Food Allergy and Your Kiddo

Is Xolair (omalizumab) really "superior" to multi-food oral immunotherapy (OIT)?

• Alice Hoyt, MD, and Pam Lestage, MBA • Episode 82

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The world of food allergy treatment has been buzzing with headlines claiming that Xolair (omalizumab) is "superior" to oral immunotherapy for treating multiple food allergies. As a board-certified allergist who both prescribes Xolair and performs multi-food OIT, I'm here to cut through the hype and provide clarity on what these treatments actually offer.

Let me take you behind those headlines to examine the OUtMATCH study that sparked these claims and we will decide whether Xolair truly is superior to OIT.

Links I mention:

Here is the Food Allergy Peds Hub article on this topic, which has the graphic I mentioned.

Here is a link to Dr. Platts-Mills' amazing article. 

Regarding OUtMATCH stage 2, the study results are not published (at the time of this publication - my info came from the presentation at the AAAAI 2025 and the photos I snapped of the presentation of the data). Here is the NIH link I mentioned.

Here is my Doximity article on this topic.

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Dr. Alice Hoyt:

Is Xolair (omalizumab) really superior to oral immunotherapy when it comes to treating patients with multiple food allergies? That is exactly what I'm going to discuss with you today on food allergy and your kiddo. Okay, so you may have seen a headline recently. One on the NIH's website says omalizumab treats multi-food allergy better than oral immunotherapy. High rate of oral immunotherapy side effects in NIH trial explains superiority of omalizumab. That's one of the headlines. Another headline that was on the American Academy of Allergy, asthma and Immunology's website, of which I am a fellow of the Quad AI, as it's called. That headline read Omelizumab is superior to oral immunotherapy in multi-food allergy treatment study. So what is really going on here? What is Omelizumab? The brand name is Xolair X-O-L-A-I-R. The brand name is Xolair. What is that? And what is really multi-food oral immunotherapy or OIT, and is one truly better than the other?

Dr. Alice Hoyt:

I recently wrote about this on the Food Allergy Pediatric Hub, which is a food allergy focused clinician pediatrician website where I try to provide evidence-based information, of course, to my colleagues who serve families who have food allergies, treat kiddos who have food allergies, but are not they themselves allergists? So general practitioners, really any clinician who wants to know more about what's going on in the world of food allergies, but they themselves are not an allergist, so I wrote about this there. I also was asked by Doximity, which is an online network of doctors. I was asked by them to write about my experience at the academy meeting, the quad AI meeting that I attended recently, where this information was presented. So this is the topic that I selected because hello, when you hear a headline like that that one treatment approach is superior to another treatment approach I mean wow, superior is a really strong word, especially when we're talking about treatment approaches and, spoiler alert, one treatment approach is not superior to another for everybody, right? I mean, in 99.999% of cases, of all things medicine, we need to personalize the approach, and one treatment option for one kiddo is not going to be superior to a different treatment option for another kiddo. So, but why? Why was this, in my opinion, very strong claim made and do they have the data to really back up such a large claim? I do not think they do and I'm going to tell you why, and full disclosure I prescribe Xolair. I also do multi-food oral immunotherapy. I do it all. I'm really happy that we have all these options now to really try to serve families the best way we can in the best approach for their kiddo. So what does that really mean with all this?

Dr. Alice Hoyt:

First let's talk about what is Xolair or omalizumab. Xolair is a biologic medication that is injected once or twice a month to help prevent a kiddo or adult who has a food allergy from having a severe allergic reaction should they ingest their allergen. So what Xolair is is an antibody that actually binds to the allergic antibody. Allergic antibodies are called IgE, immunoglobulin E. I call them allergic antibodies. They're not just allergic antibodies, they do other important things.

Dr. Alice Hoyt:

But for whatever reason, in the last few hundred years we as humans have started making allergic antibodies or IgE, specific to foods like peanut, like cashew, like milk, and in these last few hundred years we've had the onset of allergic conditions. I'll put a link to one of my favorite papers by Dr Thomas Platts Mills, who was one of my mentors at the University of Virginia Wahoo Wah, where I completed a three-year allergy fellowship. Dr Platts- Mills is a grandfather of allergy and he wrotea beautiful paper a few years ago, really discussing the onset of allergic conditions. If you were to come see me in my office I would probably use a line along the lines of Job had a lot of bad things, but he didn't have food allergies. That's because really allergies did not come on the scene until just a couple hundred years ago, and food allergy in particular.

