Biology of Asthma and Biologics: A Primer

Aaron B. Holley, MD, FCCP

Disclosures

November 05, 2018

Editorial Collaboration

Medscape &

A Complex Disease

Asthma is a complex disease characterized by inflammation and airway abnormalities.[1] Multiple phenotypes, with varying underlying biology, are now recognized.[2,3] Although there are different paradigms for establishing relevant phenotypes, asthma can broadly be separated into two categories: eosinophilic (T-helper 2 [Th2]) and noneosinophilic (non-Th2).[4] Each category has a different underlying immunobiology, and recently approved medications for asthma all target the eosinophilic/Th2 type of disease.

For patients with eosinophilic/Th2 asthma, the disease is typically exacerbated by inhaled "triggers." Triggers include allergens, pollutants, and infections that make contact with the airway epithelium and induce an inflammatory cascade. This cascade includes multiple cytokines, or cellular messengers, that help coordinate an immune response to a given trigger. Cytokines, such as interleukins (ILs), interact with cells and immunoglobulins (Igs) to activate eosinophils, mast cells, and leukotrienes, and stimulate mucus and histamine release. The end result for the patient is bronchoconstriction; chest congestion; and cough, dyspnea, and wheezing.[4,5]

Recently developed monoclonal antibodies, also referred to as "biologics," target different levels of the eosinophilic/Th2 asthmatic response. Omalizumab blocks the interaction of IgE with its receptor and is approved by the US Food and Drug Administration (FDA) for the treatment of asthma. Mepolizumab and reslizumab are IL-5 antagonists and benralizumab is an IL-5 receptor antagonist—all are also FDA-approved for the treatment of asthma. Dupilumab acts on the IL-4 receptor and affects IL-4 and IL-13; recent studies[6,7,8] show benefit, and it is now approved by the FDA. As a group, this medication class has revolutionized asthma care and improved treatment options for patients with moderate to severe asthma.

Before discussing the pros and cons of each new biologic, several generalizations pertinent to this medication class must be made. First, no biologic is recommended as a first-line treatment for asthma. They should be considered for patients with eosinophilic/Th2 asthma who do not achieve disease control using oral and inhaler therapies (ie, those with moderate to severe asthma).[9] Second, all are expensive, and cost efficacy has not been definitively proven.[10] Finally, no trial has directly compared any one of these drugs with another, so choices between the drugs are largely based on patient biomarkers, cost, and ease of administration.[6,11] As one review[5] recently concluded, it is impossible to recommend one biologic over another as first-line therapy at this time.

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