Precision Medicine in the Treatment of Severe Asthma - Episode 13
This is part of the MD Magazine® Peer Exchange, “Precision Medicine in the Treatment of Severe Asthma.”Click here for Segment 14 and learn about evaluating response to biologic therapy in asthma.
Peter Salgo, MD: We have these 4 new drugs, if you will. What do you take into consideration when you’re trying to decide which of these drugs to prescribe? Are there phenotypes that you know are going to have a better response? What are their biomarkers? How do you do that?
Raffi Tachdjian, MD: Again, we don’t have the science down precisely yet to determine whose phenotype or, as I said, endotype will be best fitted for that type of therapy. And so we go by the biomarkers—our fractional exhaled nitric oxide (FeNO), or eosinophils, sputum eosinophil, IgE [immunoglobulin E] count. Still, it may be a bit of trial and error as we settle into what fits best for that particular patient, for that particular time.
Neal Jain, MD: I would say that we’re a little bit behind oncologists with these therapies. They have an idea of “This is the genotype that we’re looking at. These are the genetic differences that exist, and we can target therapies according to that.” I think that’s coming. There’s some exciting research that’s being done by a variety of individuals at a variety of institutions, in looking at genomics and different proteomics and all these different things. But right now, what we have are these somewhat dirty biomarkers like exhaled nitric oxide, IgE, and eosinophils. IgE, in general, is a marker of T2 inflammation. Other than that, it can’t be used. It says “Oh, this pathway is somewhat turned on.” But other than that, it isn’t predictive of responsiveness.
Peter Salgo, MD: You’re not being helpful here.
Neal Jain, MD: I know. I would say that there are some data.
David Rosenstreich, MD: Well, biology is not helping us out here.
Neal Jain, MD: Right. And our understanding, right? There are some data that do suggest that if you have this higher eosinophil count, higher exacerbation rate, and higher exhaled nitric oxide, the likelihood that you’re going to respond to these therapies is better. But does 1 biomarker predict which of these therapies is going to be beneficial? That is where we’re lacking in data.
Peter Salgo, MD: That’s where I was going.
David Rosenstreich, MD: For the ones that we have now, for the IL-5 inhibitors, the eosinophilia appears to be the best biomarker for who’s going to respond to those 3 drugs.
Neal Jain, MD: And exacerbation rate.
David Rosenstreich, MD: Right.
Peter Salgo, MD: What about Xolair? How do you decide on that?
Neal Jain, MD: Right. There’s one published study, that’s decent, that suggested that FeNO was better than periostin, was better than eosinophils, in identifying patients who were more likely to respond. It didn’t say that if you had a low FeNO, you wouldn’t respond—you’re just less likely to respond.
Peter Salgo, MD: This is tricky stuff, right? Is it reasonable to ask a primary care doctor to make this kind of choice?
Raffi Tachdjian, MD: Well, already, as specialists, we’re having a hard time.
Peter Salgo, MD: Is that a no? Am I hearing no?
Raffi Tachdjian, MD: It is a no, but it’s a work in progress. Neal alluded to the oncologists. When you look at tumor markers, it’s not a dynamic process. Your therapy is quite precise and you’re just chasing this thing out. Here we’ve got multiple mechanisms at play and interplay. It’s tough to try to decide between 2 therapies that are quite targeted for the same patient. A frequent question that I get asked by primary care doctors is “Which product do you choose if both biomarkers are elevated?”
Peter Salgo, MD: OK.
David Rosenstreich, MD: Right now, given our level of understanding, specialists probably have to prescribe these. Somewhere down the road, when people are comfortable with them and we have a better idea, maybe anyone can prescribe them. But right now, trying to select among all of them requires knowing a lot and having a lot of data and experience.
Peter Salgo, MD: Other than the mechanism at the molecular level, are there patient-driven decisions? One of them, as you said, was intravenous. The others are parenteral. Are they all parenteral?
David Rosenstreich, MD: Everything else is subcutaneous.
Peter Salgo, MD: All of them?
David Rosenstreich, MD: Right. And one is intravenous.
Peter Salgo, MD: Does that make a difference? How often do you have to re-dose? How often do you bring them back? Are there differences here that you need to consider?
Neal Jain, MD: Absolutely. I think there are a variety of factors that play into that. Ultimately, there may be some that will be on the market soon that will be administered at home. Is that a good thing or a bad thing? Are patients going to be adherent if they’re self-administering and are feeling good? Some of them are once-a-month therapies, for a few months. And then they are administered every other month. And some of them are intravenous. Patients have to go to an infusion center or a specialized center that can administer them. Those are factors that you have to discuss with your patients when you’re trying to decide on therapy.
Peter Salgo, MD: But, again, every one of these drugs involves a needle—whether it’s an intravenous or subcutaneous option. In the diabetic community, there’s been resistance, which has been breaking down pretty rapidly now, to using these drugs (like insulins) that you need to inject. How do you deal with a patient who says, “Look, I’ve got my inhaler. I’m taking my pills. I’m doing all right. I don’t want a needle.”? What do you do?
Neal Jain, MD: Fortunately, the population that we’re talking about (patients who are exacerbation prone and are severe) get to a mind-set where they want something more. They are certainly open to the idea of something that is going to help them, that will hopefully help reduce their need for medications—oral corticosteroids, for sure, and sometimes some of the other medications that they’re taking that are quite costly and cumbersome to take. So something they’re doing subcutaneously, or in the office once a month or every other month, is palatable to them.
David Rosenstreich, MD: As allergists, we’re giving people shots all the time. A lot of our patients are coming in for allergy shots. Adding in 1 more shot is very easy. For us, it’s not an issue. We also get a lot of referrals from pulmonologists to give these drugs because we’re comfortable giving injections all the time. And we are set up to do it.
Peter Salgo, MD: OK. I heard you questioning whether people who are self-administering drugs (injectables) at home might be a good idea. Diabetics do it every day. There’s a model out there, right?
Neal Jain, MD: Because of the nature of this disease, which I think is true of diabetes, as well, people start to feel good. Do they adhere? Do they follow up? Do they keep taking their other medications? And in this population, the challenge is that this is an exacerbation-prone individual who may have been in the intensive care unit. He or she may be at risk for death from their asthma. “I’m feeling fine. I stopped taking my medicine.” Boom—something bad happens.
David Rosenstreich, MD: I think it’s a good analogy because diabetics measure their blood sugar.
Peter Salgo, MD: They do.
David Rosenstreich, MD: They’re not just giving themselves shots. “I feel better. I’m going to stop it.” They monitor themselves. We don’t have such a good way of monitoring asthma. If we did, they might be able to give themselves the injection. It’s nice to be able to follow these patients. They need a lot of other medicines, and they need a lot of advice. And so, following them is sometimes very helpful.
Transcript edited for clarity.