Anti–IL-5 (mepolizumab) therapy for eosinophilic esophagitis - 20/08/11
Reprint 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.Cincinnati, Ohio
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.
El texto completo de este artículo está disponible en PDF.Key words : Anti–IL-5, cytokine, eosinophils, eosinophilia, esophagitis, eotaxin-3, mepolizumab, IL-5
Abbreviations used : EE, EGID, GERD, hpf
Esquema
| 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. |
Vol 118 - N° 6
P. 1312-1319 - décembre 2006 Regresar al número
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