Reply to Lipworth et al.: Don’t Forget about Facilitatory Effects of Corticosteroids on β₂-Adrenoceptors in Acute Asthma

From the Authors:

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that depletion of circulating eosinophils is the only effect OCS are likely to have that are not shared with ICS (3).

Because OCS are known to have severe side effects, and in noneosinophilic exacerbations of chronic obstructive pulmonary disease they are actually harmful (4), it would be a significant advance to determine whether a combination of ICS and rapidly acting anti–IL-5 treatment would cover all the benefits of OCS in acute asthma while mitigating the harms of OCS. With respect to this, we recently published a case report (5) that showed the addition of benralizumab to ICS resulted in a dramatic improvement of peak flow and FEV₁ within 6 hours when given to treat an asthma attack in a patient in whom systemic corticosteroids were contraindicated. We believe that these findings support the idea that systemic targets of benralizumab that express the IL-5 receptor (such as eosinophils and basophils) play a pivotal role in sustaining the nonbronchodilator responsive airflow limitation seen in asthma attacks.

The use of benralizumab in acute asthma may also provide other benefits. Treatment failure is a major issue in the current acute asthma treatment paradigm (6). The longer half-life of benralizumab and the harms of systemic corticosteroids may tip the cost–benefit assessment in favor of benralizumab.

We agree that more work is needed before benralizumab becomes an option for the management of asthma attacks. Nevertheless, the rapidity of eosinophil depletion certainly makes it an exciting prospect. We look forward to the results of our clinical trial to examine this idea (clinicaltrials.gov ID: NCT04098718).