Patients with atopic conditions experience transient eosinophil increases with dupilumab

Patients with asthma, chronic rhinosinusitis with nasal polyps and atopic dermatitis experienced transient increases in eosinophil counts following treatment with dupilumab, according to study results.

However, these increases mostly were not associated with clinical symptoms or sequalae, nor did they have any observable impact on treatment efficacy, Michael E. Wechsler, MD, MMSc, a pulmonologist at National Jewish Health in Denver, and colleagues wrote in the study, published in The Journal of Allergy and Clinical Immunology: In Practice.

The researchers conducted a post-hoc analysis of 11 clinical trials of dupilumab (Dupixent, Sanofi Genzyme/Regeneron) among 6,642 patients, including 2,876 adults and adolescents with moderate to severe or severe corticosteroid-dependent asthma, 574 adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP), 3,145 adults with moderate to severe atopic dermatitis and 47 adults with active eosinophilic esophagitis (EoE).

Researchers of these studies assessed absolute blood eosinophil counts at baseline and throughout their treatment periods. They also recorded eosinophilia treatment-emergent adverse events, clinical symptoms and treatment efficacy.

Median, mean eosinophil counts

Among the patients with asthma, the median blood eosinophil counts appeared relatively unchanged by treatment in two studies, although median eosinophil counts showed a clear elevation in the dupilumab group in a third study (median, 470 cells/µL at week 24 vs. 280 cells/µL at baseline).

Further, researchers observed transient increases in mean eosinophil counts in the dupilumab groups, but not in the placebo groups, in all the asthma studies, with a mean range of 349 cells/µL to 370 cells/µL at baseline and 515 cells/µL to 578 cells/µL at week 4. But these elevated counts generally fell after approximately week 24 in the studies that ran that long.

Median eosinophil counts also remained relatively unchanged in two studies of patients with CRSwNP. However, they again observed a slight increase in mean counts, with 440 cells/µL to 448 cells/µL at baseline and 595 cells/µL at week 16. In one of these studies, eosinophil counts fell to 374.6 cells/µL by week 52.

The researchers observed a slight rise in mean eosinophils from 434 cells/µL to 600 cells/µL at baseline to 410 cells/µL to 710 cells/µL at week 4 among patients with AD in four studies, with declines to baseline and below starting by week 24.

Patients with EoE taking dupilumab did not experience any increases in eosinophil counts, with mean levels of 310 cells/µL at baseline, 230 cells/µL at week 4 and 170 cells/µL at week 12.

Adverse events

The researchers noted 161 eosinophilia treatment-emergent adverse events — with overall rates ranging from 0% to 13.6% among dupilumab-treated patients across the studies — and 22 eosinophilia severe adverse events (range of rates across studies in dupilumab-treated patients, 0%-1.9%).

Excluding patients undergoing oral corticosteroid reduction, 0% to 4.1% of the dupilumab-treated patients and 0% to 1.5% of the patients assigned placebo across all studies experienced eosinophilia treatment-emergent adverse events, mostly of mild to moderate severity.

Only seven of 4,666 patients treated with dupilumab experienced eosinophilia associated with clinical symptoms, including six cases of eosinophilic granulomatosis with polyangiitis among patients with asthma or CRSwNP.

Patients with asthma whose eosinophil counts were greater than 1,500 cells/µL or who experienced eosinophilia treatment-emergent adverse events generally had higher exacerbation rates and higher changes from baseline in their pre-bronchodilator FEV1 than those in intention-to-treat populations. There were lower rates of asthma exacerbations among patients on dupilumab in three of the studies.

Overall, the researchers said they found no meaningful evidence of reduced efficacy of dupilumab among patients with eosinophilia, though they did caution that the group sizes for eosinophilia treatment-emergent adverse events were too small for robust conclusions.

The researchers additionally called for further studies to delineate the mechanisms behind dupilumab’s effect on eosinophil levels and why these responses differ between patients with airway diseases and those with AD.

Clinicians should then base their judgments on individual patient histories and baseline eosinophil counts, the researchers continued, as patients who have higher eosinophil levels at baseline may be at greater risk for developing transient eosinophilia.