Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis.
Stein, Miguel L. MD a; Collins, Margaret H. MD b; Villanueva, Joyce M. BS c; Kushner, Jonathan P. MD e; Putnam, Philip E. MD d; Buckmeier, Bridget K. BA a; Filipovich, Alexandra H. MD c; Assa'ad, Amal H. MD a; Rothenberg, Marc E. MD, PhD a
[Miscellaneous Article]
Journal of Allergy & Clinical Immunology.
118(6):1312-1319, December 2006.
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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 (x400; 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.
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