Response to Dupilumab in Severe Asthma Predicted by Baseline FeNo

The monoclonal antibody dupilumab demonstrated the greatest clinical benefit in asthma patients with severe uncontrolled disease and elevated levels of fractional exhaled nitric oxide (FeNO) and blood eosinophils, according to research presented at the American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting, held virtually from November 13 to 15, 2020.

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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 vs placebo reduced severe asthma exacerbations, improved prebronchodilator (FEV₁), and was generally well tolerated in patients with uncontrolled, moderate to severe asthma. Treatment effects were greater in patients with elevated type 2 biomarkers at baseline ( (blood eosinophils [Eos] ≥150 cells/μL or FeNO ≥25 parts per billion [ppb]).

In this post-hoc analysis, researchers led by Ian Pavord, University of Oxford and Oxford Respiratory NIHR BRC, assessed the additional value of 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 levels. In addition, the magnitude of the decrease in annualized exacerbation rates/improvement in lung function in dupilumab-treated patients was significantly higher in those with FeNO levels ≥25 ppb than in patients with FeNO <25 ppb vs placebo (treatment-by-subgroup interaction, P <.0001).

In patients with Eos ≥150 cells/µL, annualized exacerbation rates were significantly reduced in patients who received dupilumab 200/300 mg by 40.3%/66.7% vs 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 ≥25 ppb (0.26 L; P <.0001). Significant differences in patients with FeNO <25 ppb were not observed (0.03 L; P =.3248).

"Increasing baseline FeNO levels were associated with reduced exacerbation rates and increased lung function improvements in dupilumab-vs placebo-treated patients," the researchers concluded. “Patients with elevated FeNO and [blood eosinophils] showed the greatest clinical benefits.”

The authors point out also that FeNo "can be rapidly and inexpensively assessed during routine clinical assessments at the patient’s point of care, and may be useful in predicting responsiveness to some biological therapies."

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.