Dupilumab Reduces Exacerbations Independent of Changes in Biomarkers in Moderate-to-Severe Asthma

Ian D Pavord; Thomas B Casale; Jonathan Corren; Mark J FitzGerald; Yamo Deniz; Arman Altincatal; Rebecca Gall; Nami Pandit-Abid; Amr Radwan; Juby A Jacob-Nara; Paul J Rowe; William W Busse

doi:10.1016/j.jaip.2024.03.031

Dupilumab Reduces Exacerbations Independent of Changes in Biomarkers in Moderate-to-Severe Asthma

J Allergy Clin Immunol Pract. 2024 Mar 29:S2213-2198(24)00306-4. doi: 10.1016/j.jaip.2024.03.031. Online ahead of print.

Authors

Affiliations

¹ NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom. Electronic address: ian.pavord@ndm.ox.ac.uk.
² Division of Allergy and Immunology, University of South Florida, Tampa, Fla.
³ David Geffen School of Medicine, University of California, Los Angeles, CA.
⁴ University of British Columbia, Vancouver, BC, Canada.
⁵ Regeneron Pharmaceuticals, Inc, Tarrytown, NY.
⁶ Sanofi, Cambridge, Mass.
⁷ Sanofi, Bridgewater, NJ.
⁸ UW Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

PMID: 38555079
DOI: 10.1016/j.jaip.2024.03.031

Abstract

Background: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma.

Objective: This post hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854).

Methods: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV₁) at week 52 were performed as a function of the fold change in FeNO at week 52 and the maximum fold change in Eos over weeks 0-12 (also change from baseline in pre-BD FEV₁ at week 12).

Results: The combined placebo and dupilumab groups comprised 638 and 1264 patients, respectively. FeNO levels declined rapidly by week 2 and then gradually to week 52 in patients treated with dupilumab versus placebo; Eos, after initially increasing with dupilumab, declined slightly from baseline in both treatment groups. AER during QUEST showed no significant association with the change in biomarkers in either treatment group. The change from baseline in pre-BD FEV₁ at week 52 was inversely associated with the fold change in FeNO in both groups, with a significant difference between the dupilumab and placebo curves (P = .014), and was positively associated with the fold change in Eos in both groups (P = .022).

Conclusions: Relative changes in FeNO and Eos were not associated with AER, regardless of treatment arm. However, changes in both biomarkers showed a predictive value for lung function improvement; for FeNO, this was specific to the dupilumab treatment arm.

Keywords: Eosinophils; Exacerbations; Fractional exhaled nitric oxide; Lung function.

Associated data

ClinicalTrials.gov/NCT02414854