March 19, 2025 • 32 mins
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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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Episode Transcript
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Dr. Alice Hoyt (00:01):
Is Xolair (omalizumab) really superior to
oral immunotherapy when it comesto treating patients with
multiple food allergies?
That is exactly what I'm goingto discuss with you today on
food allergy and your kiddo.
Okay, so you may have seen aheadline recently.
(00:22):
One on the NIH's website saysomalizumab treats multi-food
allergy better than oralimmunotherapy.
High rate of oral immunotherapyside effects in NIH trial
explains superiority ofomalizumab.
That's one of the headlines.
Another headline that was onthe American Academy of Allergy,
(00:45):
asthma and Immunology's website, of which I am a fellow of the
Quad AI, as it's called.
That headline read Omelizumabis superior to oral
immunotherapy in multi-foodallergy treatment study.
So what is really going on here?
What is Omelizumab?
The brand name is XolairX-O-L-A-I-R.
(01:09):
The brand name is Xolair.
What is that?
And what is really multi-foodoral immunotherapy or OIT, and
is one truly better than theother?
I recently wrote about this onthe Food Allergy Pediatric Hub,
which is a food allergy focusedclinician pediatrician website
(01:34):
where I try to provideevidence-based information, of
course, to my colleagues whoserve families who have food
allergies, treat kiddos who havefood allergies, but are not
they themselves allergists?
So general practitioners,really any clinician who wants
to know more about what's goingon in the world of food
(01:56):
allergies, but they themselvesare 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 writeabout my experience at the
academy meeting, the quad AImeeting that I attended recently
, where this information waspresented.
So this is the topic that Iselected because hello, when you
(02:20):
hear a headline like that thatone treatment approach is
superior to another treatmentapproach 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 toanother for everybody, right?
(02:51):
I mean, in 99.999% of cases, ofall things medicine, we need to
personalize the approach, andone treatment option for one
kiddo is not going to besuperior to a different
treatment option for anotherkiddo.
So, but why?
Why was this, in my opinion,very strong claim made and do
(03:14):
they have the data to reallyback up such a large claim?
I do not think they do and I'mgoing to tell you why, and full
disclosure I prescribe Xolair.
I also do multi-food oralimmunotherapy.
I do it all.
I'm really happy that we haveall these options now to really
(03:34):
try to serve families the bestway we can in the best approach
for their kiddo.
So what does that really meanwith all this?
First let's talk about what isXolair or omalizumab.
Xolair is a biologic medicationthat is injected once or twice
(03:56):
a month to help prevent a kiddoor adult who has a food allergy
from having a severe allergicreaction should they ingest
their allergen.
So what Xolair is is anantibody that actually binds to
the allergic antibody.
Allergic antibodies are calledIgE, immunoglobulin E.
(04:18):
I call them allergic antibodies.
They're not just allergicantibodies, they do other
important things.
But for whatever reason, in thelast few hundred years we as
humans have started makingallergic antibodies or IgE,
specific to foods like peanut,like cashew, like milk, and in
(04:40):
these last few hundred yearswe've had the onset of allergic
conditions.
I'll put a link to one of myfavorite papers by Dr Thomas
Platts Mills, who was one of mymentors at the University of
Virginia Wahoo Wah, where Icompleted a three-year allergy
(05:01):
fellowship.
Dr Platts- Mills is agrandfather of allergy and he
wrotea beautiful paper a fewyears ago, really discussing the
onset of allergic conditions.
If you were to come see me inmy office I would probably use a
line along the lines of Job hada lot of bad things, but he
(05:21):
didn't have food allergies.
That's because really allergiesdid not come on the scene until
just a couple hundred years ago, and food allergy in particular
.
The uptick in food allergy wasfirst noted in the 1990s, and
really just in the 1900s waswhen we really started even
seeing this thing calledanaphylaxis to foods.
(05:43):
So why we as humans havestarted making IgE to foods, we
really don't know.
But here we are.
We are in a place where we makeIgE to foods and kids now can
have food allergies.
Five to 10% of kids, dependingon the study you read, have an
(06:04):
anaphylactic food allergy.
So what's really going on withthat and how can we treat it?
Well, that comes back to thewhole topic of today.
Right, like, what about Xolair?
What about OIT?
Is one better than the other?
Back to what Xolair is.
Xolair is an antibody that'sgoing to bind to the allergic
antibodies, whether it's peanut,cashew, whatever it is.
