Dupilumab reduces asthma exacerbations in patients with asthma regardless of changes in markers of type 2 inflammation
Published: March 28, 2024
Patients with asthma have higher levels of nitric oxide in their breath than healthy people. The amount of nitric oxide in a person’s exhaled air (called fractional exhaled nitric oxide, or FeNO) is a measure of type 2 lung inflammation and may be a useful signal (also known as a biomarker) for predicting the risk of future asthma exacerbations as well as response to therapy. Dupilumab is a monoclonal antibody that inhibits both interleukin 4 and 13, key proteins driving type 2 inflammation in asthma and other inflammatory diseases. In a previous analysis of the phase 3 LIBERTY ASTHMA QUEST clinical trial, FeNO was found to be a more important biomarker than blood eosinophils for predicting future exacerbation risk. Additionally, patients with higher FeNO levels at the start of the study had greater treatment benefits from dupilumab even after taking differences in blood eosinophil levels and other clinical characteristics into account.
In a recent study in The Journal of Allergy and Clinical Immunology: In Practice, Pavord et al. further explored the relationship between changes in FeNO or blood eosinophils and treatment outcomes (exacerbation rate and lung function) during treatment with dupilumab in the QUEST clinical trial. In QUEST, patients 12 years or older received dupilumab 200 mg or 300 mg or a matched placebo every 2 weeks for 52 weeks. For the current analysis, data from the two dupilumab groups and two placebo groups were combined.
In total, 638 patients were included in the combined placebo group and 1,264 in the combined dupilumab group. The mean age was 48 years in both groups, and 65% of placebo recipients and 62% of dupilumab recipients were female. In the group who received dupilumab, FeNO levels rapidly decreased in the first 2 weeks of the study and then decreased gradually through to the end of the study at Week 52. FeNO levels in the placebo group did not change significantly during the study. Blood eosinophils increased in the first 8 weeks in the dupilumab group but not in the placebo group, and then decreased gradually in both groups through to the end of the study. No clear relationship between exacerbation rate and changes in FeNO or blood eosinophil levels was seen in the study. However, in the dupilumab group, improvement in lung function, measured using pre-bronchodilator forced expiratory volume in one second (the amount of air one can blow out in one second without using a bronchodilator also known as FEV1), was greater in patients with greater reductions in FeNO during the study (P = 0.014). Improvements in pre-bronchodilator FEV1 were also associated with greater changes in blood eosinophil levels in both groups (P = 0.022).
The authors concluded that dupilumab is effective at reducing the risk of exacerbations in patients with moderate to severe asthma, irrespective of changes in FeNO and blood eosinophils. In addition, reductions in FeNO while receiving dupilumab may help to predict the level of lung function improvement during treatment.
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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