Dupilumab as Add-On Therapy for Hypereosinophilic Syndrome With Partial Clinical Response to Eosinophil-Depleting Biologic Agents

Inclusion criteria

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Age \>=18 years
• Documented diagnosis of HES with historic AEC\>1.5x10\^9/L on two occasions, no secondary etiology for the eosinophilia despite careful clinical evaluation, and evidence of end organ damage (histologic evidence of tissue infiltration by eosinophils and/or objective evidence of clinical pathology in any organ system that is temporally associated with eosinophilia and not clearly attributable to another cause)
• Currently receiving treatment with an eosinophil-lowering biologic (mepolizumab, reslizumab, or benralizumab) for a minimum of 24 weeks
• AEC\<0.5x10\^9/L
• Residual symptoms after a minimum of 24 weeks of eosinophil-lowering biologic therapy with at least 1 most bothersome symptom of moderate severity (HES-SI score \>=2) consistent with \>=1 of the following diagnoses: a. asthma, defined as physician-documented asthma requiring medium to high dose inhaled corticosteroids + long-acting beta agonist b. atopic dermatitis, defined as physician-documented chronic or recurrent inflammatory skin disease c. CRSwNP, defined as evidence of rhinosinusitis and nasal polyposis on physical examination or imaging d. EoE, defined as biopsy-proven esophageal eosinophilia \>15 eosinophils/high power field
• For participants who can become pregnant: sexual abstinence or use of highly effective contraception (i.e., partner vasectomy, bilateral tubal ligation, IUD, progestin implants, and other hormonal methods) starting 4 weeks prior to study drug initiation and agreement to use such a method during study participation and for an additional 12 weeks after the end of study drug administration
• Participation in NIH protocol 94-I-0079 (Activation and function of eosinophils in conditions with blood or tissue eosinophilia)
• Ability of subject to understand and the willingness to sign a written informed consent document

Exclusion criteria

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy or lactation
• Known allergic reaction to dupilumab or any of the excipients in Dupixent(TM)
• Febrile illness within 7 days of enrollment
• Treatment with an investigational drug or other intervention other than mepolizumab, reslizumab, or benralizumab within 12 weeks or 4 half-lives of the investigational agent (whichever is longer).
• Known or suspected acquired or inborn immunodeficiency disorder, including HIV infection
• Known diagnosis of eosinophilic granulomatosis with polyangiitis
• Change in eosinophil-active therapy within the past 6 weeks, including but not limited to topical corticosteroids, leukotriene inhibitors, initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food (in patients with gastrointestinal involvement), and proton pump inhibitors (in patients with gastrointestinal involvement)
• Planned or anticipated major surgical procedure during the study
• Active parasitic infection
• History of malignancy within 5 years, excluding completely treated in situ carcinoma of the cervix, or squamous or basal cell carcinoma of the skin
• Any condition that, in the investigator s opinion, places the patient at undue risk by participating in the study For patients with eosinophilic gastrointestinal disease only:
• Active infection with Helicobacter pylori
• History of achalasia, Crohn s disease, ulcerative colitis, celiac disease, or prior esophageal surgery
• Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to 10 mm upper endoscope