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

Miguel L. Stein, Margaret H. Collins, Joyce M. Villanueva, Jonathan P. Kushner, Philip E. Putnam, Bridget K. Buckmeier, Alexandra H. Filipovich, Amal H. Assa'ad, Marc E. Rothenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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 positively regulates eosinophil growth, activation, survival, and tissue recruitment. Objective: We hypothesized that the humanized monoclonal IgG1 antibody against human IL-5 (mepolizumab) may be useful in the control of EE. Methods: 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 of esophageal biopsies were determined before and 1 month after treatment. Results: 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. Conclusion: 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. Clinical implications: Anti-IL-5 is a promising therapeutic intervention for EE.

Original languageEnglish
Pages (from-to)1312-1319
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume118
Issue number6
DOIs
StatePublished - Dec 2006
Externally publishedYes

Keywords

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

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