What to Consider When Prescribing Biologics in Severe Refractory Type 2 Asthma

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Researchers evaluated the use of a pragmatic algorithm for identification of the optimal biologic class to treat patients with specific type 2 asthma endotypes.

Use of a pragmatic algorithm to identify of optimal biologic class for the treatment of patients with specific type 2 (T2) asthma e endotypes was evaluated in a clinical perspective published in The Journal of Allergy and Clinical Immunology: In Practice.

The selection of the optimal biologic agent for the treatment of patients with severe refractory T2 asthma presents a challenge, with the evidence strongly in support of endotype-driven prescribing of biologics in this population to attain clinically relevant outcomes. Therefore, investigators sought to provide a focused pragmatic, real-life guide for physicians based on currently available guidance on biologic treatments, with particular reference to common T2 endotypes, rather than an extensive systematic review.

In patients with T2 asthma, the use of monoclonal antibodies that target immunoglobulin E (IgE), interleukin 4 receptor alpha (IL-4rα), and interleukin 5 (IL-5) are all considered to be attractive treatment options, having been shown to decrease exacerbation rate and oral corticosteroid dose requirement, as well as to improve patients’ quality of life, pulmonary function, and symptom control. The need exists to determine which biologic agent is best suited to a patient with asthma, based on their particular disease endotype.

In clinical practice, fractional exhaled nitric oxide (FeNO), peripheral blood eosinophils (PBEs), and allergic status are the most commonly used T2 biomarkers for the assessment of asthma in clinical practice. Patients with T2 asthma who have eosinophilic endotypes appear to do well when treated with anti-IL-5rα agents, which include mepolizumab, benralizumab, and reslizumab, with these medications having been shown to decrease exacerbations in patients with severe eosinophilic asthma by approximately 50%.

Additionally, in patients with severe, uncontrolled allergic asthma, the anti-IgE biologic omalizumab is effective, having been shown to be associated with a 25% decrease in the occurrence of exacerbations of asthma. Further, in patients with FeNO-high endotypes, the use of such anti-IL4rα agents as dupilumab is considered effective, having demonstrated a 47% reduction in exacerbations of asthma.

Before prescribing biologic therapy, clinicians should consider the presence of comorbidities in patients with T2 asthma, including chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, idiopathic urticaria, and atopic dermatitis.

The investigators concluded that additional head-to-head studies in patients with severe refractory T2 asthma are warranted to compare biologic agents in patients with mixed endotypes, based on their FeNO levels, PBEs, and allergic status.

The selection of a biologic agent can ultimately be determined by carefully considering a patient’s particular endotype, comorbidities, and existing clinical data, along with relative cost of the agent, dosing interval, and the availability of self-injection.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Chan R, Kuo CR, Lipworth B. Pragmatic clinical perspective on biologics for severe refractory type 2 asthma [published online July 12, 2020]. J Allergy Clin Immunol Pract. doi:10.1016/j.jaip.2020.06.048