Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis.
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 IgG(1) 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.


CONCLUSIONS
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.


CONCLUSIONS
Anti-IL-5 is a promising therapeutic intervention for EE.
Stein
Miguel L
ML
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Collins
Margaret H
MH
Villanueva
Joyce M
JM
Kushner
Jonathan P
JP
Putnam
Philip E
PE
Buckmeier
Bridget K
BK
Filipovich
Alexandra H
AH
Assa'ad
Amal H
AH
Rothenberg
Marc E
ME
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001706:Biopsy; D004334:Drug Administration Schedule; D004802:Eosinophilia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology; D004941:Esophagitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D008297:Male; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C515350:CCR3 protein, human; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; C434107:mepolizumab