Dr. Alice Hoyt:

The uptick in food allergy was first noted in the 1990s, and really just in the 1900s was when we really started even seeing this thing called anaphylaxis to foods. So why we as humans have started making IgE to foods, we really don't know. But here we are. We are in a place where we make IgE to foods and kids now can have food allergies. Five to 10% of kids, depending on the study you read, have an anaphylactic food allergy. So what's really going on with that and how can we treat it?

Dr. Alice Hoyt:

Well, that comes back to the whole topic of today. Right, like, what about Xolair? What about OIT? Is one better than the other? Back to what Xolair is.

Dr. Alice Hoyt:

Xolair is an antibody that's going to bind to the allergic antibodies, whether it's peanut, cashew, whatever it is. It's going to bind to all those allergic antibodies that are floating around in a person's bloodstream and it's going to allow the immune system to sort of dispose of those antibodies so that they are no longer able to really hang out on allergy cells. And if those allergic antibodies are not hanging out on your allergy cells then it's really hard to activate those allergy cells because it's those allergic antibodies that bind to the allergen and then trigger that allergy cell to then activate. So you can see an example a kiddo who has a peanut allergy. They have peanut specific IgE or peanut allergic antibodies hanging out on their allergy cells, their mast cells and their basophils when they eat peanut.

Dr. Alice Hoyt:

Peanut protein binds to the allergic antibody that's hanging out on the allergy cell and that binding ultimately triggers that allergy cell to become activated, specifically to degranulate the granules within that cell get kind of spewed out the contents of those granules, which is histamine, vasodilators vaso meaning vessel, dilate, meaning open up. That's why kiddos and adults who have anomaloxis can have a drop in blood pressure. It's because of what's in the granules of the allergy cells, also bronchoconstrictors bronco meaning our airways constrict, meaning get smaller Bronchoconstrictors are in the granules. So when those allergy cells get activated that's how an anaphylactic reaction can occur is because the contents of the granules is being spewed out locally into the tissues, into circulation, and the treatment for that is epinephrine. Epinephrine binds to the allergy cell, stabilizes it, tells it hey, stop having this terrible reaction. Also binds to the blood vessels, tells them to tighten up so that we can combat any drop in blood pressure, we can combat swelling, we can combat the histamine effect, all the things. So epinephrine is your treatment for anaphylaxis.

Dr. Alice Hoyt:

Xolair binds those allergic antibodies, kind of takes them out of circulation. So then if you don't have the allergic antibodies on the allergy cell anymore and you accidentally eat a peanut, well, that peanut doesn't have a way to trigger the allergy cell. Amazing, amazing, that is amazing. That is amazing because it having Zolair approved to prevent anaphylaxis when it comes to kiddos and adults with food allergies, it now provides many families an amazing safety net so that if their child were to accidentally ingest their allergen, then they won't have a severe allergic reaction. It is amazing.

Dr. Alice Hoyt:

Xolair itself is not a new drug. It was approved last year by the FDA as a management tool as a treatment of food allergy by preventing anaphylaxis from accidental ingestions. But Zoller itself. We as allergists have been using Xolair for 20 years. It helps people who have asthma, it helps people who have chronic hives, it helps people who have nasal polyps, allergic rhinitis, because it's the anti-IgE, it's the anti-allergic antibody, so it helps lots of allergic conditions. It's really fantastic. So, as you can see, like I'm not an anti-zolair person, I think zolair is great.

Dr. Alice Hoyt:

There was a generic recently made available or a biosimilar that we'll talk about on a different episode. Made available Like this is good. It is good to have this option, but it comes back to is this option better than oral immunotherapy and why is this study called the OUtMATCH Study? Why is this study saying that it is better? Well, let's talk a little bit now about what OIT is. I've talked about OIT multiple times on the podcast. I've had amazing guests on the podcast talking about OIT.

Dr. Alice Hoyt:

What OIT is, or oral immunotherapy, is a treatment plan for food allergy anaphylactic food allergy where over time we give the kiddo or the adult small amounts of their allergen. They take it every day and then we increase that every few weeks until we get them to a maintenance dose. Once they're on a maintenance dose so a maintenance dose of peanut for a peanut allergy might be half a teaspoon of peanut butter we keep them on that, recheck their labs After 6, 12 months, see if we've driven down their allergic antibody level and see also how well have they been tolerating their dose. Do they like it? Do they want to eat more of it? Have they had accidental ingestions of eating a whole lot more of it? All the clinical indicators of tolerance, before we then say, okay, well, let's do a full dose challenge and see if you can eat two or three tablespoons of peanut butter.

