Benralizumab appears superior to mepolizumab in severe eosinophilic asthma

Both mepolizumab and benralizumab are effective in improving the clinical outcomes of patients with severe eosinophilic asthma, as shown in a recent study. However, treatment with benralizumab appears to be better than mepolizumab in reducing exacerbations, improving forced expiratory volume, and depleting blood eosinophils.

“Mepolizumab and benralizumab have revolutionized severe asthma treatment,” the researchers said. “As this study demonstrates, these treatments are highly effective in reducing exacerbation frequency, the need for maintenance oral steroids, and reducing the burden of asthmatic symptoms.”

Data from patients in two large tertiary care severe asthma clinics were prospectively collected at baseline and at 6 and 12 months following treatment initiation. Of the 204 patients included, 117 received mepolizumab and 87 benralizumab.

Baseline characteristics, such as age, gender, body mass index, steroid dose, and blood eosinophil count, were similar between the two treatment groups. However, patients in the mepolizumab arm had a higher Asthma Control Questionnaire (ACQ) at baseline (4.0 vs 3.6; p=0.018), as well as more frequent reliever medication usage and lower prebronchodilator FEV1% (56.0 vs 63.8; p=0.008).

After 6 months, both groups showed significant improvements in ACQ (2.3; p<0.001), oral steroid requiring exacerbations (incident rate ratio, 0.26, 95 percent confidence interval [CI], 0.18‒0.37; p<0.001), and FEV1. [Respirology 2023;28:1117-1125]

However, benralizumab resulted in 0.18-litre (95 percent CI, 0.05‒0.30) greater improvement in FEV1 than mepolizumab (p=0.002) even when adjusting statistically for baseline differences between groups.

“These differences were even more pronounced at 12 months post-treatment initiation, when the improvement in exacerbation frequency with benralizumab was 64-percent greater than with mepolizumab (p=0.01),” the researchers said.

More effective

Although both treatments were effective at significantly lower blood eosinophil count at 6 and 12 months, such benefit was markedly greater with benralizumab (‒260 cells/μL; p=0.001).

“A clinician might question whether there was anything to choose between these two effective treatments, or whether they were equivalent. There are no direct head-to-head comparisons in randomized controlled trials to provide guidance,” the researchers said.

“However, the data from this study suggests that benralizumab may be substantially more effective at reducing exacerbations (twice as effective compared with mepolizumab), and substantially more effective at improving lung function (180 mL greater with benralizumab compared to mepolizumab). These would be impressive differences if verified in subsequent studies,” they added.

In addition, an earlier study reported that benralizumab had been used successfully in patients with suboptimal response to mepolizumab. [Allergy 2021;76:1890-1893]

“Since it has been established that the higher the peripheral blood eosinophil count, the greater the risk of asthma exacerbation, it seems likely that a treatment which causes greater reduction in the eosinophil count will be more effective at reducing exacerbation frequency,” the researchers said. [Allergy 2021;76:1890-1893]

The current study was limited by its observational design and the lack of randomization at the outset, leading to variations in the baseline characteristics of the two treatment groups. Specifically, the mepolizumab group might have been a more severe cohort with greater baseline ACQ and lower baseline FEV1 than those in the benralizumab group.

“It is possible that this may have contributed to an inferior response to mepolizumab in relation to exacerbation frequency and FEV1,” the researchers said.