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

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 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.

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.

• Authors: 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
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 118 Issue 6 Pg. 1312-9 (Dec 2006) ISSN: 0091-6749 [Print] United States
• PMID: 17157662 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CCR3 protein, human
• Receptors, CCR3
• Receptors, Chemokine
• mepolizumab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Biopsy
• Drug Administration Schedule
• Eosinophilia (drug therapy, immunology, pathology)
• Eosinophils (immunology)
• Esophagitis (drug therapy, immunology, pathology)
• Esophagus (pathology)
• Female
• Humans
• Infusions, Intravenous
• Leukocyte Count
• Male
• Receptors, CCR3
• Receptors, Chemokine
• T-Lymphocytes (immunology)
• Treatment Outcome