Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis
Abstract Introduction Lebrikizumab is a novel monoclonal antibody that selectively binds to interleukin (IL)-13 with high affinity and a slow dissociation rate. Methods We assayed serum from select patients enrolled in ADvocate1 and ADvocate2 to determine the impact of lebrikizumab on circulating bi...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2025-07-01
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| Series: | Dermatology and Therapy |
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| Online Access: | https://doi.org/10.1007/s13555-025-01481-4 |
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| author | Emma Guttman-Yassky Zhe Sun Laura Rebeca Mena Nathan Hahn Brian J. Nickoloff Christoph Preuss Kimberly Siu Chitra R. Natalie Gaia Gallo Eric Wolf Kilian Eyerich Mònica Aparici Robert J. Benschop Angela Okragly |
| author_facet | Emma Guttman-Yassky Zhe Sun Laura Rebeca Mena Nathan Hahn Brian J. Nickoloff Christoph Preuss Kimberly Siu Chitra R. Natalie Gaia Gallo Eric Wolf Kilian Eyerich Mònica Aparici Robert J. Benschop Angela Okragly |
| author_sort | Emma Guttman-Yassky |
| collection | DOAJ |
| description | Abstract Introduction Lebrikizumab is a novel monoclonal antibody that selectively binds to interleukin (IL)-13 with high affinity and a slow dissociation rate. Methods We assayed serum from select patients enrolled in ADvocate1 and ADvocate2 to determine the impact of lebrikizumab on circulating biomarkers and pathways relevant to atopic dermatitis (AD) and to assess the correlation between key biomarkers and clinical measures of improvement. Results At baseline, IL-13, CC motif chemokine ligand (CCL)13, CCL17, CCL22, total immunoglobulin (Ig)E, IL-5, and periostin were elevated in patients with moderate-to-severe AD versus healthy controls (p < 0.001). Baseline Eczema and Area Severity Index (EASI) and Investigator’s Global Assessment (IGA) scores were significantly correlated with IL-13, IL-5, CCL13, CCL22, and CCL26. Lebrikizumab induced rapid and progressive reductions in CCL13, CCL17, CCL22, and periostin at weeks 4, 16, and 52 compared with baseline (p < 0.05). AD-associated pathways linked to cytokine signaling were significantly improved at weeks 4 and 16. Improvements in EASI, IGA, and the Pruritus Numeric Rating Scale were correlated with reductions in CCL13, CCL17, CCL22, CCL26, and periostin across all time points. After multiple testing correction and adjusting for sex and race as covariates, we identified the chemokine CCL26 as a pharmacodynamic marker for lebrikizumab response at weeks 4 and 16. Conclusions Selective inhibition of IL-13 with lebrikizumab monotherapy induced progressive inhibition of systemic biomarkers and pathways of type 2 inflammation, which correlated with clinical measures of improvement in patients with moderate-to-severe AD. Clinical Trial Registrations NCT04146363 and NCT04178967. |
| format | Article |
| id | doaj-art-973fd72010414622aecadb1e50c9388a |
| institution | Kabale University |
| issn | 2193-8210 2190-9172 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Adis, Springer Healthcare |
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| series | Dermatology and Therapy |
| spelling | doaj-art-973fd72010414622aecadb1e50c9388a2025-08-20T03:42:34ZengAdis, Springer HealthcareDermatology and Therapy2193-82102190-91722025-07-011592595261410.1007/s13555-025-01481-4Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic DermatitisEmma Guttman-Yassky0Zhe Sun1Laura Rebeca Mena2Nathan Hahn3Brian J. Nickoloff4Christoph Preuss5Kimberly Siu6Chitra R. Natalie7Gaia Gallo8Eric Wolf9Kilian Eyerich10Mònica Aparici11Robert J. Benschop12Angela Okragly13Department of Dermatology, Icahn School of Medicine at Mount SinaiEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyNet2Source IncEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyEli Lilly and CompanyDepartment of Dermatology, Medical Center, University of FreiburgAlmirall, S.AEli Lilly and CompanyEli Lilly and CompanyAbstract Introduction Lebrikizumab is a novel monoclonal antibody that selectively binds to interleukin (IL)-13 with high affinity and a slow dissociation rate. Methods We assayed serum from select patients enrolled in ADvocate1 and ADvocate2 to determine the impact of lebrikizumab on circulating biomarkers and pathways relevant to atopic dermatitis (AD) and to assess the correlation between key biomarkers and clinical measures of improvement. Results At baseline, IL-13, CC motif chemokine ligand (CCL)13, CCL17, CCL22, total immunoglobulin (Ig)E, IL-5, and periostin were elevated in patients with moderate-to-severe AD versus healthy controls (p < 0.001). Baseline Eczema and Area Severity Index (EASI) and Investigator’s Global Assessment (IGA) scores were significantly correlated with IL-13, IL-5, CCL13, CCL22, and CCL26. Lebrikizumab induced rapid and progressive reductions in CCL13, CCL17, CCL22, and periostin at weeks 4, 16, and 52 compared with baseline (p < 0.05). AD-associated pathways linked to cytokine signaling were significantly improved at weeks 4 and 16. Improvements in EASI, IGA, and the Pruritus Numeric Rating Scale were correlated with reductions in CCL13, CCL17, CCL22, CCL26, and periostin across all time points. After multiple testing correction and adjusting for sex and race as covariates, we identified the chemokine CCL26 as a pharmacodynamic marker for lebrikizumab response at weeks 4 and 16. Conclusions Selective inhibition of IL-13 with lebrikizumab monotherapy induced progressive inhibition of systemic biomarkers and pathways of type 2 inflammation, which correlated with clinical measures of improvement in patients with moderate-to-severe AD. Clinical Trial Registrations NCT04146363 and NCT04178967.https://doi.org/10.1007/s13555-025-01481-4Atopic dermatitisBiomarkersInterleukin-13Lebrikizumab |
| spellingShingle | Emma Guttman-Yassky Zhe Sun Laura Rebeca Mena Nathan Hahn Brian J. Nickoloff Christoph Preuss Kimberly Siu Chitra R. Natalie Gaia Gallo Eric Wolf Kilian Eyerich Mònica Aparici Robert J. Benschop Angela Okragly Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis Dermatology and Therapy Atopic dermatitis Biomarkers Interleukin-13 Lebrikizumab |
| title | Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis |
| title_full | Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis |
| title_fullStr | Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis |
| title_full_unstemmed | Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis |
| title_short | Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis |
| title_sort | lebrikizumab rapidly lowers inflammatory biomarkers with clinical correlations in moderate to severe atopic dermatitis |
| topic | Atopic dermatitis Biomarkers Interleukin-13 Lebrikizumab |
| url | https://doi.org/10.1007/s13555-025-01481-4 |
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