Biomarkers in Shifting the Treatment Paradigm of Asthma - Episode 4

Role of Biomarkers in Allergic Asthma

May 19, 2020

Transcript: Thomas Casale, MD: Mike, what about biomarkers? Do you use them to test for asthma or a phenotype of asthma, especially point-of-care biomarkers?

Michael E. Wechsler, MD, MMSc: I think it’s critical to try to identify what type of asthma an individual has. I think for every patient with asthma, we should be doing that, even from the onset, whether they have severe disease or whether they’ve got milder disease. I think we want to know what type of asthma the individual has so that in the event that they become poorly controlled on standard-of-care therapies, inhaled corticosteroids and long-acting beta agonists, we can then have a plan about which direction we’re going to want to go in.

So, there aren’t that many kinds of biomarkers that we do have. The ones that we have are somewhat effective in terms of defining type-2 [T2] or non—type-2 asthma. For type-2 asthma, we have eosinophils, which can be identified in the blood or in the sputum. They reflect activity of interleukin [IL] 5. We also have exhaled nitric oxide, which can be done as a point-of-care test. It’s a rapidly available, easily procured technology to identify interleukin 13–mediated inflammation. That’s something that you could do on the spot. The eosinophils in the blood, at least, are quite readily available, as well. The third kind of biomarker that we have available to us for identification of the types of asthma is really to identify allergic asthma. We can look at IgE [immunoglobulin E] levels, and certainly, we can also use skin testing and specific IgEs to different aeroallergens. That can reflect allergic inflammation, allergic asthma, as well.

By using a combination of these biomarkers, you can identify whether there’s a greater propensity to respond to some of the biologics we have, whether it’s anti—IL-5, anti-IgE, or the anti-IL-4/13 therapies. I think that these should be widely used. They should be used early on, and they can be used later on. One can also follow these biomarkers.

The biomarker with we have need to identify whether they’re good predictive biomarkers or response biomarkers. The eosinophil is an excellent predictive biomarker for responsiveness to anti—IL-5, as well as to anti-IgE therapy, to some extent, and as well as to anti–IL-4/13 therapy. IgE tells you that you have asthma but doesn’t necessarily predict responsiveness to anti-IgE. You can have a low IgE level and respond to anti-IgE. You can have a high IgE level and not respond to anti-IgE. So, it’s important to recognize these biomarkers with where they play.

Thomas Casale, MD: Either you or Stan, do you have sort of cutoff levels that you use for these biomarkers, like eosinophils or pheno?

Stanley Goldstein, MD: Let me partially echo what Mike has said and just relate the way I use biomarkers and the levels of biomarkers. We’ve been trying to compartmentalize everything and say, OK, if the eosinophilic asthma, allergic asthma, whether it’s pheno—as far as a biomarker, there’s major overlap in all these biomarkers. We’ve been talking about T2-high asthma, which is the most common asthma phenotype in the world, probably in the United States, for sure. We know that 70% of patients who have asthma have a T2-high asthma.

But, within that T2-high asthma, you can have elevated eosinophils. You could have specific IgE, with elevated total IgE. You could have elevated pheno. So, it’s hard to just put them in compartments, because it sort of says “This is the way you have to treat it”. You look at patients who have elevated eosinophils—and there was a study that looked at this—as far as the degree of T2-high asthma, and you find that with those patients who have elevated eosinophils, as the numbers of eosinophils go up there’s a greater overlap with, so to speak, allergic asthma. When do you treat it as allergic asthma with an antiallergic drug or when do you treat it with an anti—IL-5 drug? It’s still difficult to say.

We know that patients can—we may think that they have allergic asthma. We’ll treat them for allergic asthma, say, with omalizumab, but they don’t respond. Then we may use an anti—IL-5, so there’s a lot of overlap, and there’s a lot we don’t know. I think that is an inherent problem in the way we are sort of breaking it down.

Thomas Casale, MD: I think that’s one of our biggest problems. We don’t have very specific biomarkers for each of the drugs that we want to employ. If you have eosinophils, as Mike alluded to, every biologic appears to work better. If you have high pheno, perhaps that would persuade you to consider something that would block IL-13, like dupilumab. There is a lot of overlap, and I think that’s one of the biggest problems, along with 1 other issue we find, and that is the T2-low asthma patients.

Transcript Edited for Clarity