Sometimes we are inclined to believe that history repeats itself, as highlighted by the famous remark by Santayana about not learning from the mistakes of the past. That cannot be said overall about the history of science —it is clearly an upward progression when the advances in DNA technology are considered. And, allergists have witnessed a relative explosion in options from that technology in the past 2-3 years.
From using ‘asthma cigarettes’ derived from the leaves of the thornapple plant in order to treat asthma in the early 1900s, through using inhaled steroids since the 1970s and using the ‘Singulair/Montelukast’ class of pharmaceuticals since the late 1990s, we are now in an era of using biologic treatment for certain types of asthma. ‘Biologic’ means that the treatment was created with the use of a living organism and that the treatment is directed against a specific molecule made by the immune system. A physician reviewer at an insurance company will typically look to see if other prescription medications for asthma have been tried before approving insurance coverage for a biologic treatment.
There are four biologic treatments that are currently FDA-approved for treating asthma. But, each one has been determined to be effective only when certain findings of the asthmatic patient are present. These four biologics (I’ll put the long scientific names in parentheses for those who are interested) are the following:
- Xolair (omalizumab) It was initially approved in 2003 for those 12 years of age and older who have year-round allergic asthma. But, the FDA gave approval in 2016 for its use in asthma starting at age 6. Xolair works by binding to the allergy antibody (IgE) that is in the blood and on the surface of certain immune cells. The asthma patient needs to have (a) a total allergy antibody (IgE) level between 30 and 700 IU/ml, (b) reactivity to a year-round allergen (which would be either a pet dander, dust mite or an indoor-predominant mold species) and (c) inadequate control despite using an inhaled corticosteroid. Xolair also has a FDA-approved indication for chronic hives of unexplained cause. The dose is given by injection into the arm either every 2 weeks or every 4 weeks, depending on the person’s total allergy antibody blood level and body weight.
- Nucala (mepolizumab). Approved in 2015, this is the first of the approved biologics that can affect one type of immune cell—called an eosinophil—that is too active in some patients with asthma. Nucala binds to a molecule that is a major stimulator of eosinophil production. The biologic is indicated for those 12 years of age and older with severe asthma and who have the presence of eosinophils in the blood. However, people without asthma can have eosinophils in the blood. The treatment is more likely to be effective if the blood eosinophil level is over 300, but some asthmatic patients could have improvement if the level is over 150. The dose should be prepared and given by injection into the arm every 4 weeks.
- Cinqair (reslizumab). Approved in 2016, this biologic binds to the same molecule to which Nucala binds in order to affect the eosinophil immune cell. Cinqair is only approved for asthmatic patients 18 years of age and older who have evidence of eosinophil production. Cinqair is more likely to work if the blood eosinophil level is greater than 400. Cinqair is given every 4 weeks through a vein (i.e. intravenously).
- Fasenra (benralizumab). Approved a few months ago, Fasenra also affects the eosinophil but does so by binding directly to the eosinophil. The biologic is indicated for those 12 years of age and older who have severe asthma and some presence of eosinophils. The dose is injected by a healthcare professional into the arm every 4 weeks for the first three doses, and then every 8 weeks afterward. Better results for reducing the number of bad episodes (i.e. exacerbations) and for increasing lung function are seen when the blood eosinophil level is over 300.
A fifth biologic called Dupixent (dupilimab)—already approved since early 2017 for treatment of atopic dermatitis in those 18 years of age and older—affects an entirely different molecule of the immune system and also shows promising results for certain asthma patients. Allergists are eagerly awaiting its approval, which may happen at the end of 2018, by the FDA for use in treatment of asthma.
When I have raised the topic of a 3- to 6-month trial of one of the first three approved biologics to those asthmatics who are not responding well to multiple classes of prescription medication, and to traditional ‘allergy shots’ if they have been on it, some patients have doubts about biologics. It is not a commonplace treatment that they hear about from family members, co-workers or friends. There is no history of frequent and highly visible advertisements in the media for biologics that treat asthma. They are not purchased easily, as inhalers and tablets are from pharmacies. The degree of cost coverage by an insurer is an obvious concern, which the pharmaceutical companies recognize and offset by offering programs that either reduce or eliminate the patient’s cost responsibility. Even though biologics are rigorously studied for safety and effectiveness in clinical trials, some patients are still skeptical that reported side effects could be underrecognized. Although a higher rate of a side effect in a clinical trial may not be statistically significant and may just be due to chance, we all have varying levels of tolerance for risk that need to be acknowledged.
Biologic treatment for asthma is not for every patient with asthma, and not necessarily for every asthmatic patient who has an allergic profile. Tests that are called biomarkers can help assess who is more likely to respond. These biomarkers include the level of exhaled nitric oxide along with the blood levels of eosinophils and the total allergy antibody level (IgE). The time, though, has arrived in the evolution of medicine for at least a careful consideration of using a biologic treatment—when the specifics of a person’s asthma control are not trending for the better over a considerable span of time, after using the typical prescription medications that can be dispensed at a pharmacy and when the status quo is just no longer acceptable to the patient.
Dr. Klein