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 (CRSwNP). Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count (AEC) 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 IRB-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), the most common prescribing indication for dupilumab was CRSwNP (n=11). Twenty-three patients (82%) showed significant clinical improvement on dupilumab. Hypereosinophilia (AEC >1.5x10⁹/L) recurred or worsened in 9/20 patients on dupilumab monotherapy. Moreover, 4/20 (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 hematologic remission on an eosinophil-lowering biologic developed hypereosinophilia or an eosinophil-related complication. Serum IgE and eotaxin levels decreased on dupilumab therapy.

Conclusion: 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.