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Common Biomarkers of Asthma to Determine Treatment Efficacy
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Stanley Goldstein, MD: Maybe now we could address the specific endotypes that may be a function of what these patients’ phenotypes are. We want to be thinking about those potential biologics and grouping these patients based upon what we would think would be best to help them in their uncontrolled asthma.
Giselle Mosnaim, MD, MS: If you look at endotypes, this is the way I look at it. There are different focuses, but one would be to focus on the pathways that the different biologics focus on. For example, the first biologic, omalizumab, focuses on binding free IgE.
Giselle Mosnaim, MD, MS: Another thing to focus on is eosinophil levels. We have reslizumab, we have mepolizumab, that focus on reducing eosinophil levels. And then we also have benralizumab that binds to the IL-5 receptor, and IL-5 promotes eosinophil maturation development. Then we have dupilumab, which binds to the IL-4 receptor alpha, and it inhibits IL-4 and IL-13 pathways in asthma. Depending on the different mechanisms, there are different biologics for those mechanisms. As Dr. Mustafa alluded to, while we don’t have them currently available, we are looking at biologics that would treat also Th2-low asthma. These are not approved yet, but it’s something that we’re looking at because the current biologics are focusing on Th2-high asthma, and we have many patients that are Th2-low asthma and we want to make sure to be able to offer therapies for them as well.
Stanley Goldstein, MD: Before we start getting into the specifics about the biologics, we know you’ve both been talking about T2-high and T2-low. What percentage of patients in the United States with uncontrolled asthma are T2-high versus T2-low, and what does that specific patient need? We know there’s a lot of variability in looking at the endotypes, about the biomarkers, and patients may have multiple biomarkers. How do you make that decision, to leap to decide which type of biologic they would benefit from? First, let’s address the T2-high and T2-low as far as how common they are among our patients.
Shahzad Mustafa, MD: The majority of asthmatics fall into a T2-high, an allergic or eosinophilic inflammation kind of picture. With that being said, when we’re getting into poorly controlled asthmatics, the ratio starts to skew a little bit over to T2-low. As Dr. Mosnaim said, we have less therapeutic options in that space, so they are a little bit more difficult to control for us. As an overall picture, it’s much more of an allergic asthmatic or eosinophilic asthmatic, but as we get into the poorly controlled ones, we see a skew going up towards a more T2-low picture.
Stanley Goldstein, MD: But we know that there are overlaps in the T2-high asthma patient population. There may be an overlap. We know that in the United States, 60% of patients, and as far as adults who have asthma have an underlying allergic cause or association. In children, that’s 80%. Four out of every five children who have asthma have an allergic cause for it. We have to try to piece together what is the driving force for that person’s asthma, and therefore try to decide what’s the appropriate biologic. At the same time, can we use any biomarkers that help us determine outcomes for asthma? If we’re going to put them on a biologic, are there any biomarkers that we could say, “Well, if this goes down or this goes up, this patient definitely is a sign that they’re going to be better”? Anything in that regard that can help us? Shahzad, you were smiling at that question. I’m sure you have some answers that you could …..
Shahzad Mustafa, MD: The more we know, the less we know.
Stanley Goldstein, MD: Absolutely true.
Shahzad Mustafa, MD: We have biomarkers that help us predict what we think a patient’s response will be. As eosinophil levels increase, we think their response to the anti-IL-5, the anti-eosinophil agents such as a reslizumab, mepolizumab, benralizumab, should get better. But, we are still not good in medicine about predicting the future and predicting outcomes. For omalizumab, we’re thinking about this in individuals with allergic asthma, with elevated IgE levels, but it is hard to predict their response. So I think that is an important part of us putting patients on these medications with our best guess, but our ability to predict a response remains suboptimal. But we do want to try to think through it like we have with phenotypes and endotypes to give us the best chance of success. And not only can we not potentially predict their response, we don’t necessarily change the course of their asthma. I think that’s an important point. We try to help symptoms, we try to decrease exacerbations, and these are very effective, well-tolerated mediations that we’re going to get into, but we don’t actually change the course of their asthma. That’s an important point that we all have to appreciate.
Stanley Goldstein, MD: Giselle, anything to add to that discussion?
Giselle Mosnaim, MD, MS: What I would like to add is a little bit different. You had mentioned earlier the difference between difficult-to-control asthma and severe asthma. Ycan have someone with severe asthma that is well controlled, so they have severe disease, but they take their medications, they avoid triggers, all of these things so they can be well controlled. And you can have someone that doesn’t have as severe disease, but they can be quite uncontrolled and require repeat courses of oral steroids, emergency department visits, and hospitalizations. It’s very difficult to really disentangle all of this.
Transcript Edited for Clarity
