TY - JOUR
T1 - Benralizumab Completely Depletes Gastrointestinal Tissue Eosinophils and Improves Symptoms in Eosinophilic Gastrointestinal Disease
AU - Kuang, Fei Li
AU - De Melo, Michelly Sampaio
AU - Makiya, Michelle
AU - Kumar, Sheila
AU - Brown, Thomas
AU - Wetzler, Lauren
AU - Ware, Jean Anne M.
AU - Khoury, Paneez
AU - Collins, Margaret H.
AU - Quezado, Martha
AU - Pittaluga, Stefania
AU - Klion, Amy D.
N1 - Publisher Copyright:
© 2022 American Academy of Allergy, Asthma & Immunology
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Eosinophilia
KW - Eosinophilic colitis
KW - Eosinophilic enteritis
KW - Eosinophilic esophagitis
KW - Eosinophilic gastritis
KW - Hypereosinophilic syndrome
KW - mAb
UR - http://www.scopus.com/inward/record.url?scp=85127327673&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127327673&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2022.02.037
DO - 10.1016/j.jaip.2022.02.037
M3 - Article
C2 - 35283330
AN - SCOPUS:85127327673
SN - 2213-2198
VL - 10
SP - 1598-1605.e2
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 6
ER -