Managing Asthma With Biologic Therapy

Neal Jain, MD, FAAP, FAAAAI, FACAAI: We’ve heard about all of these different biomarkers. We’ve heard about guidelines. We’ve heard about difficult-to-treat versus severe, uncontrolled. What is the current place for these biologics in the guidelines? Where do they fall into our realm? You talked about not exacerbation-prone. So when is it that we use these different therapeutics, according to the guidelines?

Bradley Chipps, MD: Well, again, we have to take a step back. All of the currently available drugs are approved upon decrease in exacerbations. That’s the low-hanging fruit. As we said before, you pick the comorbidities that are causing the patient the most problems, and what drug you think would most efficiently attack that. And then the rest is insurance coverage, phase of the moon, which way the wind is blowing, and all of the important determinants like that.

Nicola A. Hanania, MD, MS: I know there are no head-to-head comparisons, but the patient populations in different studies were different. With omalizumab, in very old studies, when it first actually was studied, it was on patients on inhaled steroids; whether they were on a LABA [long-acting beta agonist] didn’t matter.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: It was more of a moderate population.

Nicola A. Hanania, MD, MS: And it worked in the allergic population. It reduced exacerbations—maybe not to the extent that we’ve seen in the mepolizumab data, but the mepolizumab studies, or the anti—IL-5 [anti–interleukin-5] studies recruited patients with 2 or more exacerbations with high blood eosinophil levels. So it’s a totally different population.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: A very severe population.

Aidan A. Long, MD: Exactly. Right.

Nicola A. Hanania, MD, MS: Coming back to dupilumab data and the studies, they actually recruited moderate to severe. They only had to have 1 exacerbation. So it’s probably a less severe patient population than the anti—IL-5.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Other than the oral steroid dependent.

Bradley Chipps, MD: That still showed a bigger signal for exacerbation reduction with dupilumab.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: I try to figure out if there is a difference. I’m curious to know your thoughts. I sort of look at what the background rate of exacerbations drop to in these trials, at least when you’re looking at a population who is on a moderate to high dose of ICS [inhaled corticosteroid]/LABA. And I think that’s where you start to see that maybe there is some comparison there. I’m curious to hear your thoughts on that.

Aidan A. Long, MD: It clearly isn’t zero.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Right, it doesn’t measure up to zero. Absolutely.

Aidan A. Long, MD: And if it’s 2 a year with a 50% reduction, well, that’s 1 a year. That’s going to be hard to measure in 6 months.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Right.

Nicola A. Hanania, MD, MS: But there’s no question that the anti—IL-5s show that the higher the exacerbation at baseline, the better the effect. We’ve shown a similar thing with an omalizumab post hoc analysis. Although we didn’t have the history of exacerbations, through the pivotal studies recorded, we looked at the use of a LABA and hospital admission the preceding year. We had that data. It tends to be that in the more severe patients, and obviously they’re at higher risk of exacerbation, the reduction is more pronounced.

Bradley Chipps, MD: One of the IL-5s just reported an enhanced paradigm—nasal polyps, FVC [forced vital capacity] less than 65%, and 3 or more exacerbations a year all predicted an enhanced response to that anti—IL-5. So I think that’s an important thing to keep in mind.

Aidan A. Long, MD: To get back to your question, where do they fit into the guidelines? They fit in the severe end of it. When you have tried, as we’ve all discussed, a step-up paradigm, once you’ve tried everything else, that’s where they fit. And I think that’s driven largely by economics. If there was not an economic factor, we may start parsing these out a lot earlier in the pathway. But because of economics, it’s at the end when nothing else works, when all the cofactors we spoke about—adherence, and comorbidities, and adverse environment, or misdiagnosis—have been excluded, that’s when you start using them.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: This has been super informative. I have appreciated and enjoyed having this discussion with all of you. Before we end the discussion, I want to get some final thoughts from all of you about the use of these therapies, about biomarkers, about where you think we’re going. Nic?

Nicola A. Hanania, MD, MS: Thank you for having me, Neal. I certainly enjoyed the discussion. I think it’s an exciting time for patients and for clinicians like us who treat severe asthma. I think we’re seeing more and more opportunities. We no longer think about it as this disease that fits all. At least we think we know how we subdivide asthma. I think the biomarker field is expanding. There is more to come, which will allow us to tailor therapy. That’s the whole thought of precision approach to managing asthma. We’re not there yet, but we’re getting there, slowly. I think the use of these biologics we have now will help a lot of patients out there. Trying to figure out which one to use is still a management dilemma, I think. In my mind, the more the merrier. The more options we have, the better. But certainly, we would like to do more work to try to decipher which one would be best for which patient. I think that’s still ongoing.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Brad?

Bradley Chipps, MD: Well, I think the obvious low-hanging fruit we discussed earlier: Omalizumab, for younger patients or patients with hives; IL-4/IL-13, nasal polyps, and atopic dermatitis. Clearly that’s a low-hanging fruit. I think the bigger question is in the anti—IL-5 space. What predicts a more robust response is clearly a higher eosinophil count in the peripheral blood compartment to begin with. I think enhanced response, as I’ve mentioned, the study that was most recently published shows us that, again, the patients who have more sustained disease-activity signal tend to respond well to that. But remember, the IL-4/IL-13 drug is the only drug that has OCS [oral cortiocosteroid] in their package insert.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: More to come, right?

Bradley Chipps, MD: Right. That’s why we have a job.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Exactly.

Aidan A. Long, MD: I actually would echo the comments of my colleagues at the table. It’s been a very exciting discussion. We’re going to learn a lot more about these. We’re at the beginning of this journey. We’re going to learn how to use them, in whom to use them, and when to use them. We’re going to learn about the disease that we think we understand. It’s going to tell us more about the stuff we don’t understand. I think it’s a really exciting time.

Bradley Chipps, MD: I think it’s more important to think about what we don’t understand and try to find those answers.

Neal Jain, MD, FAAP, FAAAAI, FACAAI: Exactly, yes. Finding the questions in these solutions is definitely, I think, part of it. So thank you all for your contributions in this discussion. On behalf of our panel, we thank you for joining us. We hope you found this Peer Exchange discussion to be useful and informative. And with that, we’ll conclude.

Transcript edited for clarity.