Fei Li Kuang1, Michelly Sampaio De Melo2, Michelle Makiya3, Sheila Kumar4, Thomas Brown3, Lauren Wetzler3, JeanAnne M Ware3, Paneez Khoury3, Margaret H Collins5, Martha Quezado2, Stefania Pittaluga2, Amy D Klion3. 1. Division of Allergy Immunology, Northwestern University Feinberg School of Medicine, Chicago, Ill; Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: feili.kuang@northwestern.edu. 2. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md. 3. Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. 4. Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md. 5. Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Abstract
BACKGROUND: Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion with anticytokine (anti-IL-5) treatments and/or irreversible fibrotic tissue changes contributing to symptomatology. OBJECTIVE: To characterize the therapeutic effect of eosinophil depletion in patients with hypereosinophilic syndrome with varied eosinophilic gastrointestinal (GI) disorders. METHODS: Hematologic, histologic, endoscopic, and clinical symptoms for a subset (n = 7) of hypereosinophilic syndrome patients with GI tissue eosinophilia enrolled in a phase 2 clinical trial of benralizumab (anti-IL-5RA) were assessed before and after treatment (NCT02130882). RESULTS: Blood and GI tissue eosinophils were completely depleted in all segments of the GI tract, and all patients reported improved GI symptoms, in some cases as early as after the first monthly dose. Some patients had recurrent symptomatic flares without recurrent peripheral or tissue eosinophilia, in most cases after prolonged symptomatic remission and in the setting of liberalization of dietary restrictions and/or tapering of background therapy. Although eosinophil-associated histologic changes improved in all segments, epithelial changes persisted in the esophagus and stomach in patients with recurrent disease flares even after 1 year of treatment. Serum tryptase and GI mast cells were generally unchanged with treatment, and increases were not associated with disease flares. Serum levels of IL-4 and IL-5 increased with benralizumab treatment (both P < .05). CONCLUSIONS: Benralizumab treatment completely depleted blood and GI tissue eosinophilia in patients with eosinophilic GI disorders, but clinical response, while encouraging, was heterogeneous. Residual symptoms in some patients may reflect persistent epithelial changes in the upper GI tract.
BACKGROUND: Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion with anticytokine (anti-IL-5) treatments and/or irreversible fibrotic tissue changes contributing to symptomatology. OBJECTIVE: To characterize the therapeutic effect of eosinophil depletion in patients with hypereosinophilic syndrome with varied eosinophilic gastrointestinal (GI) disorders. METHODS: Hematologic, histologic, endoscopic, and clinical symptoms for a subset (n = 7) of hypereosinophilic syndrome patients with GI tissue eosinophilia enrolled in a phase 2 clinical trial of benralizumab (anti-IL-5RA) were assessed before and after treatment (NCT02130882). RESULTS: Blood and GI tissue eosinophils were completely depleted in all segments of the GI tract, and all patients reported improved GI symptoms, in some cases as early as after the first monthly dose. Some patients had recurrent symptomatic flares without recurrent peripheral or tissue eosinophilia, in most cases after prolonged symptomatic remission and in the setting of liberalization of dietary restrictions and/or tapering of background therapy. Although eosinophil-associated histologic changes improved in all segments, epithelial changes persisted in the esophagus and stomach in patients with recurrent disease flares even after 1 year of treatment. Serum tryptase and GI mast cells were generally unchanged with treatment, and increases were not associated with disease flares. Serum levels of IL-4 and IL-5 increased with benralizumab treatment (both P < .05). CONCLUSIONS: Benralizumab treatment completely depleted blood and GI tissue eosinophilia in patients with eosinophilic GI disorders, but clinical response, while encouraging, was heterogeneous. Residual symptoms in some patients may reflect persistent epithelial changes in the upper GI tract.
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