Biomarkers May Identify Patients at Increased Risk for Severe Asthma Exacerbations

This article is part of Pulmonology Advisor‘s coverage of the American Academy of Allergy, Asthma & Immunology, taking place in Orlando, Florida. Our staff will report on medical research related to asthma and other respiratory conditions, conducted by experts in the field. Check back regularly for more news from AAAAI/WAO 2018.

ORLANDO — Fractional exhaled nitric oxide (FeNO), periostin, and eosinophils may be potential biomarkers serving to identify patients at increased risk for severe asthma exacerbations, according to a post hoc analysis of a phase 2b trial presented at the 2018 Joint Congress of the American Academy of Allergy, Asthma & Immunology/World Allergy Organization, held March 2-5, in Orlando, Florida.

Study investigators enrolled adults with uncontrolled persistent asthma despite treatment with medium- to high-dose inhaled corticosteroids and long-acting beta-agonists in a multinational, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT01854047). A total of 776 adults were randomly assigned  1:1:1:1:1 to receive 24 weeks of add-on therapy with subcutaneous dupilumab (200 mg every 2 or 4 weeks each with a loading dose of 400 mg, or 300 mg every 2 or 4 weeks each with a loading dose of 600 mg) or placebo. Participants were then followed for an additional 16 weeks after therapy.  

This post-hoc analysis focused on the placebo cohort of the trial to understand the relationship between severe asthma exacerbation rates and biomarkers related to type 2 inflammation.

The observed annualized rate of severe asthma exacerbations in patients receiving placebo (n=158) were analyzed by the following biomarkers (baseline lowermost vs uppermost quartile [<25th percentile and ≥75th percentile, respectively): FeNO (<16 parts per billion vs ≥48 parts per billion), serum periostin (<67 ng/mL vs ≥111 ng/mL), blood eosinophils (<0.15 giga/L vs ≥0.42 giga/L), and serum immunoglobulin E (<76 kU/L vs ≥436 kU/L).

Subgroups for comparison were defined by biomarker cutoffs: lowermost quartile (<25th percentile), uppermost quartile (≥75th percentile), < median, and ≥ median.

Patients with higher baseline biomarker values (≥75th percentile) had a higher number of mean annualized exacerbation rates compared with patients with lower baseline biomarker values (<25th percentile): FeNO (1.54 vs 0.98), periostin (1.42 vs 0.80), and eosinophils (1.31 vs 0.43). Higher vs lower baseline total serum immunoglobulin E was not as clearly associated with higher exacerbation rates (1.07 vs 0.94).

Patients with higher baseline biomarkers indicative of type 2 inflammation also had a higher number of mean annualized severe exacerbation rates compared with patients with lower baseline biomarkers: FeNO (1.63 vs 0.99), periostin (1.54 vs 0.83), and eosinophils (1.63 vs 0.39). Again, this effect was less clear for immunoglobulin E (1.01 vs 0.83).

“The use of combinations of biomarkers enabled identification of patient subgroups at higher risk of severe asthma exacerbations — particularly patients with higher levels of FeNO at baseline and higher levels of periostin/eosinophils/IgE at baseline,” the researchers concluded.

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Reference

Castro M, Swanson BN, Jayawardena S, et al. Exacerbation risk and type 2 inflammation in placebo patients during a phase 2b study of dupilumab in patients with uncontrolled persistent asthma. Presented at: 2018 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress; March 2-5, 2018; Orlando, FL. Poster 354.