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BackgroundFractional exhaled nitric oxide (FeNO) may have a role both as a prognostic and predictive biomarker, in combination with eosinophils, for assessing responsiveness to some biological therapies.ObjectiveWe evaluated the value of baseline FeNO, adjusted for baseline blood eosinophil levels and other clinical characteristics, as an independent predictor of treatment response to dupilumab in patients with uncontrolled, moderate-to-severe asthma.MethodsWe performed a post-hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854), a phase 3, double-blind study in patients aged ≥ 12 years with uncontrolled moderate-to-severe asthma who received dupilumab 200/300 mg, or placebo every 2 weeks up to 52 weeks. Annualized event rate (AER) of severe exacerbations and least squares mean change from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV1) at weeks 12 and 52 were assessed in relationship to baseline FeNO, adjusted for eosinophils and other clinical characteristics.ResultsAER increased with increasing baseline FeNO in placebo, and decreased in dupilumab groups. The relative risk of severe exacerbations was 22·7%, 58·3%, and 69·3% lower for dupilumab vs placebo for the FeNO < 25, 25 to < 50, and ≥ 50 ppb subgroups. The magnitude of FEV1 improvement increased with higher baseline FeNO for dupilumab and was consistent across the continuum of FeNO levels in placebo. Both findings were independent of blood eosinophil levels. Significant differences were observed between FeNO subgroups.ConclusionIncreased baseline FeNO was associated with greater clinical effects in dupilumab vs placebo, independent of eosinophil levels and other clinical characteristics.

Original publication

DOI

10.1016/j.jaip.2022.11.043

Type

Journal article

Journal

The journal of allergy and clinical immunology. In practice

Publication Date

12/2022

Addresses

University of Oxford and Oxford Respiratory NIHR BRC, Oxford, UK. Electronic address: ian.pavord@ndm.ox.ac.uk.