Targeting the eosinophil key in severe allergic asthma, studies suggest

The clinical response to anti-IL5/5R drugs mepolizumab and benralizumab appears to be the same in patients whether or not they have a severe allergic component to their asthma, research suggests.

A team at Guy’s Severe Asthma Centre in London compared clinical outcomes with the monoclonal antibodies between patients who were also eligible for omalizumab because of severe allergic asthma and those who were not.

Across a range of measures, the retrospective analysis of 228 patients who had been started on mepolizumab and benralizumab between 2017 and 2019 showed no difference in clinical outcome according to eligibility for omalizumab.

In all 48.5% of patients met the criteria for omalizumab when they started the anti-IL5 treatment, but there was no difference in exacerbation rate reduction and similar improvements in both asthma control and lung function, the team reported in the European Respiratory Journal.

Other key measures such as reduction in maintenance oral corticosteroid dose also showed no differences between the groups.

It follows a study from the team published in January which showed that the clinical effectiveness of mepolizumab and benralizumab is independent of baseline fractional exhaled nitric oxide. Even patients with the highest FeNO levels have excellent responses to anti-IL5/5R therapies, they concluded.

Study author Dr David Jackson, consultant respiratory physician at Guy’s and St Thomas’ NHS Trust, said there has never been a prospective randomised head-to-head study of the available biologics, but this real-world data shows that patients with severe allergic asthma who meet all the criteria for omalizumab do very well when you target the eosinophil.

“Patients with severe allergic asthma do just as well with an anti-eosinophil approach as patients who have no allergy at all driving their eosinophilic inflammation,” he told the limbic. “The results question who, if anyone, should be offered omalizumab first-line, and  highlights the central role the eosinophil plays in severe asthma.”

Biologic choice increasingly comes down to whether other comorbidities are present that would benefit from your choice, he explained.

“In the absence of head-to-head studies, certain comorbidities can drive the decision. For example, if the patient has severe eczema, dupilumab would be first-choice. If the patient suffers with severe urticaria then omalizumab would be a good option.”

Both the studies build on the idea that often our preconceptions are wrong, he added.

“We’ve seen many patients who were started on omalizumab because they are allergic,but then continue to exacerbate or are unable to wean off their prednisolone,” Dr Jackson said. “These real-world data show that targeting the eosinophil is effective regardless of what the IgE or FeNO levels are.”

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