Dupilumab in hypereosinophilic syndrome: promise and caution
Published online November 6, 2024
Dupilumab is an Il-4Ra monoclonal antibody receptor antagonist and is FDA approved for eosinophilic asthma, chronic rhinosinusitis with nasal polyps, and atopic dermatitis. Dupilumab has been associated with a moderate and temporary increase in blood eosinophil counts, though there have been reports of hypereosinophilia (absolute eosinophil count ≥ 1.5 x 109/L) and eosinophil-related complications, such as eosinophilic pneumonia and eosinophilic granulomatosis and polyangiitis (EGPA). Thus, the safety and efficacy of dupilumab use in patients with preexisting hypereosinophilia remain uncertain.
A recent article published in The Journal of Allergy and Clinical Immunology: In Practice by Ezekwe et al. looked at whether eosinophil-related complications of dupilumab are increased in patients diagnosed with hypereosinophilic syndrome (HES). The authors conducted a retrospective chart review of patients with HES who received dupilumab therapy and were followed at the National Institutes of Health (NIH) or Walter Reed National Military Medical Center (WRNMMC) through September 30, 2023. Clinical response and treatment-emergent adverse events were recorded. A treatment-emergent adverse event (TEAE) was defined as any complication that developed while a patient was on dupilumab therapy that led to stopping dupilumab and/or adding a new HES therapy. The study also measured serum factors associated with eosinophilia in a subset of patients. In addition to the chart review, published cases of patients with hypereosinophilia who received dupilumab therapy were summarized.
Among the 28 patients with HES treated with dupilumab and followed at the NIH or WRNMMC, 23 (82%) reported symptomatic improvement. The median age of the patients was 41.5 years, and the most common diagnosis was HES overlap (71%). The median duration of dupilumab treatment was 24 months, and the geometric mean peak absolute eosinophil count (AEC) before treatment was 3.18 x 109/L. Although dupilumab was effective in improving symptoms in many patients, AEC increased in 20 of 26 patients, with nine patients developing hypereosinophilia and four developing eosinophil-related complications, including eosinophilic pleural effusion and coronary artery dissection. In contrast, patients treated with dupilumab in combination with an eosinophil-lowering biologic had minimal increases in AEC and no reported adverse events. Serum IgE and eotaxin levels decreased significantly following dupilumab initiation, while biologically active IL-5 levels were generally undetectable. Data abstracted from the published cases supported the findings from the retrospective study. Overall, the study suggests that dupilumab may be effective in treating HES, but its use is associated with an increased risk of eosinophil-related adverse events, particularly in patients with high baseline AEC.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.
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