Anti–IL-5 (mepolizumab) therapy for eosinophilic esophagitis

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作者：

M Stein，M Collins，J Villanueva，J Kushner，P Putnam，B Buckmeier，A Filipovich，A Assaad，M Rothenberg

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摘要：

Eosinophilic esophagitis (EE) is characterized by high numbers of eosinophils in the esophagus and epithelial hyperplasia, and is being increasingly recognized. IL-5 promotes eosinophil trafficking to the esophagus, and positivelyregulates eosinophil growth, activation, survival, and tissue recruitment. We hypothesized that the humanized monoclonal IgG 1 antibody against human IL-5 (mepolizumab) may be useful in the control of EE. An open-label phase I/II safety and efficacy study of anti–IL-5 in 4 adult patients with EE and longstanding dysphagia and esophageal strictures was conducted. Patients received 3 infusions of anti–IL-5 (750 mg intravenously monthly) without change in their current therapy. The levels of plasma IL-5, peripheral blood eosinophils, and CCR3 + cells in blood, quality of life measurements, and histological analysis ofesophageal biopsies were determined before and 1 month after treatment. Peripheral blood eosinophilia and percent of CCR3 + cells decreased by 6.4-fold and 7.9-fold ( P < .05), respectively, after anti–IL-5 treatment. Notably, mean and maximal esophageal eosinophilia decreased from 46 to 6 and from 153 to 28 eosinophils/high-power field (×400; average, 8.9-fold, P < .001, and 6-fold, P < .05), respectively. Patients reported a better clinical outcome and improved quality of life ( P = .03). Therapy was generally well tolerated, and responsiveness to anti–IL-5 therapy did not correlate with plasma IL-5 levels. Anti–IL-5 therapy is associated with marked decreases in peripheral blood and esophageal eosinophilia (including the number of CCR3 + blood cells) in patients with EE and improved clinical outcomes. Anti–IL-5 is a promising therapeutic intervention for EE.

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关键词：

Anti–IL-5 cytokine eosinophils eosinophilia esophagitis eotaxin-3 mepolizumab IL-5