Dupilumab Use in Patients With Hypereosinophilic Syndromes: A Multicenter Case Series and Review of the Literature

Ejiofor A D Ezekwe Jr; Andrew L Weskamp; Rodaba Rahim; Michelle A Makiya; Lauren Wetzler; JeanAnne M Ware; Celeste Nelson; Perla Adames Castillo; Charles A Riley; Thomas Brown; Lori Penrod; Gregory M Constantine; Paneez Khoury; Nathan A Boggs; Amy D Klion

doi:10.1016/j.jaip.2024.10.036

Dupilumab Use in Patients With Hypereosinophilic Syndromes: A Multicenter Case Series and Review of the Literature

J Allergy Clin Immunol Pract. 2024 Nov 6:S2213-2198(24)01119-X. doi: 10.1016/j.jaip.2024.10.036. Online ahead of print.

Authors

Affiliations

¹ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
² Allergy, Immunology, & Immunizations Service, Walter Reed National Military Medical Center, Bethesda, Md.
³ Otolaryngology, Head and Neck Surgery, Walter Reed National Military Medical Center, Bethesda, Md; Department of Surgery, Uniformed Services University, Bethesda, Md.
⁴ Allergy, Immunology, & Immunizations Service, Walter Reed National Military Medical Center, Bethesda, Md; Department of Medicine, Uniformed Services University, Bethesda, Md.
⁵ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: amy.klion@nih.gov.

PMID: 39515522
DOI: 10.1016/j.jaip.2024.10.036

Abstract

Background: Hypereosinophilic syndromes (HES) are defined as hypereosinophilia with eosinophil-related clinical manifestations, some of which overlap in presentation with asthma, atopic dermatitis, eosinophilic esophagitis, and/or chronic rhinosinusitis with nasal polyps. Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count and rare eosinophil-related complications.

Objective: To determine whether eosinophil-related complications of dupilumab are increased in HES.

Methods: Retrospective chart review of patients with HES treated with dupilumab enrolled on an institutional review board-approved research protocol at the National Institutes of Health (NCT00001406) or receiving care at Walter Reed National Military Medical Center. Clinical response and treatment-emergent adverse events were recorded. Serum mediators were assessed in a subset of patients before and after dupilumab using stored samples.

Results: Among the 28 patients (15 male, 13 female; median age 41.5 y), the most common prescribing indication for dupilumab was chronic rhinosinusitis with nasal polyps (n = 11). Twenty-three patients (82%) showed significant clinical improvement on dupilumab. Hypereosinophilia (absolute eosinophil count > 1.5 × 10⁹/L) recurred or worsened in 9 of 20 patients on dupilumab monotherapy. Moreover, 4 of 20 (20%) patients developed an eosinophil-related complication with dupilumab discontinuation and/or addition of eosinophil-lowering therapy. None of the 8 patients who received dupilumab while in hematological remission on an eosinophil-lowering biologic developed hypereosinophilia or an eosinophil-related complication. Serum immunoglobulin E and eotaxin levels decreased on dupilumab therapy.

Conclusions: These data suggest that dupilumab is effective in treating residual symptoms in HES patients but that the incidence of eosinophil-related complications is increased. Concomitant eosinophil-lowering therapy may reduce the risk of eosinophil-related complications during dupilumab therapy in patients with HES.

Keywords: Benralizumab; Biologic therapy; Dupilumab; Eosinophil; Hypereosinophilia; Hypereosinophilic syndrome; Mepolizumab; Reslizumab.

Published by Elsevier Inc.