D1.96 - Impact of Dupilumab-induced Eosinophilia on Pulmonary Function Tests and Patient Reported Outcomes Measures (PROMs)

Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of interleukin (IL)-4 receptor, is currently approved for the treatment of T2-high severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe atopic dermatitis. Blood eosinophil count >500 cells/µL is a well-known adverse effect. Hypereosinophilia >1500 cells/µL is estimated in about 2% of patients. We aim to evaluate whether pulmonary function tests and patient-reported outcome measures (PROMs) for asthma and CRSwNP patients may be affected by this increase.

Retrospective study including patients with asthma and CRSwNP treated with dupilumab, who presented with induced eosinophilia (2022-2024). Blood eosinophil count, pulmonary function tests (FEV1, FVC, FEV1/FVC, TLC, RV and exhaled nitric oxide) and PROMs (ACT, CARAT, SNOT-22 and mini-AQLQ) were performed before starting treatment and at 4, 8 and 12 months. Demographic and clinical data were collected from clinical files. Informed consent was obtained from all patients. Statistical analysis IBM SPSS 25®.

We included 7 patients, 4 (26.7%) of whom with dupilumab-related eosinophilia and 3 (20%) with hypereosinophilia. The majority were female (n=4, 57.1%), mean age of 54.4+3.0 [32-82] years. Mean duration of treatment was 17.7+1 [12-22] months – table I. Mean blood eosinophil count at T0 was 780+100 [420-1270] cells/µL, with an increase in T4 and a decrease in T12, both not statistically significant – table II. All patients remained asymptomatic regardless of eosinophil count. Regarding ACT, there was an increase of 10.9 points, reflecting a switch from very poorly controlled to well controlled asthma. In CARAT, patients shifted from not controlled to controlled, with a global increase of 10.7 points. In mini-AQLQ there was a decrease in the impairment of quality of life and in SNOT-22 it modified from severe to moderate disease, with a mean reduction of 27.8 points. A reduction in the inflammatory profile was observed for exhaled nitric oxide, with a depletion of 53.3ppb. Pulmonary function test at T12 showed a gain of function in all evaluated parameters, regardless of eosinophil count - table II.

Our results suggest that patients with dupilumab-induced eosinophilia often remain asymptomatic regardless of eosinophilia/hypereosinophilia, without any repercussion in both pulmonary function tests and PROMs. A close follow-up is mandatory in these patients, in order to safely maintain dupilumab treatment.