In patients with uncontrolled asthma, 129Xe magnetic resonance imaging (XeMRI) detected significant improvement in airway dysfunction, as measured by change in ventilation defect percent (VDP), 28 days after an initial dose of benralizumab. Additionally, pretreatment XeMRI VDP and computed tomography (CT) mucus score were predictive of treatment response 28 days after benralizumab initiation. These were among findings of an open-label, single-arm, Canadian pilot study (ClinicalTrials.gov Identifier: NCT03733535) recently published in the journal Chest.
Recognizing that XeMRI VDP offers unique information with respect to asthma control, study researchers sought to determine whether XeMRI could detect airway functional responses to eosinophil depletion following a single dose of benralizumab. They also examined whether airway mucus occlusions mediated this response.
A total of 29 participants (20 female, 9 male) between 18 to 80 years of age (mean age 59±12 years) were included in the pilot study. Of those, 27 had thoracic x-ray computed tomography (CT) results available at baseline and after 28 days. All of the participants underwent MRI, spirometry, and oscillometry testing. In addition, patients’ eosinophil counts were measured and asthma control was determined via Asthma Control Questionnaire (AQL), Asthma Quality of Life Questionnaire (AQLQL), and St. George’s Respiratory Questionnaire assessments. These were completed on day 0 and again on day 28 following a single 30-mg subcutaneously (SC) administered dose of benralizumab. On day 0, CT mucus plugs were scored; MRI VDP was quantified on days 0 and 28.
The investigators found that 28 days after administration of a single dose of benralizumab, participants showed significantly improved blood eosinophil counts, VDP, ACQ-6, and AQLQ (P <.001 for all). Participants also showed significantly improved peripheral (R5-19Hz) airways resistance, but not central airways resistance or reactance (P =.04).
Further, on day 28, significantly improved VDP and ACQ-6 were also found in the subgroup of 9 patients with 5 or more mucus plugs, but not in the subgroup of 18 participants with less than 5 mucus plugs.
Per univariate relationships for change in ACQ-6, multivariable models were produced, which demonstrated that day 0 VDP and day 0 CT mucus scores were significant variables for change in ACQ-6 on day 28 following treatment with a single dose of benralizumab 30 mg SC.
Limitations of this current study included its open-label design and its small sample size, composed primarily of women who were older.
The researchers said their study was the first to show that, among patients with poorly controlled asthma, XeMRI ventilation defects and CT mucus scores measured prior to treatment could help to explain the significantly improved asthma control reported following a single dose of benralizumab. The investigators further noted that their findings suggested that “the mechanism of action of benralizumab may involve the peripheral airways, even in patients with substantial mucus plugging.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
McIntosh MJ, Kooner HK, Eddy RL, et al. Asthma control, airway mucus and 129Xe MRI ventilation after a single benralizumab dose. Chest. Published online March 10, 2022. doi:10.1016/j.chest.2022.03.003