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Baseline FeNO levels predict future exacerbations and response to dupilumab

Published: December 16, 2022

Biomarkers are helpful in treating patients with asthma if they allow the clinician to make a prediction about a patient’s future. They are particularly helpful if they identify the risk of an adverse outcome that could be reduced with treatment. Fractional exhaled nitric oxide, or FeNO, is a biomarker of type 2 inflammation that can be measured using a simple and inexpensive breath test. Dupilumab is a fully humanized monoclonal antibody that blocks the shared receptor components of interleukin-4 and interluekin-13, cytokines that are key and central drivers of type 2 inflammation. The objective of this study was to evaluate the ability of baseline FeNO levels, adjusted for baseline clinical characteristics including blood eosinophil levels, to predict the response to dupilumab in patients with asthma.

In the 52-week, double-blind, placebo-controlled, phase 3 LIBERTY ASTHMA QUEST trial, dupilumab 200 mg and 300 mg every 2 weeks vs placebo reduced severe asthma exacerbations and improved lung function and quality of life in patients 12 and older with uncontrolled, moderate-to-severe asthma. In a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Pavord and colleagues performed a post hoc analysis of the QUEST trial analyzing the rate of severe asthma exacerbations during the 52-week treatment period and the change from baseline in lung function at weeks 12 and 52, as a function of baseline FeNO as a continuous variable, and adjusted for baseline clinical characteristics, including blood eosinophil levels.

In this analysis, elevated levels of FeNO at baseline were associated with an increased risk of an asthma attack in patients who received placebo, and with a larger reduction in asthma attack risk in patients treated with dupilumab. There was evidence that FeNO provided additive value as a prognostic and predictive biomarker, above and beyond that provided by blood eosinophil count, a more well-established asthma biomarker. Together these data support the use of FeNO as a biomarker that predicts future asthma exacerbation risk, as well as the response to dupilumab, independent of eosinophil levels and other clinical characteristics, in patients with uncontrolled moderate-to-severe asthma and evidence of type 2 inflammation.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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