Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years. - Université de Lille Accéder directement au contenu
Article Dans Une Revue Allergy Année : 2024

Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years.

Emma Guttman-Yassky
  • Fonction : Auteur
Kenji Kabashima
  • Fonction : Auteur
Walter K. Nahm
  • Fonction : Auteur
Sylvia Pauser
  • Fonction : Auteur
Joel Correa da Rosa
  • Fonction : Auteur
Britta Cathrina Martel
  • Fonction : Auteur
Daniel Elenius Madsen
  • Fonction : Auteur
Mads Røpke
  • Fonction : Auteur
Petra Arlert
  • Fonction : Auteur
Louise Steffensen
  • Fonction : Auteur
Andrew Blauvelt
  • Fonction : Auteur
Kristian Reich
  • Fonction : Auteur

Résumé

Background Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)-13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2-year impacts of IL-13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate-to-severe AD. Methods Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long-term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. Results Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL-37, and S100A8) toward non-lesional expression. Conclusion Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non-lesional levels, further highlighting the key role of IL-13 in the pathogenesis of AD.
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hal-04679825 , version 1 (28-08-2024)

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Emma Guttman-Yassky, Kenji Kabashima, Delphine Staumont, Walter K. Nahm, Sylvia Pauser, et al.. Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years.. Allergy, 2024, Allergy, 79, pp.1560-1572. ⟨10.1111/all.16108⟩. ⟨hal-04679825⟩

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