The ARIETTA study reveals potential biomarkers for severe asthma
Published online: April 15, 2020
Asthma is one of the most common chronic airway diseases and affects both adults and children. The increased availability of specific treatments for severe asthma has highlighted the importance of, and need for, reliable measures that can be used for patient selection, disease monitoring and the identification of patients at greatest risk from acute attacks. An important characteristic of asthma is Type 2 inflammation, which occurs in many patients and can be characterized by several different features. These include periostin, a protein that is released by inflammatory cells into the blood and can be found in lung tissues and cells; eosinophils, a subpopulation of white blood cells; allergen-specific antibodies (immunoglobulin E; IgE); and exhaled nitric oxide (FeNo). As a result, these are frequently used as biomarkers for both asthma research and patient disease management. Currently, the 2020 Global Initiative for Asthma (GINA) recommends the use of specific treatments for patients with severe asthma with Type 2 inflammation (Type-2 high) who meet at least one of the following criteria: blood eosinophil levels ≥ 150 cells per microliter (µL), exhaled FeNO ≥ 20 parts per billion (ppb), and/or non-seasonal allergy. However, although these Type 2 biomarkers are being increasingly used to select patients for treatment, it is not yet known how accurately they can identify, or predict, patients at risk for asthma attacks in the clinical setting.
The ARIETTA study observed adult patients (≥ 18 years old) with severe asthma over a period of 1 year to explore periostin and other Type 2 inflammatory biomarkers and how they linked with clinical measures. Patients with severe asthma as defined by GINA, who were receiving standard of care treatments (daily inhaled corticosteroids and ≥ 1 second controller medication or oral corticosteroids) were enrolled. Patients could not participate if they had reported an asthma attack in the 6 weeks before the start of the study or had been treated with other antibody-therapies in the 6 months prior. The primary goal of the study was to determine the number of asthma attacks over one year (rate) in patients who were periostin-high (≥ 50 ng/mL) versus periostin-low (< 50 ng/mL) at the start of the study. This study also evaluated the time to first asthma attack, changes in quality of life, change in the volume of air exhaled (forced exhalation volume; FEV1), FeNO levels and standard safety measures. Asthma biomarkers, including periostin, blood eosinophils, IgE, and FeNO, were monitored throughout the study. However, during the course of the ARIETTA study, findings from another asthma trial became available, which led to stopping ARIETTA before all the planned patients could be recruited. As such, the findings reported by Buhl et al in The Journal of Allergy and Clinical Immunology: In Practice show an overview of patient data at the time the study was stopped.
A total of 465 patients from 84 sites across 13 countries were analyzed prior to stopping the study. Patients were on average 53 years old, 66% were female, 42% reported at least one asthma attack within the last year, and 52% were categorized as periostin-high. Similar attack rates were seen over 1 year in periostin-high and periostin-low patients (0.47 vs 0.51 attacks per year for each group). Similarly, there was no clinically relevant difference in FEV1, FeNO levels, or quality-of-life measures between the periostin groups. Taken together, these data suggest that periostin alone might not be an ideal biomarker to identify patients at risk for asthma attacks. However, further exploratory analysis revealed a trend of higher attack rates in patients with increased blood eosinophil counts (≥ 300 cells per uL), higher FeNO levels (≥ 25 ppb), or both, compared with patients who had lower levels. These additional findings suggest that Type 2 biomarkers, such as blood eosinophil count and exhaled FeNO, may be clinically relevant indicators of increased risk of attacks in patients with severe asthma. Further studies will be needed to confirm these findings.
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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