Transient eosinophilia with dupilumab rarely of clinical significance and does not affect efficacy

Published: May 27, 2022

Eosinophils are inflammatory cells that are associated with exacerbations in inflammatory diseases such as asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps (CRSwNP), and eosinophilic esophagitis. Transient increases in blood eosinophil counts (eosinophilia) have been observed in clinical trials with dupilumab, generally during the first few weeks of treatment, with levels returning to normal. This rise in blood eosinophilia is to be expected, and a potential mechanism may be the blocking of interleukin-4 and interleukin-13-mediated trafficking of eosinophils from the blood into tissue.

To determine whether such transient eosinophilia has any effect on the efficacy of dupilumab or has any clinical relevance, Wechsler et al. analyzed data from 11 clinical trials of dupilumab and examined eosinophil counts; rates of eosinophilia-related adverse events, treatment-emergent eosinophilia (>1500 cells/µL), and treatment discontinuation; clinical symptoms; and treatment efficacy in patients who had eosinophilia upon treatment with dupilumab. Their findings are published in The Journal of Allergy and Clinical Immunology: In Practice.

The analysis showed that mean eosinophil counts increased upon treatment with dupilumab in three of four patient groups. In patients with asthma, counts increased from a baseline of 349–370 cells/µL (mean range across studies) to 515–578 cells/µL by the fourth week of treatment; in patients with CRSwNP, counts increased from 440–448 cells/µL to 595 cells/µL by week 16; and in patients with atopic dermatitis, counts increased from 434–600 cells/µL to 410–710 cells/µL by week 4. In all three groups, these increases were followed by a decline in counts to baseline level or lower that started at week 24 of treatment. Patients with eosinophilic esophagitis overall had no increase in eosinophil count, which was 310 cells/µL at baseline and 230 cells/µL at week 4. Adverse events due to eosinophilia that emerged upon treatment with dupilumab occurred in 0 to 13.6% of patients overall in the 11 trials. Clinical symptoms associated with eosinophilia were rare and observed in only 7 of 4,666 patients treated with dupilumab. Those symptoms, including eosinophilic granulomatosis with polyangiitis (6 cases) and eosinophilic pneumonia (1 case), were seen only in patients with asthma or CRSwNP. There was no reduction in the efficacy of dupilumab as a result of eosinophilia.

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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