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Tralokinumab may neutralize IL-13 levels in atopic dermatitis
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Interleukin-13 may be the central cytokine in the skin of patients with atopic dermatitis, and by blocking interleukin-13 with targeted therapies it is possible to block many key disease characteristics such as skin barrier deficiency, according to research presented at European Academy of Dermatology and Venereology Congress.
“We looked at the skin transcriptome in patients with atopic dermatitis and compared that transcriptome to that of healthy control individuals and patients with psoriasis,” study researcher Stephan Weidinger, MD, of the department of dermatology and allergy at University Hospital Schleswig-Holstein in Kiel, Germany, told Healio Dermatology. “The global transcriptome is much more diverse in AD than it is in psoriasis, which fits well with our clinical experience that AD is a very heterogenous disease.”
The researchers evaluated the correlation of interleukin-13 (IL-13) expression with AD biomarkers in lesional skin samples from 27 cases with moderate to severe AD and 38 healthy controls.
In the cohort with AD, a high correlation was identified in lesional skin between gene expression levels of IL-13 and genes related to epidermal differentiation, lipid differentiation, lipid synthesis and skin barrier function along with chemokines involved in the attraction of immune cells and to pruritus’ and hyperproliferation, according to the study abstract.
“We also saw that IL-13 correlates closely with the expression of other type 2 skin markers and correlates negatively with skin barrier function, which fits with previous studies,” Weidinger said. “We added an anti-IL-13 antibody, tralokinumab, to see if we could restore the barrier of skin genes.”
Tralokinumab is a fully human immunoglobulin G4 monoclonal antibody in phase 3 development for AD that specifically neutralizes IL-13, according to Weidinger. In vitro cultures of human primary keratinocytes and dermal fibroblasts were stimulated with recombinant human IL-13 in the absence or presence of tralokinumab at a range of 0.1 nM to 100 nM, according to the abstract.
The researchers were successful in restoring the expression of all skin barrier genes.
“That is in vivo proof-of-concept that an anti-IL-13 antibody can counterbalance the negative skin barrier effects of IL-13,” Weidinger added.
IL-13 regulates the expression of several biomarkers in AD and normalized in a dose-dependent manner by tralokinumab in cultures of human keratinocytes and dermal fibroblasts, according to the abstract. – by Abigail Sutton
Reference:
Weidinger S, et al. Atopic dermatitis disease biomarkers strongly correlate with IL-13 levels, are regulated by IL-13 and are modulated by tralokinumab in vitro. Presented at: 28th European Academy of Dermatology and Venereology Congress; Oct. 9-13, 2019; Madrid.
Disclosures: Weidinger reports he is a speaker, advisory board member and/or investigator for AbbVie, Galderma, Incyte, LaRoche-Posay, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron and Sanofi-Genzyme. Please see the study for all other authors’ financial disclosures.