2024.100591.}
2. ^{Kim B.K, et al. Decrease of ceramides with long-chain fatty acids in psoriasis: Possible inhibitory effect of interferon gamma on chain elongation. Exp Dermatol. 2022; 31: 122-132}
3. ^{Uchino T, et al. Comparative analysis of intercellular lipid organization and composition between psoriatic and healthy stratum corneum. Chem Phys Lipids. 2023; 254.}