Peter L. Salgo, MD: Let’s discuss omalizumab. Now that’s FDA approved.
Don A. Bukstein, MD: Yeah. Omalizumab was the first; it’s been around.
Peter L. Salgo, MD: And what is the indication for it?
Don A. Bukstein, MD: It has been around 16 years.
Peter L. Salgo, MD: 16 years.
Don A. Bukstein, MD: It’s moderate to severe. And I’ll make a comment here. When that was first studied—we did some of the early studies—it was a more moderate/less-severe population than many of the other studies. There’s an article that looks at the mepolizumab population compared to the omalizumab [population]. And it’s definitely a more severe population, an older population. So there’s a difference in the population studied. But it was a moderate to severe asthma that had to have a positive skin test, usually to a perennial allergen, such as dustmites, cockroach, mouse allergen.
Don A. Bukstein, MD: And people have to have an IgE [immunoglobulin E] level, and this was kind of chosen because that was the range of most IgE levels that we saw that had positive skin tests of 30 to…
And it goes up to 1,300 in children; it was 700 in adults. So, again, you’re seeing it has to have a high IgE, positive skin test, moderate to severe disease. When the first studies were done we didn’t even have combination therapy so they were done with just inhaled steroid alone, medium and high dosed. And then we did them with combination therapy. And there are some studies with more severe. There have been hundreds and hundreds of studies over the last two decades with omalizumab. So it’s the best study, no question. And when we first started studying it we didn’t see side effects. But after a while we saw that a certain percentage, with a foreign protein, had anaphylaxis. So one of the problems is that although we know, if you want.
When you talk to the patient you have to tell them that this is a risk, anaphylaxis, that you’re going to have the possibility of systemic reaction. You explain to them, you get some program with them that they’re going to wait a certain amount of time, and you talk to them about epinephrine, an autoinjector of some type. But what’s most important, you try to get them risk assessment. And we know that people who are going to have anaphylactic reactions usually have had them before, almost 50%.
So, again, it’s a very low percentage in patients. Some were probably below .1%, which is very low. We haven’t had deaths from omalizumab for these systemic reactions, but it’s certainly a risk factor. Initially there was some concern about malignancy. That’s been dispelled. And more recently there’s been some concern about cardiovascular events, also seems to have research that suggests that that’s not necessarily the case.
Peter L. Salgo, MD: Now what is the mechanism of action before we go further.
Don A. Bukstein, MD: It interrupts the binding of the allergic antibody, IgE, to mass cells or basal cells. So if they can’t bind together and crosslink and get mediators or cytokines released, then you don’t get the allergic reaction and inflammation.
Peter L. Salgo, MD: And what biomarkers do you look for using this drug?
Don A. Bukstein, MD: With XOLAIR, omalizumab, you usually follow; you can follow FeNO. That sometimes is a very good biomarker. It will stay up in your patients before they may even be on oral steroids or inhaled steroids and not going down. You put them on omalizumab they decrease. Besides that, we really don’t have a great biomarker. IgE is of no use once you get one determination. So you can follow the eosinophil counts, they also decrease, but they don’t go down to zero like they do with some of IL-5s; they do go down. So the eosinophil counts to a degree exhale nitric to a degree, but we don’t have a perfect biomarker.
Linda S. Cox, MD, FAAAI, FACAAI ACP: Well, we might, but nobody’s really looked at it. First of all, one of the other requirements is that they are allergy skin, or skin blood tests.
Don A. Bukstein, MD: Yeah, that’s what I said.
Linda S. Cox, MD, FAAAI, FACAAI ACP: Right. But omalizumab knocks out a skin test response. I could have somebody who has a huge pricked skin test to dust mite and three months later, gone, which is pretty impressive.
John J. Oppenheimer, MD: From a payer perspective, two things worth mentioning is we talked about the requirements of having a skin test and weight, normogram based upon weight and IgE. But, again, as we pointed out, if you enrich the population with elevated ENL, you’re more likely to respond. And here’s something really interesting about this drug. They did a study. We know that September is a time of known exacerbations.
Linda S. Cox, MD, FAAAI, FACAAI ACP: This is important.
John J. Oppenheimer, MD: So Teach-It-All showed that if you actually, to give it before September, that epidemic of asthma, and just treat it early into the fall and the early winter, you could actually diminish exacerbations by it.
Don A. Bukstein, MD: So omalizumab also has an activity that’s antiviral, there’s no question. It probably works through, again, interferon, but we’re not completely certain of its antiviral, but this study really suggests that pretreatment before that with children, most of their exacerbations and hospitalizations comes in the month of August, September, and October when they go back to school. And you have this huge swell of exacerbations, ER admissions, hospitalization. This study, for the first time we saw that flatten, completely disappear, as John so aptly put. And that’s an exciting thing because now we’re seeing the interplay between allergens and viruses, and viruses are the major precipitator.
John J. Oppenheimer, MD: With real outcome difference.
Peter L. Salgo, MD: Who would be the idea patient for that drug, patient factor?
Don A. Bukstein, MD: An ideal patient?
Peter L. Salgo, MD: Yup, for this one, omalizumab.
Don A. Bukstein, MD: I think it would probably be someone with not real severe disease. In every study with omalizumab, milder disease seemed to respond better. So the real severe patients on daily oral steroids, we weren’t even able to see a statistically significant decrease in hospitalization ER visits. But they did lower the amount of medication they’re on. So it would be somebody on a lot of medication, maybe lava, inhaled steroid and anticholinergic often times, that’s still having exacerbations, burst of steroids, more than one or two a year.
They probably have upper airway disease. They probably have allergic rhinitis, maybe nasal polyps, maybe something else. But you’ll find out when we talk about some of the others, they may even be more active against nasal polyps. They have a high eosinophil count, a high ENO. They have positive skin tests to the zero allergens, okay? And you go over and share decision making all their options and they say, “I’m a conservative kind of guy. I like a drug that’s been around a long time. I know its side effects. And cautious, I’m very cautious.” So that may be; they know themselves better than I know them, and they’re going to say, “That’s the perfect drug for me.” But I’m going to tell you something, I offer them the other options. I don’t decide for them.