Response Biomarkers to Determine Efficiency in Treating Asthma

Transcript:Geoffrey L. Chupp, MD: The other thing I’ll just add that I didn’t mention in terms of looking for comorbidities—I’m sure this group does this a lot as well—is we look hard for evidence of immunodeficiency in these individuals and chronic infections. Sometimes we find IgE [immunoglobulin E] deficiency, and they may require bronchoscopy to look for infectious organisms that might not otherwise be picked up, because they don't cough up a lot of sputum, and you can’t get a sample. High-res CT [computed tomography] is very important as well here, because if you demonstrate that there’s bronchiectasis, then you know you’re probably not dealing with a classic asthmatic-type phenomenon.

Michael E. Wechsler, MD, MMSc: One thing that we can all agree on is that while we’re happy to have the biomarkers we have, I think there’s a huge unmet need for other biomarkers that can help guide us and pinpoint the specific type of asthma and guide us to the right kind of therapy. In particular for non—type 2 disease, we don’t really have any biomarkers. Some people suggest maybe neutrophils in the sputum might be effective, and people are doing work and looking at IL-6 levels and C-reactive protein as a surrogate of that, but we don’t really have any good non–type 2 biomarkers, and we need better predictive and better response biomarkers for our patients.

When I say response biomarkers, what I mean is we know, for instance, that when you give an anti—IL-5 therapy, the eosinophils are going to go down. That doesn't necessarily correlate with clinical responsiveness in all people.

Stanley Goldstein, MD: I think that’s a very important point that Mike is saying. We have no biomarkers that we can measure as far as outcomes. Even when we’re looking at eosinophils, obviously it’s IL-5, but the decrease in the eosinophils absolutely does not correlate with clinical outcomes. When you’re looking at total specific IgE, it’s the same thing. I mean, you can look at total IgE and measure it. It probably does go down. Obviously, you cannot use commercial labs for it. Also, there’s no correlation. If we had better correlation, I think we’d understand better how to use the existing biomarkers.

We need other biomarkers where we’re missing the boat, so to speak, and there’s a major overlap. That's the other important issue, with respect to biomarkers that we measure, what we do, and we know—in my own world, I have patients who I think would benefit from an anti—IL-5 decreasing their eosinophils to zero, and nothing changes. I have a couple of patients who are on 2 anti-inflammatory medications, like an anti–IL-5 and anti-allergic at the same time.

Michael E. Wechsler, MD, MMSc: I think that bespeaks the complexity of asthma and that there can be many different types of asthma that go on at different times. Sometimes, you might have more of an eosinophilic-mediated asthma, and the same individual can have a non—type 2 mediated asthma at a different time. Even if you block the type 2, then you might still have some non–type 2 inflammation, or you might have some other component of the type 2 inflammation that’s active. All these concepts are important. They point to the heterogeneity of asthma and the heterogeneity of response.

Transcript Edited for Clarity