1. Lebrikizumab reduces systemic inflammation in serum of patients with moderate-to-severe atopic dermatitis.
- Author
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Guttman-Yassky, Emma, Okragly, Angela, Zhe Sun, Mena, Laura Rebeca, Hahn, Nathan, Nickoloff, Brian J., Siu, Kimberly, Gallo, Gaia, Wolf, Eric, Eyerich, Kilian, Aparici, Monica, and Benschop, Robert J.
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ATOPIC dermatitis , *PERIOSTIN , *INFLAMMATION , *IMMUNOGLOBULIN E , *CHEMOKINES - Abstract
Introduction Lebrikizumab is an interleukin (IL)-13 inhibitor that has completed phase 3 studies. It demonstrated statistical superiority vs. placebo in patients with moderate-to-severe atopic dermatitis (AD) across all primary and key secondary endpoints at week 4 and week 16 of ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Objectives: The objective of this analysis is to determine lebrikizumab's impact on AD-relevant serum biomarkers in patients from these studies through week 16. Methods: Protein biomarkers were determined in available serum samples from patients receiving lebrikizumab 250 mg every 2 weeks (n=72) or placebo (n=36) from both ADvocate1 and ADvocate2. Pre- and post-treatment biomarkers were compared to healthy controls (HC, n=30) which were age, sex, race, and ethnically matched. The analysis included biomarkers known to be elevated in AD. IL-13 was only measured at baseline because of lebrikizumab's known interference with IL-13 measurement. Results: At baseline, CCL13, CCL17, CCL22, total IgE, IL-5, IL-13, and periostin were elevated in patients with AD (p<0.001) with IL-13 measuring approximately 7-fold greater in the AD population vs. HC. In patients with AD, IL-4, CCL11, CXCL10, CCL2, and CCL4 were not elevated at baseline vs. HC.At week 4, lebrikizumab significantly reduced levels of the key type 2 biomarkers, CCL13, CCL17, and periostin vs. placebo (p<0.01) with a trend toward levels consistent with HC (within 1.5-fold). At week 16, CCL13, CCL17, and periostin levels remained consistent with HC levels with CCL13 and periostin retaining statistically significant reductions vs. placebo (p<0.01). Conclusions: In sum, selective targeting of IL-13 with lebrikizumab monotherapy reduced known molecular biomarkers of systemic type 2 inflammation in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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