High Blood Eosinophils and FeNO Levels Predict Better Dupilumab Response in Moderate-to-Severe Asthma
核心洞察
Post-hoc analysis of LIBERTY ASTHMA (搜索) QUEST trial reveals patients with elevated blood eosinophils and FeNO levels show significantly higher odds of achieving clinical remission with dupilumab treatment.
Clinical remission, defined by four criteria including no exacerbations, no symptoms, no oral corticosteroids, and stable lung function, was achieved in 38.3% of dupilumab-treated patients versus 26.2% in placebo group.
Patients with blood eosinophil counts ≥150 cells/µL and FeNO levels ≥20 ppb showed the strongest response to dupilumab, with adjusted odds ratio of 2.63 for achieving clinical remission.
A groundbreaking post-hoc analysis of the 52-week phase 3 LIBERTY ASTHMA (搜索) QUEST study has identified key baseline factors that significantly influence the likelihood of achieving clinical remission with dupilumab in moderate to severe asthma patients. The findings, presented at the 2025 American Academy of Allergy, Asthma and Immunology/World Allergy Organization Joint Congress in San Diego, offer valuable insights for predicting treatment response.
Key Baseline Predictors of Response
The study analyzed 1,530 patients, with 1,011 receiving dupilumab (200mg/300mg every 2 weeks) and 519 receiving placebo. Researchers found that higher baseline blood eosinophil counts substantially increased the odds of achieving clinical remission with dupilumab treatment. The effect was particularly pronounced in patients with counts ≥500 cells/µL, who showed an adjusted odds ratio (aOR) of 4.04 (95% CI, 2.45-6.68; P < .0001).
Elevated fractional exhaled nitric oxide (FeNO) levels also proved to be a significant predictor. Patients with baseline FeNO levels ≥20 ppb demonstrated significantly higher odds of achieving remission (aOR = 2.35; 95% CI, 1.74-3.16; P < .0001).
Clinical Remission Outcomes
The study introduced a novel multicriteria approach to evaluate treatment efficacy, defining clinical remission through four specific parameters:
- Absence of asthma exacerbations
- No symptoms (ACQ-5 score <1.5)
- No oral corticosteroid use
- Stable or improved lung function at 12 months
Using these criteria, 38.3% of dupilumab-treated patients achieved clinical remission compared to 26.2% in the placebo group. The most robust response was observed in patients who had both elevated blood eosinophils (≥150 cells/µL) and FeNO levels (≥20 ppb), with an aOR of 2.63 (95% CI, 1.88-3.66; P < .0001).
Impact of Baseline Lung Function
Baseline pre-bronchodilator FEV1 also influenced treatment outcomes. Patients receiving dupilumab showed improved odds of achieving remission regardless of their baseline FEV1, though the effect was slightly stronger in those with FEV1 ≤1.75 L (aOR = 1.9; P = .0002) compared to those with FEV1 >1.75 L (aOR = 1.61; P = .0051).
Future Implications
"This is first evidence of dupilumab reaching 'clinical remission,' an innovative multicriteria tool to evaluate efficacy of a treatment in severe asthma (搜索)," stated Giorgio Walter Canonica, FERS, FEAACI, FAAAAI, FACAAI, professor at Humanitas University (搜索). He emphasized that this comprehensive approach to evaluating treatment success could become the primary outcome measure in future severe asthma trials, following a trend already established in other chronic diseases such as ulcerative colitis (搜索).
The findings represent a significant advancement in personalizing asthma (搜索) treatment, potentially allowing clinicians to better identify patients who are most likely to achieve optimal outcomes with dupilumab therapy.