IL-5–Inhibiting Agents Mepolizumab, Benralizumab, and Reslizumab

Peter L. Salgo, MD: All right. Let’s talk about some other options, since you brought this up.

Don A. Bukstein, MD: Yes.

Peter L. Salgo, MD: We’ve got—I’m going to read these because I don’t want to mispronounce them, although I may—mepolizumab, benralizumab, and reslizumab. What is the pathway of these human monoclonal antibodies against IL-5? What are these drugs?

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: We’re talking about drugs that block IL-5. The IL-5 is known for recruitment of neutrophils—or am I getting...

John J. Oppenheimer, MD: Eosinophils.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Yes, eosinophils. Where am I getting neutrophils? It was originally studied years ago, primarily in hypereosinophilic syndromes; I think there was a study in eosinophilic gastroenteritis and idiopathic eosinophilia many years ago.

And then they finally got approved for asthma more recently before an indication for these rarer conditions. I think, personally, it works better—it works in about 20% of patients with asthma—but it makes a very dramatic effect on the persons who had this hypereosinophilic phenotype.

Don A. Bukstein, MD: You know the steps. Initially we did the studies; John knows—I remember he did some of the studies. We did the studies, and we made a mistake. We did them in all patients with asthma, and we saw no effect at all. And then somebody got smart. Dr. Brown did it over 100 years ago—he started looking in the microscope at people’s blood and sputum and said, “Hey, you know, it seems to work better in people who have a lot of the eosinophils.” So he went back and studied this in people who had high eosinophils. And in fact, it works OK if your eosinophils are in the 150 to 200 range, but it works really well if there are 300 or 400.

And so, for patients who have high eosinophil counts, these drugs that affect the IL-5 pathway that recruit eosinophils work very well. Benralizumab has an ultimate effect on them. It actually affects their apoptosis so that it decreases your eosinophil count basically to 0. Certainly the patient I describe may have a high eosinophil count and benefit from these drugs. Each drug has a different kind of dosing and administration, and reslizumab has to be given intravenously at a healthcare setting.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Which is us.

Don A. Bukstein, MD: And it may be that’s a good one if you’re weight based.

John J. Oppenheimer, MD: Yes. There’s a study that shows if you’re obese, you’ll fail some of the other ones, and you actually will do well with giving it because it’s a weight-based drug. None of the others are weight based; they’re all standard.

Don A. Bukstein, MD: So that may be a factor. One of them, benralizumab, you give once a month for 3 months, but then you can go every other month. OK? Every 8 weeks. So that’s a really attractive thing for some patients. And mepolizumab has been around for a long time. It has an indication for other eosinophil syndromes like Churg-Strauss disease, which is a vasculitis. So things that have very high eosinophils work well with nasal polyps and other kinds of phenotypes of asthma. So, again, each has its own little niche, but in the end, there’s huge cross-reactivity in the sense that patients will respond.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: A lot of people don’t realize there’s probably a connection between this. Some people think it’s an epidemic. But there’s evidence that it isn’t; it’s been there, eosinophilic esophagitis. We think of it as the allergic rhinitis of the sore throat, and it actually can be very challenging to manage these patients. And there is some evidence that this class of drugs may be very effective.

Peter L. Salgo, MD: Does this class of drugs have any place at all in the treatment with noneosinophilic acid?

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: I don’t think we know.

John J. Oppenheimer, MD: If you look at the efficacy, it significantly diminishes as the eosinophil count goes down. Is there somebody out there who might respond? The answer is probably yes, but I don’t think that it’s robust enough, considering the expense, to use it in that population.

Louis Christos, RPh: Well, even dupilumab took all-comers but didn’t show any benefit in patients less than 150. Correct.

John J. Oppenheimer, MD: They showed less robust efficacy. Certainly if you move up.

Louis Christos, RPh: It wasn’t a statistically significant difference.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: But these clinical trials are not that large. I mean, we’re talking about 300-some patients. It’s different if there were 10,000, but it’s harder to get nitpicky about 150 versus 300.

Louis Christos, RPh: Well, unfortunately we have to go with the data that are presented.

Don A. Bukstein, MD: You have to go with the FDA approvals. But I think dupilumab is a good example. Often there are comorbidities and that sort of thing associated with it, too; maybe atopic dermatitis. In the past, it’s been very difficult to use omalizumab for atopic dermatitis because the Ig [immunoglobulin] levels are very, very high, and you’d have to give a massive amount of drug, which would be way too expensive.

Linda S. Cox, MD, FAAAAI, FACAAI, FACP: It was actually first indicated for atopic dermatitis.

Don A. Bukstein, MD: Right. So if you are a patient with asthma who has atopic dermatitis, dupilumab may be the one to go to.

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