The Journal of Allergy and Clinical Immunology
Volume 118, Issue 6 , Pages 1312-1319, December 2006

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

  • Miguel L. Stein, MD

      Affiliations

    • From the Divisions of Allergy and Immunology
    • ,
  • Margaret H. Collins, MD

      Affiliations

    • Pathology and Laboratory Medicine
    • ,
  • Joyce M. Villanueva, BS

      Affiliations

    • Hematology/Oncology
    • ,
  • Jonathan P. Kushner, MD

      Affiliations

    • Digestive Diseases, University of Cincinnati College of Medicine
    • ,
  • Philip E. Putnam, MD

      Affiliations

    • Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center
    • ,
  • Bridget K. Buckmeier, BA

      Affiliations

    • From the Divisions of Allergy and Immunology
    • ,
  • Alexandra H. Filipovich, MD

      Affiliations

    • Hematology/Oncology
    • ,
  • Amal H. Assa'ad, MD

      Affiliations

    • From the Divisions of Allergy and Immunology
    • ,
  • Marc E. Rothenberg, MD, PhD

      Affiliations

    • From the Divisions of Allergy and Immunology
    • Corresponding Author InformationReprint requests: Marc E. Rothenberg, MD, PhD, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH 45229.

Received 11 August 2006; received in revised form 1 September 2006; accepted 7 September 2006. published online 10 November 2006.

Cincinnati, Ohio

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.

Key words: Anti–IL-5, cytokine, eosinophils, eosinophilia, esophagitis, eotaxin-3, mepolizumab, IL-5

Abbreviations used: EE, Eosinophilic esophagitis, EGID, Eosinophilic gastrointestinal disorder, GERD, Gastroesophageal reflux disease, hpf, High-power field

 

 Supported by grants from the Food and Drug Administration #FD-R 002313 and the Burroughs Wellcome Fund (M. E. Rothenberg), the Campaign Urging Research for Eosinophilic Diseases Foundation, and the Buckeye Foundation. M. L. Stein is a recipient of a fellowship from the American Physicians Fellowship for Medicine in Israel.Disclosure of potential conflict of interest: M. E. Rothenberg has consultant arrangements with GlaxoSmithKline, Ception Therapeutics, Cambridge Antibody Technology, and MedaCorp; owns stock in Ception Therapeutics; has received grant support from Cambridge Antibody Technology; is on the speakers' bureau for Merck; and has received honoraria from GlaxoSmithKline, Ception Therapeutics, Merck, and Tanox. M. H. Collins and A. H. Assa'ad have consulting arrangements with and have received grant support from GlaxoSmithKline. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(06)01904-X

doi:10.1016/j.jaci.2006.09.007

The Journal of Allergy and Clinical Immunology
Volume 118, Issue 6 , Pages 1312-1319, December 2006

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