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

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.