Thomas B. Casale, MD: Choosing an Asthma Biologic

November 9, 2019
Kevin Kunzmann

Clinicians now have 5 agents to select from—but a limited variation of action, and an even more concise patient population eligible for treatment.

Clinicians now have 5 biologics at their disposal for the treatment of asthma. But a growing pool of therapies does not make a selection for individualized care any easier.

In an interview with MD Magazine® while at the American College of Allergy, Asthma & Immunology (ACAAI) 2019 Scientific Meeting in Houston, Thomas B. Casale, MD, professor of medicine at USF Health Morsani College of Medicine, detailed how the matter of selecting a single biologic for an actually eligible patient with asthma has not been eased by more options.

MD Mag: What is the understood role of biologics in asthma treatment?

Casale: You know, we have 5 biologics approved for asthma. There’s several more in development. We feel like only about 5 or 10% percent of patients with asthma are appropriate candidates for biologics—that if we do a better job in educating patients about avoiding triggers, appropriate use of inhalers—and you think that's relatively simple but it's not. We see a lot of patients that don't know how to use their inhalers and they don't use them on a schedule that we recommend.

So obviously, before we even consider a biologic, we want to make sure that all of those bases are covered and then what biologic, and who's going to respond. That's been a big issue. So the 5 biologics we have, they all work on what we call this type 2, high inflammation manifested by either an allergic or an eosinophilic type of phenotype.

And we struggle to try and define not only who's an appropriate candidate, but which of the 5 do I pick, because a lot of the biologic mechanisms that they attack, there's overlap. So the 3 broad categories—we have a biologic that attacks IgE, the major antibody that makes you allergic; we have biologics that attack IL-5, which is important for eosinophil growth and differentiation; and then we have another biologic that attacks IL-4 and IL-13, which is important for switching B cells from making IgM to IgE, and also promoting this overall allergic and eosinophilic inflammation.

All of them work better in patients that have high blood eosinophils. So as a biomarker, it's helpful for me as a clinician to say if you have high blood eosinophils, you'll probably respond better to these drugs. It doesn't help me as much to discriminate which one to pick ,and that's a big part of the discussion.

Some of it depends upon what you're trying to achieve. Some are better at improving FEV1 or lung functions than others. Some, there are a little bit more specific biomarkers—so dupilumab, which is the IL-4 and IL-13 blocker, clearly works better in patients that have both high blood eosinophils and high exhaled nitric oxide, which most primary care physicians aren't going to measure. And even specialists don't measure exhaled nitric oxide much.

But we are encouraging everybody to measure blood eosinophils, because if they're up, we know that these patients will respond better to biologics. But they also respond better to inhaled corticosteroids. If you don't have that type of Th2-driven inflammation, you're probably not going to respond very well to inhaled corticosteroids either.

So that's a whole group of patients that I think we have problems with in appropriately diagnosing, and then getting good therapies for.