A single injection of benralizumab, with or without oral prednisolone, significantly reduced treatment failures and improved symptoms in patients experiencing eosinophilic exacerbations of asthma or chronic obstructive pulmonary disease, according to a phase 2 trial published in The Lancet Respiratory Medicine.
The Acute exacerbations treated with BenRAlizumab trial found that patients receiving benralizumab had significantly lower odds of treatment failure within 90 days compared to those receiving standard prednisolone therapy alone. The number needed to treat was 4 patients to prevent one treatment failure.
The double-blind, double-dummy study enrolled 158 patients (86 [54%] female, 72 [46%] male; mean age 57 years, range 18-84) across two UK hospitals between May 2021 and February 2024. Of these, 88 (56%) had asthma, 51 (32%) had COPD, and 19 (12%) had both conditions. Participants had blood eosinophil counts ≥300 cells/µL during an acute exacerbation. They were randomized to receive either: prednisolone 30 mg daily for 5 days plus placebo injection (53 patients); benralizumab 100 mg subcutaneous injection plus placebo tablets (53 patients); or combination therapy with both active treatments (52 patients).
Treatment failures occurred in 74% of patients receiving prednisolone alone compared to 45% in the pooled benralizumab groups. Additionally, the benralizumab groups showed greater improvement in respiratory symptoms at 28 days based on visual analogue scale scores (mean difference 49 mm).
"These results offer a new way of treating eosinophilic endotypes of asthma and COPD exacerbations," said lead author Sanjay Ramakrishnan, MBBS, of the Institute for Respiratory Health at the University of Western Australia.
The study represents the first successful trial targeting the eosinophilic inflammatory pathway during acute exacerbations. Previous attempts using biological therapies for acute exacerbations had failed, likely because they did not select patients based on inflammatory endotype.
A total of 324 adverse events occurred in 128 patients: 129 events in 48 (91%) prednisolone group patients, 95 events in 41 (77%) benralizumab group patients, and 100 events in 39 (75%) combination group patients. Events related to prednisolone, including hyperglycemia and sinusitis, only occurred in groups receiving oral corticosteroids. No fatal adverse events were reported.
The researchers acknowledged study limitations, including that only 13% of participants were recruited from emergency departments. They suggested future research should examine benralizumab's efficacy in more severe exacerbations requiring hospitalization.
Conflict of interest disclosures can be found in the study.