Dr. Alice Hoyt:

That is oral immunotherapy, where we introduce the allergen in low amounts and slowly increase the amount over time, teaching the body to tolerate a food. Now that tolerance, while it has something to do with IgE, over time the IgE level will go down. At first, actually, the IgE level kind of pops up because when a kid is being exposed to their allergen, their immune system is recognizing it and immunoglobulin production will initially increase. But the way OIT works is by actually accessing a different part of the immune system, a part of the immune system that involves regulatory T cells, and I won't go down the stream of an immune lecture right now. But ultimately OIT is accessing a different compartment of the immune system and it is growing tolerance to the food and that development of tolerance over time will overcome in most cases. Right, no treatment is 100% for everybody, but in most cases over time we're able to grow tolerance to a food in amounts that will make a kiddo at least bite safe amounts that will make a kiddo at least bite safe, meaning if they were to accidentally eat a bite of a peanut butter cookie they wouldn't have a severe allergic reaction, whereas before starting the treatment, if they were to accidentally take a bite of a peanut butter cookie they could have a severe reaction. So OIT is going to build tolerance to a food. So OIT is going to build tolerance to a food.

Dr. Alice Hoyt:

Now, is OIT a better treatment than omelizumab or Zolaire? Well, let's talk about that. In this study what was compared was omalizumab and a placebo version of oral immunotherapy. That was one treatment arm. The other treatment arm was placebo, omalizumab or placebozolair and a true multi-food oral immunotherapy, a true multi-food oral immunotherapy. Now, the issue with this and I will put a link in the show notes to the visual that I created both for Doximity and then also on the Food Allergy Pediatric Hub article I mentioned to you is that the oral immunotherapy protocol that was used in Outmatch was incredibly aggressive. What do I mean by aggressive? Well, I mentioned earlier when I talked about how do you do OIT, that OIT is low amounts of the alleralforzia protocol.

Dr. Alice Hoyt:

Palforzia is the FDA-approved oral immunotherapy product that treats peanut allergy. It is defatted peanut flour. The way Palforzia works is it's these little capsules of pre-measured amounts of the defatted peanut flour. You open up the capsules and mix it into applesauce and that's how you take your dose, or that's how you give your kiddo your dose. Now, the first day of doing Palforzia you do what's called an escalation day, meaning you go into the allergist office and you start with 0.5 milligrams of the allergen, then you go up to one milligram, so of peanut protein, then 1.5, then three, then six, and then you stop, and the next day you go back and then you start with just a three milligram dose. So a lot of allergists too, if they're using peanut butter or non-Palforzia peanut powder, pb2 powder, whatever the case may be, they might start just by doing three milligrams or they might start by just giving a dose of one milligram or two milligrams. So not doing that whole escalation day, right? Really, there's not a whole lot of evidence for that escalation day anyway. That's just how the protocol has been done for a long time.

Dr. Alice Hoyt:

Palforzia is a very, very well used studies, kind of like the original sort of OIT protocol. So they start with this little mini escalation day and then the next day you start with, okay, what's gonna be the kiddo's dose for every day for at least the next two weeks, and that's three milligrams. And to put that into perspective, one peanut has about 300 milligrams of peanut protein. So basically, you're starting with around three milligrams, depending on what peanut product you're using, or if you're starting with around three milligrams depending on what peanut product you're using, or if you're using Palforzia, and then you up dose every two weeks. So the kiddo takes the dose every day the same time every day, one hour before and two hours after. They can't be doing anything that's raising their heart rate or raising their body temperature, because that can lower the threshold to have an allergic reaction. So, yes, it is a relatively intense protocol, because if you're a kiddo who runs track, who does sports, who does all these things well, it can be hard to find that pocket of time where, an hour before and two hours after, you are awake and you are not doing anything that's raising your heart rate or raising your body temperature. So that's why OIT is not the right fit for everybody. That's why we talk about things like Solaire or sublingual immunotherapy, which is a much more forgiving form of immunotherapy. So with Palforzia, with most oral immunotherapies you updose every two weeks. So in the Palforzia protocol three milligram dose, then two weeks on that, then six milligrams, then 12 milligrams, then 20, 40, 80, 120, 160, 200, 240, up to 300. And that's your maintenance dose. So 11 updoses you. You up dose every two weeks, no more, no, no sooner than that. But some families will stretch it out or some allergists will stretch it out too, depending on how well is the kiddo tolerating it. So you could see like it starts pretty small and and and goes up kind of doubles three to 6, 6 to 12, and then 12 to 20, and then 20 to 40. And this is all every two weeks. And then 40 to 80. And then it goes up by 40 until you get to 240. Then you make a little bit bigger of a jump to 300, and 300 is your maintenance dose. So that's 11 up doses.

