COMMENTARY

Biologic Agents Are Changing the Landscape of Severe Asthma

Nicholas J. Gross, MD, PhD

Disclosures

August 17, 2018

While corticosteroids are effective in most patients with severe asthma, 10%-20% of patients with severe or very severe asthma continue to have acute exacerbations despite optimal doses of corticosteroids. Decades ago, it was recognized that some patients with steroid-resistant asthma had elevated blood eosinophil levels. In addition, eosinophilia was associated with elevated cytokines, specifically interleukin (IL)-4 or IL-5. With the advent of biological therapeutics, it has become possible to address eosinophilia in those "steroid-resistant" patients with asthma with the administration of IL-4 or IL-5 antagonists or receptor antagonists. We now have three such agents that are approved for asthma by the US Food and Drug Administration (FDA): mepolizumab, reslizumab, and benralizumab. Dupilumab is currently under review by the FDA. The relative efficacy of these agents will not be known until head-to-head clinical trials are performed, but at present, they are generally considered equally effective.[1]

In which patients would administration of one of the above agents be appropriate? Authoritative reports suggest that patients with severe or very severe asthma and who have blood eosinophil counts of ≥ 300 cells/μL should be considered.[2] In general, the higher the eosinophil count, the greater the response to an anti-eosinophil agent. Other markers for appropriate administration of a biologic remain to be discovered and validated.

What effects can be expected when a biologic has been administered? Available data suggest that lung function, typically the FEV1, should increase by at least 100 mL or more. Symptoms should improve, and acute exacerbations should decrease in frequency and severity. The need for corticosteroids decreased by at least 50%, according to one study of dupilumab.[3]

It is also appropriate to consider the costs of long-term treatment with a biologic as well as the inconvenience of long-term administration.

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