The Lancet Respiratory Medicine Journal recently published a study on treating eosinophilic exacerbations of asthma and chronic obstructive pulmonary disease (COPD) with benralizumab (ABRA).

COPD and asthma exacerbations significantly contribute to global morbidity and mortality.

While the past 30 years have seen advances in preventing severe asthma and, more recently, COPD exacerbations with monoclonal antibody therapies, progress in acute treatment remains limited.

Systemic glucocorticoids are a cornerstone of exacerbation management, despite adverse events arising in half of patients treated and treatment failure occurring in at least 30% of cases.

Moreover, repeated courses of systemic glucocorticoids are associated with a higher risk of mortality.

About The Study

ABRA was a multicentre, phase 2, double-blind, double-dummy, active placebo-controlled randomised trial completed in the UK at Oxford University Hospitals NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust. 

During acute asthma or COPD exacerbations, adults with blood eosinophil count≥300 cells/μL were randomly assigned (1:1:1) to one of three treatments:

1) prednisolone 30 mg once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA plus PRED group);

2) placebo tablets once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA group);

3) prednisolone 30 mg once daily for 5 days and placebo subcutaneous injection once (PRED group). 

Randomisation was conducted using a centralised interactive computer system, ensuring blinding of patients and study staff to blood results and treatment assignments.

Co-primary outcomes included the proportion of treatment failures over 90 days and total visual analogue scale (VAS) symptoms at day 28 in the pooled benralizumab groups compared with the prednisolone alone group and analysed in the intention-to-treat population. The trial was registered on Clinicaltrials.govNCT04098718.

Findings

Between May 13, 2021, and Feb 5, 2024, 287 patients were screened for study inclusion. Of these, 129 were excluded for not meeting eosinophil criteria or lacking an exacerbation, leaving 158 patients (54% female, 46% male, mean age 57 years, range 18–84) who were randomly assigned at acute eosinophilic exacerbation of asthma or COPD.

Participants were allocated to one of three groups: 53 to PRED, 53 to BENRA, and 52 to BENRA + PRED.

At 90 days, treatment failures occurred in 39 (74%) of 53 in the PRED group, and 47 (45%) of 105 in the pooled-BENRA group (OR 0·26 [95% CI 0·13–0·56]; p=0·0005). 

The 28-day total VAS mean difference was 49 mm (95% CI 14–84; p=0·0065), favouring the pooled-BENRA group. 

Benralizumab was well tolerated, with no fatal adverse events reported. Hyperglycemia and sinusitis-related adverse events were associated only with prednisolone.

Conclusions

Benralizumab can be used as a treatment for acute eosinophilic exacerbations and achieves better outcomes than the current standard of care with prednisolone alone. These results offer a new way of treating eosinophilic endotypes of asthma and COPD exacerbations.

Read the full publication

Reference: 

Ramakrishnan, S., Russell, R. E. K., Mahmood, H. R., Krassowska, K., Melhorn, J., Mwasuku, C., Pavord, I. D., Bermejo-Sanchez, L., Howell, I., Mahdi, M., Peterson, S., Bengtsson, T., & Bafadhel, M. (2025). Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): A double-blind, double-dummy, active placebo-controlled randomised trial. The Lancet Respiratory Medicine, 13(1), 59–68. https://doi.org/10.1016/S2213-2600(24)00123-4

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