Biomarkers in Shifting the Treatment Paradigm of Asthma - Episode 11
Transcript: Thomas Casale, MD: I’ll open this up to all 5 of you because sometimes this question comes up, and there’s always a debate. I’ll start with Shahzad. What level of blood eosinophils makes you think that this patient has eosinophilic-driven disease and would convince you to try an IL-5 [interleukin 5] blocker?
Syed Shahzad Mustafa, MD: Nothing in life is binary. We’ve all agreed that as your levels of eosinophils increase, your likelihood of response to anti—IL-5 agents or any of these 5 FDA-approved biologics increases. In my office where there’s so many comorbidities with asthma, you can have atopic dermatitis, allergic rhinitis, we often see some peripheral eosinophilia in our patients. The lowest levels that have been FDA approved, as everyone here knows, are about 150 peripheral eosinophils that you actively have. As that number gets higher and higher, your number needed to treat, or your hit rate, gets better and better. When you get into levels of 400, 500, and above, I agree with Mike, you start leaning toward an anti–IL-5 agent.
I’m going to make 2 points about how to choose these biologics, which all seem to be better used in people with higher eosinophils and all seem to be in the Th2-high space. Two very important points are thinking about patient comorbidities. Stan started with anti-IgE, which may be very nice to couple with allergen immunotherapy, which may be useful in some patients with asthma. And an allergist would consider that, or sinus disease, or other comorbidities. I think being thoughtful about comorbidities in addition to asthma may help us down the path of 1 biologic over another. Mike mentioned shared decision-making about administration, home administration, and interval of administration.
The other small point, for myself as an allergist who sees individuals of all ages, is what ages they’re approved for anti-IgE omalizumab is approved for children as young as 6 years, as is mepolizumab. Two biologics, benralizumab and dupilumab, are approved 12 years and older, and reslizumab is approved for 18 years and older right now. I think being a little bit thoughtful about comorbidities and potentially the age of your patient may help with these very murky waters of how to pick 1 of these 5 agents for patients with severe asthma.
Thomas Casale, MD: I think you made a very good point and just want to reiterate that. If we’re saying that a lot of these disorders manifest with elevated blood eosinophils, all 5 of these biologics work better with high eosinophils. Looking at certain comorbidities and the effectiveness of those drugs in treating them, if we look at omalizumab first, we know that it’s been shown to work with allergic rhinitis. It works with chronic urticaria, but that’s not a comorbid condition with asthma. It can be used in conjunction with allergy immunotherapies. And, recently, it’s been shown to work well in patients with chronic rhinosinusitis with nasal polyps.
Dupilumab has an indication for atopic dermatitis, which often tracks with allergic asthma and has an indication for patients with chronic rhinosinusitis with nasal polyps. Then, all 3 of the IL-5 blockers are being explored right now...for chronic rhinosinusitis and nasal polyps. So, we don’t know what the data will show, but I suspect they may all have positive responses. But it is important to look at those.
Let me ask all of you another question that I think is probably important in picking these biologics. We talked about comorbid conditions, but what about individual patient characteristics, and what are you trying to achieve with that biologic? Whenever you put someone on a biologic, you have to have a reason, right? Are you trying to reduce exacerbations? Are you trying to improve quality of life? Are you trying to improve lung functions? Are there differences between the biologics and those responses?
Michael E. Wechsler, MD, MMSc: I think that every patient is a little bit different, so you have to individualize the care to every patient and consider why you want to start a biologic. Is it because on top of inhaled steroids and LABA [long-acting β-agonists] they’re having frequent exacerbations? Is it because of frequent symptoms? Is it because their lung function is low, accompanied by some symptoms? Is it because they’re on oral corticosteroids and you want to get them down to lower-dosed corticosteroids? Each of these drugs has benefits with regard to all those outcomes. We want to try to identify people who are responders with regard to all those different outcomes and even super responders across multiple domains.
One of the challenges...we have as clinicians is that there aren’t any head-to-head studies comparing the biologics, 1 to the other. We don’t have a lot of guidance, so every patient is like an N of 1 study. We’re hoping for the best. We’re putting stock into the biomarkers. We’re putting some stock into the comorbidities. We’re putting some stock into the predominant outcome measure. In reality, we don’t have a good idea when we start someone on a specific biologic how well he or she is going to respond to that biologic. That’s, I think, a major challenge for us.
Syed Shahzad Mustafa, MD: Of course, we want to make our patients feel better and improve quality of life. But, again, I think as this pristine group who are a part of so many of these studies knows, the primary endpoint on most of these studies was steroid-requiring exacerbations. That’s generally where I think many of us are pulling the trigger—when they’re on combo agents, multiple medications, and still ending up on systemic steroids frequently.
Before that, we want to be a little cautious about the timeline of response. I think it’s important that some of these biologics do have a little bit of difference in cadence of how quickly you expect to see improvement in an individual. We don’t want to rip through them too fast. We want to give them time to work. If you’re looking for a decrease in steroid-requiring exacerbations, I think clinicians may want to let it ride for a little bit longer to see where we get, rather than kind of blazing through them every couple of months and calling them biologic failures. I think that’s an important point. Obviously, symptom control but, again, steroid-requiring exacerbations really remains the driving force for many clinicians.
Thomas Casale, MD: That’s a great point because when we look at the patients [who] were enrolled with a lot of these trials, they may have had the history of 2 previous exacerbations in the previous year. Almost every biologic shows about a 50% reduction. How long do you have to follow a patient if you’re just using exacerbations to say it went from 2 to 1? It’s difficult.
Transcript Edited for Clarity