Identifying the Biomarkers for the Treatment of Severe Asthma - Episode 11
Neal Jain, MD, FAAP, FAAAAI, FACAAI: Nic, I’m curious to know what your thoughts are. You’ve published some data on this, with regard to what biomarkers might be helpful in identifying patients who are responsive to omalizumab.
Nicola A. Hanania, MD, MS: Well, Neal, in the clinical trial arena, we published a couple of papers looking at this specific question. One is an analysis of the EXTRA study. As you know, this was a study looking at omalizumab added to ICS/LABA [inhaled corticosteroid/long-acting beta agonist] in the high-risk population. It sounded like the high blood eosinophil at baseline, high FeNO [fractional exhaled nitric oxide], T2 [type 2] biomarkers, suggested better response in reducing exacerbation. We also looked at periostin, which is not a biomarker available yet. And then when we looked at the pivotal studies with omalizumab, we sort of replicated the blood eosinophil prediction, but also the severity of the disease. Patients on LABA, on higher-dose inhaled steroids, with a history of hospitalization tend to have a better effect. That was in a clinical trial, but I know Brad had done some work with real-world studies.
Bradley Chipps, MD: There was a recent article in European Respiratory Journal looking at almost 80% of the patients in France on omalizumab, and the response was agnostic to their baseline eosinophil level. So even though I’ve published data previously that in the pivotal trials, the analyzed rate of exacerbations was more effectively decreased with the higher eosinophil counts, a more critical look at this over a 52-week period suggested that the eosinophil count was not a major predictor. So I think to Nic’s point, the jury is still out.
Neal Jain, MD, FAAP, FAAAAI, FACAAI: The jury is still out. Aidan, do you have thoughts about this?
Aidan A. Long, MD: No, I think these are the 2 experts on that topic.
Neal Jain, MD, FAAP, FAAAAI, FACAAI: I would agree. You guys have published a lot on this data. Discuss Xolair’s place in the treatment algorithm based on pathophysiology. Knowing that we don’t really know, maybe there are some biomarkers that are predictive, and maybe there aren’t. In the severe population that has more exacerbations, maybe it’s more helpful? But then we see some data that say that in the really severe population, maybe it’s not helpful. What is its place?
Nicola A. Hanania, MD, MS: Well, I don’t think the data say that in more severe it is not helpful. But in the PROSPERO and the French study that Brad alluded to, baseline blood eosinophil does not seem to be a predictor of response—ie, whether a patient has high blood eosinophil or not, they have a response to omalizumab. In my mind, omalizumab works best in the allergic phenotype patients. There are some case reports, case series of its use in nonallergic patients, but I don’t personally use it in that group. But certainly, patients who have perennial allergies, have failed ICS and LABA, and continue to have exacerbations—those are the classic patients who would fit the omalizumab criteria. It doesn’t matter what their eosinophil or FeNO level is. This is the type of patient who would....
Bradley Chipps, MD: As Aidan said a moment ago, it’s those patients who have the IgE [immunoglobulin E] in the right bracket, who have a positive skin test, who have that driving their symptoms, who are most effectively handled with omalizumab.
Aidan A. Long, MD: I would agree with that, and I think it speaks to the fact that maybe omalizumab is a bit more broadly allergic in the Th2 [T-helper cell type 2] phenotype than say the anti—IL-5s [anti–interleukin-5s]. That seems to be a more restricted group. But clearly, the need for allergy, the need for IgE with specific activity, needs to be there when choosing that drug.
Bradley Chipps, MD: Because for the IL-5s, if I gave you the Dr. Patrick Flood-Page paper and said, “Do you think this is going to work,” You’d say, “No.”
Aidan A. Long, MD: Exactly right. I think omalizumab is a bit more broadly active, and I think perhaps we’ll find that with dupilumab and some of the biologics yet to come.
Neal Jain, MD, FAAP, FAAAAI, FACAAI: Right, exactly.
Transcript edited for clarity.