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Monoclonal antibodies effective in eosinophilic asthma

Retrospective real-world data confirms the effectiveness of the monoclonal antibodies mepolizumab and benralizumab in eosinophilic asthma.

Eosinophilic asthma is characterised by increased eosinophilic inflammation, recurrent exacerbations and poor disease control. The proportion of asthmatics with the eosinophilic phenotype varies with one study suggesting a prevalence of between 21% and 69% in adults. However, other work has suggested that while the prevalence is potentially less than 1%, asthma-related healthcare resource use among those with eosinophilic asthma was four times greater than for other phenotypes.

A further complication from eosinophilic asthma is that lung remodelling and airway hyperinflation leads to a persistent decrease in pulmonary function. Eosinophilic asthma is also associated with over-expression of Th2 inflammatory cytokines such as interleukin-5, which is known to play an important role in the recruitment and survival of eosinophils in peripheral tissues.

Two monoclonal antibodies approved for the treatment of severe eosinophilic asthma are mepolizumab and benralizumab. Mepolizumab binds to and inactivates interleukin-5 and in patients with severe asthma, requiring daily oral glucocorticoid therapy, mepolizumab has been shown to reduce disease exacerbations, improve symptom control and produce a steroid-sparing effect.

Similarly, benralizumab, which targets the interleukin-5 receptor alpha subunit, depleting eosinophils, has also been found to improve symptoms of severe asthma which remains uncontrolled by high-dosage inhaled corticosteroids and long-acting beta-agonists. While both monoclonal antibodies are effective, what remains unclear is whether there are any important clinical differences between the two agents.

This prompted a team from the Department of Respiratory Medicine, Hannover Medical School, Munich, Germany, to undertake a retrospective analysis of the comparative efficacy of the two monoclonal antibodies in severe asthma. Included patients were those with a physician diagnosed severe eosinophilic asthma, which despite the use of high-dose inhaled glucocorticoids and long-acting beta-agonists, plus optional second or third-line control, and/or oral glucocorticoids, did not provide sufficient control.

For such patients, the treating physician, decided to use either mepolizumab 100mg or benralizumab 30mg every four weeks for the first three doses and then once every eight weeks. The researchers focused on clinical factors such as asthma control, pulmonary function, exacerbation rates, oral glucocorticoid use over a 12-month period. Symptom data were collected at baseline and after 6 and 12 months.

A total of 187 patients, 123 given mepolizumab, were included in the analysis. The median age was 58 years (42% female) and 54% were described as non-smokers. Use of both monoclonal antibodies led to a significant improvement in pulmonary function as defined by changes in the forced expiratory volume in one second (FEV1). This increased from 59% to 74% for mepolizumab and from 63% to 72% for benralizumab.

The asthma control scores also significantly improved for both drugs: 13 to 19 (p < 0.001) for mepolizumab and 12 to 21 (p < 0.001) for benralizumab when assessed after 6 months. The number of exacerbations also reduced with 68% of patients in either group reporting no exacerbations at all during the 12-month follow-up period and there was a significant reduction in the dosage of oral glucocorticoids used.

The authors concluded that both monoclonal antibodies produced improvements in all clinically relevant measures and were considered to be equally effective. Furthermore, these improvements occurred after 6 months of therapy and were similar to the results obtained after 12 months.

Kayser MZ et al. Real-World Multicenter Experience with Mepolizumab and Benralizumab in the Treatment of Uncontrolled Severe Eosinophilic Asthma Over 12 Months. J Asthma Allergy 2021