Dupilumab-induced increases in mean eosinophil counts were shown to wane over time in patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and atopic dermatitis (AD), with incidence of eosinophilia not shown to reduce efficacy of the biologic.
Transient increases in mean eosinophil counts observed with dupilumab treatment were shown to wane over time in patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and atopic dermatitis (AD), with incidence of eosinophilia not shown to reduce efficacy of the biologic. Study findings were published in The Journal of Allergy and Clinical Immunology: In Practice.
Currently approved for the treatment of the type 2 inflammatory diseases AD, asthma, CRSwNP, and eosinophilic esophagitis (EoE), dupilumab, a fully human monoclonal antibody that blocks 2 key and central drivers of type 2 inflammation, interleukin (IL)-4 and IL-13, has been shown in clinical trials to cause transient increases in eosinophil counts. Incidence of drug-induced eosinophilia has been associated with several adverse events, including eosinophil-induced organ damage.
“These generally occurred in the first few weeks and returned to baseline or lower by the end of the treatment period,” noted researchers.
They conducted a post-hoc analysis of 11 clinical trials of dupilumab in patients with the type 2 inflammatory diseases:
A total of 6642 patients with asthma (n = 2876), CRSwNP (n = 574), AD (n = 3145), and EoE (n = 47) were assessed for the effect of dupilumab on blood eosinophil counts over time, rates of eosinophilia-related treatment-emergent adverse events (TEAEs) or treatment-emergent eosinophilia (> 1500 cells/mcL), discontinuations, clinical symptoms, and treatment efficacy.
Findings showed that transient increases in mean eosinophil counts occurred in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/mcL; week 4: 515-578 cells/mcL), CRSwNP (baseline: 440-448 cells/mcL; week 16: 595 cells/mcL), and AD (baseline: 434-600 cells/mcL; week 4: 410-710 cells/mcL), which declined starting in week 24 to the baseline level or below—similar to that found in prior research. No increases in mean eosinophil counts were observed in patients with EoE (baseline: 310 cells/mcL; week 4: 230 cells/mcL).
Rates of eosinophilia TEAEs in dupilumab-treated patients across the study cohort ranged from 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare and only occurred in patients with asthma or CRSwNP (7 of 4666 dupilumab-treated patients, including 6 cases of eosinophilic granulomatosis with polyangiitis).
Eosinophilia was not associated with reduced dupilumab efficacy, although researchers noted that group sizes for eosinophilia TEAEs were too small to make robust conclusions.
“Transient increases in eosinophil counts with dupilumab treatment did not impact efficacy and were rarely of clinical consequence. It remains important for physicians to base judgement on individual patient history and baseline eosinophil counts and be alert to hypereosinophilic symptoms,” they concluded.
Wechsler ME, Klion AD, Paggiaro P, et al. Effect of dupilumab on blood eosinophil counts in patients with asthma, chronic rhinosinusitis with nasal polyps, atopic dermatitis, or eosinophilic esophagitis. J Allergy Clin Immunol Pract. Publilshed online May 27, 2022. doi:10.1016/j.jaip.2022.05.019