Biomarkers predict effectiveness of dupilumab treatment for moderate to severe asthma
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Key takeaways:
- Dupilumab significantly reduced exacerbations and improved lung function among patients with type 2 biomarkers meeting or surpassing Global Initiative for Asthma thresholds.
- Allergic status had no effect on the efficacy of treatment.
- Pretreatment measurements of these biomarkers may be better predictors of treatment benefits than allergy testing.
Elevated baseline levels of type 2 biomarkers predicted improved lung function and reduced exacerbation rates with dupilumab among patients with asthma, according to a study in The Journal of Allergy and Clinical Immunology: In Practice.
Treatment achieved these results regardless of whether patients met guidelines for allergic asthma, Klaus F. Rabe, MD, PhD, professor of pneumology at Christian-Albrechts-Universität in Kiel, Germany, and director of the German Center for Lung Research, Airway Research Center North, and medical director of LungenClinic Grosshansdorf, both in Grosshansdorf, Germany, and colleagues wrote.
The Global Initiative for Asthma (GINA) defines type 2 inflammation as blood eosinophil counts of 150 cells/µL or greater, fractional exhaled nitric oxide counts of 20 ppb or greater, or allergic asthma. The researchers defined allergic asthma as a baseline serum total IgE of 30 IU/mL or higher and one or more perennial aeroallergen-specific IgE levels of 0.35 kU/L or higher.
When patients with type 2 inflammation cannot control their asthma with high-dose inhaled corticosteroids (ICS), GINA guidelines suggest that the use of add-on biologics such as dupilumab (Dupixent, Sanofi Genzyme/Regeneron) should be considered.
The phase 3 LIBERTY ASTHMA QUEST study involved 1,902 patients aged 12 years and older with moderate to severe asthma who received 200 mg or 300 mg of add-on dupilumab or a matched placebo every 2 weeks for 52 weeks.
According to the researchers, 71.4% had blood eosinophil counts meeting or exceeding 150 cells/µL, 60.4% had FeNO of 20 ppb or higher and 56.9% had allergic asthma. Overall, 83.3% had elevated blood eosinophils or FeNO at baseline, and 91.7% had elevated eosinophils or FeNO or allergic asthma.
Among patients with allergic asthma, those treated with dupilumab had fewer severe exacerbations and greater improvements in prebronchodilator FEV1 than those treated with placebo. In fact, exacerbation rates increased with increasing baseline levels of blood eosinophils, FeNO or total serum IgE among patients with allergic asthma treated with placebo but not for those treated with dupilumab.
Annualized exacerbation rates fell with dupilumab treatment regardless of allergic asthma status for those patients with blood eosinophil counts of 150 cells/µL or greater (allergic asthma, 48.9%; placebo, 0.957; dupilumab, 0.489; nonallergic asthma, 67.3%; placebo, 1.123; dupilumab, 0.367), those with FeNO of 20 ppb or higher (allergic asthma, 55.7%; placebo, 0.929; dupilumab, 0.412; nonallergic asthma, 67.5%; placebo, 1.131; dupilumab, 0.368) and those with type 2 inflammatory asthma phenotypes (allergic asthma, 48.8%; placebo, 0.912; dupilumab, 0.467; nonallergic asthma, 64%; placebo, 1.077; dupilumab, 0.388).I
Furthermore, the presence of allergic asthma did not impact the efficacy of dupilumab in improving prebronchodilator and postbronchodilator FEV1 in patients with elevated type 2 biomarkers at study baseline.
Treatment with dupilumab led to significant increases in postbronchodilator FEV1 at every time point in the study, the researchers continued, regardless of whether patients met criteria for allergic asthma compared with placebo.
Overall, dupilumab significantly reduced rates of severe exacerbations and improved lung function among patients with a type 2 inflammatory asthma phenotype, although allergic status had no impact on outcomes.
As a result, the researchers concluded that blood eosinophil and FeNO levels may be better predictors of the benefits of dupilumab treatment for moderate to severe asthma than allergy testing.
Perspective
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These results are not surprising. Because it binds the IL-4 receptor that blocks both IL-4 and IL-13, dupilumab is known to work well in type 2 inflammatory patients with severe asthma. Whether a patient is allergic or not, dupilumab is expected to work well among patients who have either increased eosinophils or increased exhaled nitric oxide or both. This can occur in conjunction with or independent of allergic status.
These findings also are consistent with my prior clinical experience. Dupilumab works well independently of allergic status. Doctors should consider measuring these biomarkers, eosinophils and exhaled nitric oxide in all patients with moderate to severe asthma so they can get a more personalized, precision-based approach.
Next, researchers should compare these results with other biologics. They also should evaluate data in nonallergic asthma and consider evaluating dupilumab’s efficacy regarding airway hyper-responsiveness.
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