Amlitelimab Reduces Th2-, Th1-, and Th17/22-Related Cytokines and Chemokines in Adults With Moderate-to-Severe Atopic Dermatitis: Results From an Exploratory Analysis of the Phase 2b STREAM-AD Study
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Keywords
Atopic dermatitis, Amlitelimab
Abstract
Introduction Amlitelimab, a fully human, nondepleting monoclonal antibody, binds OX40 ligand (OX40L) on antigen-presenting cells, preventing OX40L-OX40 interaction on activated T cells. In adults with moderate-to-severe atopic dermatitis (AD), amlitelimab demonstrated clinically meaningful improvements in AD lesions and pruritus, and reduced AD-related plasma and cutaneous biomarkers over 24 weeks compared with placebo-treated patients in Part 1 of STREAM-AD. This analysis evaluates the effect of amlitelimab on AD-related cytokines and chemokines, including those associated with Th2, Th1, and Th17/Th22 inflammation.
Methods STREAM-AD (NCT05131477) was a 52-week, Phase 2b trial with two parts: a 24-week dose-ranging phase and a 28-week maintenance phase. In Part 1, adults with moderate-to-severe AD were randomized to receive subcutaneous amlitelimab (250mg with 500-mg loading dose, 250mg, 125mg, 62.5mg) or placebo every 4 weeks. Here, changes in inflammatory proteins from baseline to weeks 4 and 16 were evaluated utilizing an exploratory protein multiplex panel (Olink® Explore 384 Inflammation I, Olink Proteomics) on plasma from patients with AD treated with amlitelimab (n=300) vs placebo (n=76) in Part 1.
Results Amlitelimab reduced plasma proteins associated with Th2 inflammation, including CCL13, CCL17, CCL22, CCL26, IL-13, and IL-24 (P<0.01 for all) from baseline to Week 16. It also reduced markers of Th1-related inflammation, including CXCL9, CXCL10, and TNF (P<0.01 for all), and Th17/22-related inflammation, including CCL20, IL-17A, IL-17C (P<0.01 for all), and IL-6 (P<0.05).
Conclusion Amlitelimab significantly reduced proteins associated with AD inflammation in adults with moderate-to-severe AD, further supporting that OX40L blockade is a relevant target for treating AD-related inflammation.
References
2. Fu N, Xie F, Sun Z, Wang Q. The OX40/OX40L Axis Regulates T Follicular Helper Cell Differentiation: Implications for Autoimmune Diseases. Front Immunol. 2021;12:670637. Published 2021. doi:10.3389/fimmu.2021.670637
3. Weidinger S, Blauvelt A, Papp KA, et al. Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2025;155(4):1264-1275. doi:10.1016/j.jaci.2024.10.031
4. Geng B, et al. Oral presentation at EAACI; June 1, 2024; Valencia, Spain
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