Dr. Alice Hoyt:

Let's look at the protocol that Outmatch used as their OIT. They started with three milligrams of the allergen and then went up to 30 and then went up to 60, and then went up to 125 and then up to 250, 375, 560, 800, up to a thousand milligrams at dose number nine to 1,000 milligrams at dose number nine Now. Leading up to this, all of the kids were on and it was all kids in the study. Now the kicker about this study is that this part of the study the Zolair versus OIT this is actually stage two of the study. Stage one of the study is what got omelizumab or Zoller, approved by the FDA to prevent anaphylaxis from accidental ingestion of a food allergen. That was stage one of the study. Stage one of the study compared omelizumab to placebo. Oit was not involved in stage one. Stage one very clearly demonstrated that omelizumab does protect against severe allergic reactions when someone eats their allergen. They demonstrated this by challenging kids first to make sure that they were allergic to the food, then enrolling the kids and the kiddo either was on omalizumab or they were on placebo for 16 to 20 weeks and then they challenged them again and the kids who were challenged on Xolair. They were able to consume a lot more of their food allergen before having a reaction. The kids who were not on Xolair you didn't see that effect. So Xolair was clearly protective.

Dr. Alice Hoyt:

Stage two of this study is where they took some of those kids who were on Xolair or on placebo and then they put them all on Xolair for eight weeks and Then they stratified the kids to either start multifood OIT or placebo OIT. They all continued Xolair for another eight weeks and then the group that was on the multifood OIT got switched over to placebo Xolair. The other group that was on placebo OIT continued on Zolaire. They continued this for 44 weeks and then they repeated the food challenges and what was demonstrated was that the kids who were on the real OIT and placebo Xolair many of them did not tolerate OIT. Well, they were having reactions. Well, I'm not surprised they were having reactions because I come back to the OIT protocol that was used in OUtMATCH is significantly more aggressive than Palforzia, significantly more aggressive than other OIT protocols that are regularly used.

Dr. Alice Hoyt:

As an allergist who does a lot of OIT, I will tell you that I do not have a protocol that goes from 3mg to 30mg to 60mg to 125mg to 250mg, basically getting a kiddo up to eating a peanut with just five up doses. No way, Jose, because these kiddos are allergic. And look, when the primary investigator was asked about this at the academy meeting, that was the first question. I was so glad somebody went up there and asked about it, because if not, I was going to go ask and that's never fun to go up into these. Well, some people like to go, and you know, ask the question in front of the big old group. I don't really like to do that. I would much rather have them on the podcast. That's a great idea. I should have them on the podcast. But I digress Tangent.

Dr. Alice Hoyt:

But when he he was asked, when the primary investigator was asked like, hey, don't you think this protocol was a little bit aggressive, the response was that well, they had been on zolair so we thought that the kids would tolerate it. Well, that that's kind of the part of part of the study. And there was not a study done that demonstrated that kids can be on Xolair leading up to OIT and then better tolerate an expedited OIT protocol. So I would say that Xolair is superior to an expedited OIT protocol. But I would not say that Xolair is superior to multi-food OIT, because what they compared Xolair to in OUtMATCH Stage 3 is not multi-food OIT. It's like aggressive, super quick multi-food OIT. And if they wanted to compare it to expedited OIT, well, they should have first demonstrated that using Xolair prior to OIT allows an allergist, allows a kiddo to tolerate expedited OIT. But that was not previously demonstrated and that clearly was not demonstrated here.

Dr. Alice Hoyt:

Because why the headline is omalizumab is superior to OIT is because a lot of the kiddos didn't tolerate the OIT. They didn't tolerate it because it was so aggressive. So it's really disappointing that the study was done this way because it really didn't compare it to multifood OIT. It didn't compare Zoller to multifood OIT. The study compared Xolair to an aggressive multifood OIT. But what's interesting too is that the kiddos who did tolerate that expedited approach so about half of them the outcome with Zolaire was kind of equivalent. So in the kiddos who tolerated this expedited OIT they did about the same as the kiddos who were on Zolaire.

