FeNO as a Predictor of Response to Dupilumab in Uncontrolled Asthma

Dupilumab demonstrated the greatest clinical benefit in patients with uncontrolled, moderate to severe asthma who had elevated levels of fractional exhaled nitric oxide (FeNO) and blood eosinophils, according to a post hoc analysis presented at the American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting, held virtually from November 13 to 15.

FeNO is a clinically useful biomarker of interleukin (IL)-4/IL-13-mediated airway inflammation, and dupilumab is a fully human monoclonal antibody that blocks a shared receptor component for IL-4/IL-13. Results from the LIBERTY ASTHMA QUEST study (ClinicalTrials.gov Identifier: NCT02414854) demonstrated that dupilumab 200/300 mg reduced severe asthma exacerbations, improved prebronchodilator forced expiratory volume in 1 second (FEV₁), and was generally well tolerated in patients with uncontrolled, moderate to severe asthma compared with placebo.

Researchers performed a post hoc analysis to assess baseline FeNO levels as predictors of response to dupilumab. Patients treated with dupilumab experienced a greater benefit in annualized exacerbation rates and prebronchodilator FEV₁ at week 12 with increasing FeNO. In addition, the magnitude of the decrease in annualized exacerbation rates/improvement in lung function in dupilumab was significantly higher in patients with FeNO more than or equal to 25 ppb than in patients with FeNO less than 25 ppb compared with placebo (treatment-by-subgroup interaction, P <.0001).

In patients with blood eosinophils ≥150 cells/µL, annualized exacerbation rates were significantly reduced in patients who received dupilumab 200/300 mg by 40.3%/66.7% compared with patients who received placebo (P <.001) in patients with FeNO less than or greater than or equal to 25 ppb, whereas prebronchodilator FEV₁ at week 12 was significantly improved in patients with FeNO more than or equal to 25 ppb (0.26 L; P <.0001). Significant differences in patients with FeNO less than 25 ppb were not observed (0.03 L; P =.3248).

“Increasing FeNO was associated with reduced [annualized exacerbation rates] and lung function improvements in dupilumab-treated patients,” the researchers concluded. “Patients with elevated FeNO and [blood eosinophils] showed the greatest clinical benefits.”

Reference

Pavord I, Busse W, Corren J, et al. Baseline exhaled nitric oxide (FENO) as predictor of response to dupilumab in uncontrolled, moderate-to-severe asthma. Presented at: the American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting (Virtual Experience); November 13-15, 2020. Abstract P220.