Scalp biomarkers during dupilumab treatment support Th2 pathway pathogenicity in alopecia areata

作者：Yael Renert‐Yuval, Ana B. Pavel, Ester Del Duca, Paola Facheris, Angel D. Pagan, Swaroop Bose, P. Gomez-Arias, Michael Angelov, Jennifer Bares, Margo Chima, Yeriel Estrada, Sandra Garcet, Mark Lebwohl, James G. Krueger, Emma Guttman‐Yassky · 发表于：Allergy · 年份：2022 · DOI：10.1111/all.15561 · 被引用次数：55 · 研究领域：Hair Growth and Disorders、Dermatology and Skin Diseases、Psoriasis: Treatment and Pathogenesis

BACKGROUND: The mechanisms driving alopecia areata (AA) are still unclear, hindering development of targeted therapeutics. Specific Th2 targeting with dupilumab in AA provides a unique opportunity to dissect its pathogenesis and explore the role of Th2 pathway. METHODS: We evaluated changes in scalp biomarkers in AA patients (with and without concomitant atopy) randomized to weekly dupilumab or placebo for 24 weeks, followed by open-label dupilumab for 24 weeks. Changes in biomarker levels were measured at weeks 12, 24, and 48 and were also correlated with clinical hair regrowth. RESULTS: At week 24, preceding clinical hair regrowth outcomes, only dupilumab-treated patients presented significant suppression of cellular infiltrates, and multiple Th2-related, markers (CCL13/MCP-4, CCL18/PARC, CCL26/eotaxin-3, CCL24/Eotaxin-2), coupled with significant upregulation in the hair keratins. Th1-related suppression was evident later (week 48) when all patients received open-label dupilumab. Results were more pronounced in atopic AA patients, that showed 48% and 97% improvements in the lesional AA scalp profile at weeks 24 and 48, respectively, while 2% worsening was seen in the placebo arm at week 24. Moreover, placebo-treated patients presented 54% worsening in hair keratins when compared with baseline at week 24. At week 24, increases in hair keratins showed significant correlations only with decreases in Th2-related markers. CONCLUSIONS: Scalp biomarkers provide evidence of dupilu...