Biomarkers in Shifting the Treatment Paradigm of Asthma - Episode 9
Transcript: Thomas Casale, MD: Mike, you’ve done some work on the IL-5 [interleukin 5] blockers, and we have 3 of them: mepolizumab, reslizumab, benralizumab. When would you pick an IL-5 blocker over omalizumab or dupilumab?
Michael E. Wechsler, MD, MMSc: I try to identify what’s most prevalent, the highest biomarker, in a given individual. Sometimes that can be challenging. If someone has low nitric oxide, lower IgE [immunoglobulin E] levels, and a high eosinophil count, then it’s very easy. I think the higher the eosinophil counts, the more likely I am to use an anti—IL-5 therapy. I don’t think you’d be wrong in choosing an anti-IgE therapy or an anti–IL-4/IL-13 therapy in those patients. It seems to me that the predominant biomarker is the eosinophil, and you should probably target that.
Now you could target that by giving anti—IL-5. You can target it by targeting the IL-5 receptor. You could give dupilumab, which targets eosinophil trafficking because both IL-4 and IL-13 are involved in eosinophil trafficking. So I don’t think you’d be wrong with any of those approaches. We know that patients who have higher levels of eosinophils tend to respond very well to the anti–IL-5 therapies.
Now, in someone whose eosinophil counts are really about 1000, that’s where I’m a little bit less likely to use an anti—IL-4/13 approach because when you give anti–IL-4/13 and you block the eosinophils from getting into the tissue, you might see a rise in the eosinophilic counts. And that doesn’t necessarily correlate with any safety signals, but it will give someone pause if the eosinophilic count rises. Usually, that increase in eosinophilic count can be transient and may come down over time. I’ll use the eosinophil count as the primary guide in terms of determining anti–IL-5 or anti–IL-5–receptor therapy.
We have 3 therapies available, and they all have different attributes that may make you want to use one over the other. Mepolizumab has the longest history and is now available for at-home use, in addition to in the office. It’s given on a monthly basis. I think the fact that it has the longest history gives some people some support to use that, and it alleviates some concerns because it’s been approved now for almost 5 years.
Reslizumab is an effective therapy, as well. In fact, the improvement in FEV1 [forced expiratory volume in 1 second] in those patients seems quite demonstrable, as well as the reduction in exacerbations. It’s an intravenous [IV] preparation, which has benefits because you know that it’s getting...where you want it to go. On the other hand, there are some complexities in terms of giving IV therapy. It is dosed based on body weight. For patients who have higher body weight levels, that might be a good choice for them.
The third option is the IL-5 receptor alpha antagonist benralizumab. Benralizumab is a good therapy for several reasons, not only does it block the receptor and prevent IL-5 from binding there and activating eosinophils, but it also may be involved in some mediated cytotoxicity and deplete the eosinophils. Another advantage of benralizumab is that after the first few doses, it can be given every 8 weeks. It can now be administered at home as well. There are several advantages.
All these anti—IL-5 therapies are somewhat comparable in terms of their efficacy. They’re all relatively safe therapies, and they’re all effective, well tolerated, and help reduce exacerbations—both in patients we’ve got on inhaled corticosteroids, but also the studies looking at mepolizumab and benralizumab in particular, as well as some post hoc analyses of reslizumab, suggested there’s efficacy in patients on oral corticosteroids.
Transcript Edited for Clarity