Sample: What are the 3 most common biomarkers used when considering which biologic medication to use in severe asthma?
With severe asthma affecting between 5% to 10% of adults with asthma, how much do you know about the diagnosis of severe asthma and the different treatment options for patients? Answer the 5 tricky questions below to find out.
Question 1. Which of the following patients has severe asthma?
A. 32-year-old woman with daily symptoms of wheeze and night cough; inspiratory and expiratory wheeze on examination; uses albuterol and montelukast as directed
B. 78-year-old man with chronic cough, frothy sputum, increasing dyspnea on exertion, and lower extremity edema
C. 21-year-old woman who just moved to town; uses dual inhaler of high-dose inhaled corticosteroid (ICS) with long-acting beta agonist (LABA) as directed, but still has expiratory wheezing on examination and wakes up coughing twice weekly
Answer: C. Patient C is experiencing uncontrolled asthma symptoms despite using a high-dose ICS/LABA combination as directed. Severe asthma is defined as asthma that requires treatment with high-dose ICS plus a second controller, but remains “uncontrolled” despite this therapy. Patient A has undertreated asthma since she is only taking a short acting bronchodilator and an oral leukotriene inhibitor. Patient B likely does not have asthma, but needs a workup for congestive heart failure. The clue is the frothy sputum and peripheral edema.1
Question 2. When referring to asthma, the term biologic therapy suggests:
A. Modifying patient environment so inherent biologic processes may return to normal, thus improving asthma without the use of additional medication
B. The biological benefit of weight loss and exercise that naturally enhances the pulmonary system’s ability to perform
C. Use of novel therapies that target specific pathways in asthma
D. There are no biologic therapies for asthma
Answer: C. Biologic therapy for asthma is based on blocking specific downstream pathways. Answer A refers to avoiding asthma triggers by managing one’s surroundings, which is a fundamental concept in the holistic approach to asthma, but is not referred to as biologic. Answer B mentions exercise, which is also part of a comprehensive asthma treatment plan, however, this is not biologic therapy.
Question 3. Which pathway is NOT a target of biologic therapy in severe asthma?
A. Immunoglobulin E (IgE)
B. Interleukin (IL) 6
Answer: B. IL6 antagonism is used in the treatment of rheumatoid arthritis. All of the other pathways are fundamental in the treatment of severe asthma. Omalizumab binds to IgE thus inhibiting activation of mast cells and basophils. Benralizumab, mepolizumab, and reslizumab antagonize IL5; dupilumab antagonizes IL4 and IL13.
Question 4. What are the 3 most common biomarkers used when considering which biologic medication to use in severe asthma?
A. IgE, blood eosinophil count, fractional exhaled nitric oxide (FeNO)
B. IgE, fibrinogen, blood eosinophil count
C. Blood eosinophil count, mast cell degranulation assay, FeNO
D. IgE, blood eosinophil count, serum periostin
Answer: A. IgE, blood eosinophil count, and FeNO are the 3 key biomarkers to help guide clinicians in the selection of a biologic agent for the treatment of severe asthma. Fibrinogen is used as a weak biomarker for COPD progression. Mast cell degranulation assays are not commonly used in clinical practice. Serum periostin measurement as a biomarker for IL13 antagonists failed to meet investigational outcome goals and is no longer considered for use as an asthma biomarker.2
Question 5. The primary outcome in studies in severe asthma and the use of biologic therapies is:
A. Decreased exacerbations
B. Decreased mortality
C. Improved exercise performance
D. Decreased IgE and eosinophil counts
Answer: A. Decreased exacerbations was the primary outcome of Phase III clinical trials for omalizumab, all IL5 antagonists, and dupilumab, the IL4 and IL13 dual antagonist. Dupilumab also showed improvement in lung function. No clinical trial studying biologic asthma treatment measured a significant decrease in mortality. Exercise performance was not routinely measured in clinical trials for biologic agents. IgE level and eosinophils counts were not primary endpoints.3
1. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation, and treatment of severe asthma. Eur Respir J. 2014;43:343-373.
2. Manka LA, Wechsler ME. Selecting the right biologic for your patients with severe asthma. Ann Allergy Asthma Immunol. 2018;121:406-413.
3. Rabe KF, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid dependent severe asthma. N Engl J Med. 2018;378:2475-2485.