Use of benralizumab led to significant improvements in CT mucus scores and asthma control over 2.5 years, as indicated by data from 29 individuals with eosinophilic asthma.
“Mucus-plug formation in asthma may be driven in whole or in part by eosinophilic oxidation,” write Marrissa J. McIntosh, BSc, of Western University, London, Canada, and colleagues.
Previous studies have shown that a single dose of benralizumab was associated with improved scores on the Asthma Control Questionnaire (ACQ-6), the researchers say.
However, the question of whether eosinophilic depletion clears mucus plugs for patients with eosinophilic asthma had not been addressed, they write.
In a study published in the journal Chest, the researchers used CT and MRI to explore the effect of treatment with benralizumb on mucus plugs and ventilation defects (measured by ventilation defect percent) over a 2.5-year period. The study population included 29 adults aged 18 to 80 years with poorly controlled eosinophilic asthma. The mean age of the patients was approximately 60 years, and more than two thirds were women.
Patients were assessed 28 days after receiving a dose of benralizumab. A total of 16 patients returned for follow-up at 1 year, and 13 returned for follow-up at 2.5 years; the 1-year and 2.5-year visits included imaging, spirometry, and oscillometry.
The mean ACQ-6 score of 2.0 at 28 days post benralizumab significantly improved after 1 year (0.5; P =.02) and 2.5 years (0.5; P = .03).
The mean ventilation defect percent (VDP) change at 2.5-years (-4%) was greater than the minimal clinically important difference, but it was not significantly different in comparison with VDP at 28 days post benralizumab. However, the mucus score significantly improved from approximately 3 to approximately 1 at 2.5 years (P =.03).
At 2.5 years, five patients whose mean mucus count was 11 at baseline showed no CT evidence of mucus plugs. In addition, one patient had two fewer mucus plugs compared to baseline, one had the same number, and four patients with no mucus plugs at baseline still had no mucus plugs. Significant improvements also occurred in asthma control, central airway resistance, quality of life, FEV1, airway lumen area, wall thickness, and total airway count at 2.5 years, the researchers write.
The finding that the mean VDP improvement persisted reflected data from previous studies of benralizumab, they say. “Improved asthma control in response to benralizumab may be mechanistically linked to mucus-occlusions and airway function, both of which appear to be modifiable outcomes.”
The study findings were limited by several factors, including the small sample size and response bias, as only participants with a clinical response who continued treatment were assessed, the researchers note. However, the clinical characteristics of the subgroups at the 1- and 2.5-year follow-ups were not significantly different from those of the 28-day group, they say.
More research is needed, especially on the dynamics of mucus plug formation and dissolution, they write. However, the results suggest that “long-term benralizumab-driven 318 eosinophil depletion results in disrupted airway luminal occlusions and improved airway structure and function,” which may provide future information on disease-modifying activity and may improve patient care, they conclude.
The study was supported by AstraZeneca Canada. Lead author McIntosh is supported by the Natural Sciences and Engineering Research Council of Canada postgraduate doctoral award and a Canadian Respiratory Research Network studentship training award.
Chest. Published February 10, 2023. Full text
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