Baseline FeNO Independently Predicts the Dupilumab Response in Patients With Moderate-to-Severe Asthma.

ABSTRACT

BACKGROUND: FeNO may have a role as both a prognostic and predictive biomarker in combination with eosinophils for assessing responsiveness to some biological therapies. OBJECTIVE: We 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. METHODS: We performed a post hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854), a phase 3, double-blind study in patients aged 12 years and older with uncontrolled moderate-to-severe asthma, who received dupilumab 200 or 300 mg, or placebo every 2 weeks up to 52 weeks. We assessed the annualized event rate of severe exacerbations and least-squares mean change from baseline in prebronchodilator FEV1 at weeks 12 and 52 in relationship to baseline FeNO, adjusted for eosinophils and other clinical characteristics. RESULTS: The annualized event rate 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 versus placebo for the FeNO less than 25, 25 to less than 50, and 50 and greater parts per billion 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. CONCLUSIONS: Increased baseline FeNO was associated with greater clinical effects in dupilumab versus placebo independently of eosinophil levels and other clinical characteristics.