Dr. Alice Hoyt:

So then it comes back to well, what really is better, being on OIT or being on Xolair? Well, let's talk about that OIT. As I mentioned, it's got its drawbacks right, like an hour before, two hours after, not being able to do anything that raises heart rate, raises body temperature, that can really impact somebody's life. Also, even with Palforzia, with the protocol that I mentioned in the Palforzia study, like 14% of those kids had anaphylaxis to the OIT, like Palforzia itself is not necessarily like an easy breezy OIT protocol.

Dr. Alice Hoyt:

Really, to do OIT well, you really need to make sure that you are below a kiddo's reaction threshold and kiddos are different, like their immune systems. They're different from each other. There are a lot of kids yes, absolutely. There are a lot of kids that can tolerate Palforzia, that can do the, or an equivalent protocol using peanut butter, or even different allergens using that sort of start with three milligrams, go to six, go to 12, go to 20, go to 40, go to 80. A lot of kids can tolerate that. Some kiddos you might need to stretch out the up doses. So instead of dosing every two weeks, you do every four weeks, really giving their immune system time to grow tolerance to it. But yeah, a lot of kiddos can really tolerate that, but some can't. So OIT really does have its drawbacks.

Dr. Alice Hoyt:

Is Xolair better? Well, Xolair has its drawbacks too. Right, it's a shot. It's a shot every two to four weeks, depending on a kiddo's total IgE level, not their allergen specific level, but it's kiddo's total IgE level, not their allergen specific level, but it's based on their total IgE level and it's based on their weight. And then when you stop Zolair, the IgE goes right back onto the allergy cells. Now stage three, meaning the allergy comes back.

Dr. Alice Hoyt:

Neither Xolair nor oral immunotherapy should be or are considered a cure. Neither of these are considered a cure for food allergy. That is because a cure is something that say you have a condition, you apply the cure to it, the condition goes away. You stop the cure, right, you stop the medication or whatever it is, and the condition does not return. Well, we know that with Xolair. When you stop the Xolair, the condition returns. Now stage three of OUtMATCH is looking at that and stage three, some of the data was presented and it showed that some kiddos were able to free eat their allergens after being on Xolair.

Dr. Alice Hoyt:

But in a lot of kiddos that tolerance kind of waned over time, meaning kids started reacting to foods that they had been tolerating while they had some Xolair in their system is how we're interpreting that, but not all kids right. So also with Xolair, I come back to it's a shot, it's a shot. And so do you want to be taking a shot? And look, shots are what they are. People give themselves shots all the time. But do you want to be committed to taking a medicine every two to four weeks?

Dr. Alice Hoyt:

If you could be committed to the alternative well, one of the alternatives of oral immunotherapy of making sure you eat the food regularly. Once you get to food freedom or whatever it is we want to call it and many kids can get to that point with oral immunotherapy evidence-based oral immunotherapy performed with a good OIT board-certified allergist you can get to that point of getting the food into the diet safely. So OIT is not a cure, though, because if you stop the food, if you get to tolerating, say, you're able to eat. You used to be allergic to peanut and now you can eat peanut butter and jelly sandwiches, as much of peanut butter as you want, whenever you want, because you went through an oral immunotherapy process. You, over time, were desensitized again under the strict supervision of an allergist who knows what they're doing. Then let's say you stop that for like six months, 12 months, and you strictly avoid all things peanut. Well, we know, based on studies, that that sustained unresponsiveness, meaning that tolerance you built to peanut. If you don't continue to expose your body to the allergen, then you can lose that tolerance. So it too OIT too is not considered a cure.

Dr. Alice Hoyt:

Overall, the whole point of this podcast episode was to address the claim that Xolair is superior to multifood OIT, and I very strongly stand behind one. The study did not demonstrate that because the OIT protocol is not consistent with most OIT protocols utilized in research studies and also in clinical practice. But two, it all comes back to the patient and what is best for the patient. It all comes back to the patient and what is best for the patient. And OIT might be superior to Xolair for one patient, but Xolair might be superior to OIT to another patient. So that all comes back to shared decision making between you, your child and your child's allergist. And that is how you decide what is superior.

Dr. Alice Hoyt:

Yes, applying all of this evidence and information and research and studies. Yes, absolutely, but just remember it is not one size fits all. One treatment that's great for one kiddo might not necessarily be the right treatment for another kiddo, and all kiddos and families should have personalized, shared decision-making to help inform what is the best option for your kiddo. That's the episode. Thanks so much for tuning in. Of course I'm an allergist, but I'm not your allergist. So talk with your allergist about what you learned on this episode and visit us at foodallergyandyourkiddocom where you can submit your family's questions. God bless you and God bless your family.