Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published January 12, 2022


Have biologic agents for severe asthma been compared to each other in head-to head trials?

Type 2 inflammation in asthma is generally suppressed by glucocorticoids. However, in a subgroup of patients with severe asthma, airway eosinophilia persists despite the use of high-dose inhaled glucocorticoids or oral glucocorticoids. Read the NEJM Review Article here.

Clinical Pearls

Q: What are the characteristics of type 2 high-inflammation asthma?

A: Severe asthma is heterogeneous biologically, with distinct patterns of airway inflammation defined by the predominant granulocyte in sputum or bronchial biopsy specimens and often identified by means of blood or exhaled-breath biomarkers. Type 2 high-inflammation asthma is characterized by eosinophilic airway inflammation, which is associated with increased blood eosinophil counts or elevations of fractional exhaled nitric oxide (Feno), whereas type 2 low-inflammation asthma encompasses neutrophilic asthma and paucigranulocytic asthma.

Q: What type 2 cytokines provide therapeutic targets for biologic agents to treat severe asthma?

A: Type 2 cytokines include interleukin-5, interleukin-4, and interleukin-13. Interleukin-5 promotes proliferation, differentiation, activation, and survival of eosinophils. The numbers of eosinophils in peripheral blood, bronchoalveolar lavage fluid, and bronchial biopsy specimens directly correlate with the severity of asthma. Interleukin-4 and interleukin-13, which share interleukin-4 receptor α, have many overlapping functions. Interleukin-4 plays a key role in CD4+ type 2 helper T lymphocyte differentiation and drives IgE isotype switching in B lymphocytes. Interleukin-13 induces the contraction of airway smooth-muscle cells and stimulates inducible nitric oxide synthase in bronchial epithelial cells, which leads to an increase in Feno.

Morning Report Questions

Q: What are some of the biologic agents that allow reductions in glucocorticoid dose for patients with glucocorticoid-dependent severe asthma?

A: In clinical trials, several anticytokine antibodies enabled tapering of oral glucocorticoids with the use of predefined schedules while asthma control was maintained in adults with glucocorticoid-dependent severe asthma. Mepolizumab (100 mg administered subcutaneously every 4 weeks) reduced the glucocorticoid dose by a median of 50%, as compared with placebo, while reducing the annualized rate of exacerbations by 32% and improving asthma control, findings that were supported by real-life observational studies. Benralizumab (30 mg administered subcutaneously every 4 or 8 weeks) significantly reduced the median oral glucocorticoid dose from baseline to 28 weeks, as compared with placebo (a 75% reduction vs. a 25% reduction). In contrast, neither fixed-dose subcutaneous reslizumab (110 mg every 4 weeks) nor fixed-dose subcutaneous tezepelumab (210 mg every 4 weeks) reduced the daily oral glucocorticoid dose in patients with glucocorticoid-dependent severe asthma.

Q: Have biologic agents for severe asthma been compared to each other in head-to head trials?

A: Since no data from head-to-head randomized controlled trials comparing the efficacy, real-life effectiveness, and long-term safety of monoclonal antibodies in patients with severe asthma are available, high-level evidence is lacking to guide clinical decision making. Criteria such as dosing frequency, route of administration (subcutaneous or intravenous), whether drug administration requires monitoring by health care personnel, age at onset of asthma, biomarkers, coexisting conditions (e.g., atopic dermatitis and nasal polyposis), insurance coverage, cost, and patient preference are taken into account in choosing an available therapy. In patients with oral glucocorticoid–dependent severe asthma, the percentage reduction in the glucocorticoid dose with maintenance of asthma control is a critical outcome measure.

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