Pediatric Pulmonologist Mandeep Jassal on Biologic Treatments for Children with Severe Asthma

Mandeep S. Jassal is the primary pulmonologist in the Pediatric Asthma Clinic at Johns Hopkins Children’s Center. Here he discusses the clinic’s approach in treating children with severe asthma, including the use of novel biologics.

When is asthma considered severe?
For us, asthma is deemed severe when the patient does not respond to the standard therapy of systemic corticosteroids or high-dose inhaled corticosteroids and long-acting beta-agonists. Severe asthma affects about five percent of all asthmatic patients, though these children may experience life-threatening acute attacks along with the side effects of high-dose oral corticosteroid treatment. The disorder may dramatically impact the child’s quality of life, due to absence from school.

How do you determine whether a child has severe asthma?
The diagnosis is usually based on the physician’s evaluating the patient’s respiratory symptoms and response to asthma-directed therapies. Once that’s been established, that’s your diagnosis. The other way severe asthma can be established is through lung function testing, which we do in our clinic. Both are reasonable strategies for diagnostic and clinical judgment.

That’s it?
In our clinic, we take it one step further. Not only do we do lung function testing to better understand if the child has asthma and to get a better history of that asthma, but we also classify or characterize the asthma in greater depth in the lab to determine the child’s asthma phenotype. This is what we do during the first visit to understand the type of asthma, the type of severe asthma, and whether the child would qualify for asthma biologic therapy at that point. Not all patients will respond or qualify for asthma biologic therapies.

What are biologic therapies, and how do they work?
Biologic medications, which are produced from living organisms, include allergenics, blood components, gene therapy, recombinant therapeutic proteins, tissues and vaccines. Asthma is driven by an immune mechanism through different pathways, and asthma biologics work by blocking certain parts of that allergic or eosinophilic pathway to reduce the inflammation that derives asthma. If you have those two general categories, you would be a good candidate for biologic therapy.

Which biologics have been approved for children?
There are two biologics for children ages 6 years and up. One is omalizumab, or Xolair. Another treatment approved for 6-year-olds and up is mepolizumab, or Nucala. Among the drugs approved for children ages 12 years and up are benralizumab, or Fasenra, and dupilumab, or Dupixent.

How effective are they?
They’re pretty good. Most can reduce steroid-induced exacerbations by 50 percent, so you will definitely see a reduction in exacerbations. Patients report improved asthma control and quality of life. So, there are definitely great benefits with these therapies. You can appreciate it usually within the first couple of months of therapy.

Do some patients respond better to certain biologics?
That’s still a matter for research pursuits, but, in general, patients do respond as a whole to the therapies. A small percentage of patients need to be switched to a different therapy or stopped because of side-effect concerns. Switching therapies can be beneficial, and that’s why we keep a close watch on patients, seeing them about every three months. That’s when we can have a conversation after an appropriate observation period of discussing the need for switching therapy.

Are biologics safe for children?
Each biologic has a different side effect profile, which we review with the patient family. We don’t rush and tell the families which drug we’re going to use. We often have two biologic agents that may work well for the child, so we review the side effect profiles and administration of each medication and jointly make the choice with input from the patient and family. It’s done in a collaborative way. It’s a big decision to get an injection — whether in the clinic setting or the home.

What is the frequency of injections?
Some biologics are injected every two weeks, every four weeks, and others at an even longer frequency. There are different formulations and administration patterns, so it helps to know what the family prefers.

How have families responded?
Reasonably well, I think. The reason is our approach. Right from the start, we talk about the laboratory workup and the possible use of biologics, if the child has moderate to severe, and definitely severe, asthma. We don’t hesitate with these conversations; we don’t wait until things get worse. I’ve found that initiating conversations earlier results in a better provider-patient relationship going forward.

How would you distinguish our severe asthma clinic?
One thing that makes us stand out in asthma care is what we offer in the lung function category. We have the ability to do comprehensive lung function tests — not only in spirometry or lung volumes or diffusion testing, but now in a type of lung function testing called FOT, or forced oscillation technique. This is a noninvasive method that allows us to evaluate the lungs of very young children or those sensitive to airway obstruction.

What are some other noteworthy features of the clinic and lab?
We get a lot of referrals for exercise-induced shortness of breath and asthma, which is a pretty common reason for referral. We’ve created different protocols to understand the basis of each patient’s shortness of breath. Is it indeed asthma, the heart or another lung disorder, or is it something in the upper airway, such as vocal cord issues? In all of these ways we consider our clinic a unique referral source.