Benralizumab Significantly Improves Mannitol Airway Hyper-responsiveness

Rory Chan, PhD

A new investigation into benralizumab found that the therapy significantly improved mannitol airway hyperresponsiveness (AHR) and led to better asthma control and quality of life in affected patients.

The findings were presented at the American Thoracic Society 2020 International Conference in San Francisco.

In their written abstract, investigators led by Rory Chan, PhD, of the University of Dundee School of Medicine, UK, cited AHR as “a hallmark of persistent asthma”, noting that it could also be assessed via indirect challenge with mannitol.

With their study, Chan and colleagues sought to determine the affect of the anti-IL5ra monoclonal antibody benralizumab on AHA, which is currently unknown.

Following an initial 4 week run-in period with usual inhaled corticosteroid (ICS) and LABA treatment at baseline, the team administered 3 doses of open label benralizumab 30mg for 4 weeks in addition to usual therapy in adult patients with severe eosinophilic asthma.

The primary endpoint was the doubling dose (DD) change in mannitol sensitivity as PD10 FEV1 after 12 weeks compared to baseline. This was powered at 90% with 18 patients to detect a 1 DD difference.

Meanwhile, key secondary outcomes included mannitol reactivity as response dose ratio (RDR), spirometry, oscillometry, ACQ-6, mini-AQLQ, peripheral blood eosinophils (PBE) and FeNO.

Among the 19 patients included in the study, the mean age was 53 years and the mean ICS dose was 1884µg. Meanwhile, 11 patients were currently being treating with LAMA.

Investigators found that benralizumab significantly improved mannitol PD10 by 1.7 DD (95%CI 0.7 to 2.8) (P=0.004), as well as significantly improved mannitol RDR, PBE, ACQ and mini-AQLQ by week 12.

Notably, significant attenuation of mannitol AHR was dissociated form a lack of improvement across all lung function outcomes.

Investigators also noted that 10 patients experienced an improvement in PD10 that exceeded ≥1.0 DD. Meanwhile, 18 and 15 patients respectively experienced ACQ and AQLQ improvements which exceeded the MCID ≥0.5 units, and increased FeNO over the 12 week period suggested to investigators that ICS adherence was “unlikely”.

“Benra significantly improved mannitol AHR, in conjunction with better asthma control and quality of life,” the team wrote. “The disconnect between improvements in AHR but not airway calibre infers an anti-inflammatory action due to eosinophil depletion.”