(06:26):
It's going to bind to all thoseallergic antibodies that are
floating around in a person'sbloodstream and it's going to
allow the immune system to sortof dispose of those antibodies
so that they are no longer ableto really hang out on allergy
cells.
And if those allergicantibodies are not hanging out
on your allergy cells then it'sreally hard to activate those
(06:46):
allergy cells because it's thoseallergic antibodies that bind
to the allergen and then triggerthat allergy cell to then
activate.
So you can see an example akiddo who has a peanut allergy.
They have peanut specific IgEor peanut allergic antibodies
hanging out on their allergycells, their mast cells and
(07:08):
their basophils when they eatpeanut.
Peanut protein binds to theallergic antibody that's hanging
out on the allergy cell andthat binding ultimately triggers
that allergy cell to becomeactivated, specifically to
degranulate the granules withinthat cell get kind of spewed out
(07:30):
the contents of those granules,which is histamine,
vasodilators vaso meaning vessel, dilate, meaning open up.
That's why kiddos and adultswho have anomaloxis can have a
drop in blood pressure.
It's because of what's in thegranules of the allergy cells,
also bronchoconstrictors broncomeaning our airways constrict,
(07:50):
meaning get smallerBronchoconstrictors are in the
granules.
So when those allergy cells getactivated that's how an
anaphylactic reaction can occuris because the contents of the
granules is being spewed outlocally into the tissues, into
circulation, and the treatmentfor that is epinephrine.
(08:10):
Epinephrine binds to theallergy cell, stabilizes it,
tells it hey, stop having thisterrible reaction.
Also binds to the blood vessels, tells them to tighten up so
that we can combat any drop inblood pressure, we can combat
swelling, we can combat thehistamine effect, all the things
.
So epinephrine is yourtreatment for anaphylaxis.
(08:33):
Xolair binds those allergicantibodies, kind of takes them
out of circulation.
So then if you don't have theallergic antibodies on the
allergy cell anymore and youaccidentally eat a peanut, well,
that peanut doesn't have a wayto trigger the allergy cell.
Amazing, amazing, that isamazing.
That is amazing because ithaving Zolair approved to
(08:57):
prevent anaphylaxis when itcomes to kiddos and adults with
food allergies, it now providesmany families an amazing safety
net so that if their child wereto accidentally ingest their
allergen, then they won't have asevere allergic reaction.
It is amazing.
Xolair itself is not a new drug.
(09:17):
It was approved last year bythe FDA as a management tool as
a treatment of food allergy bypreventing anaphylaxis from
accidental ingestions.
But Zoller itself.
(09:38):
We as allergists have beenusing Xolair for 20 years.
It helps people who have asthma, it helps people who have
chronic hives, it helps peoplewho have nasal polyps, allergic
rhinitis, because it's theanti-IgE, it's the anti-allergic
antibody, so it helps lots ofallergic conditions.
It's really fantastic.
(09:58):
So, as you can see, like I'mnot an anti-zolair person, I
think zolair is great.
There was a generic recentlymade available or a biosimilar
that we'll talk about on adifferent episode.
Made available Like this isgood.
It is good to have this option,but it comes back to is this
(10:18):
option better than oralimmunotherapy and why is this
study called the OUtMATCH Study?
Why is this study saying thatit is better?
Well, let's talk a little bitnow about what OIT is.
I've talked about OIT multipletimes on the podcast.
I've had amazing guests on thepodcast talking about OIT.
(10:38):
What OIT is, or oralimmunotherapy, is a treatment
plan for food allergyanaphylactic food allergy where
over time we give the kiddo orthe adult small amounts of their
allergen.
They take it every day and thenwe increase that every few
weeks until we get them to amaintenance dose.
(10:59):
Once they're on a maintenancedose so a maintenance dose of
peanut for a peanut allergymight be half a teaspoon of
peanut butter we keep them onthat, recheck their labs After 6
, 12 months, see if we've drivendown their allergic antibody
level and see also how well havethey been tolerating their dose
(11:19):
.
Do they like it?
Do they want to eat more of it?
Have they had accidentalingestions of eating a whole lot
more of it?
All the clinical indicators oftolerance, before we then say,
okay, well, let's do a full dosechallenge and see if you can
eat two or three tablespoons ofpeanut butter.
That is oral immunotherapy,where we introduce the allergen
(11:44):
in low amounts and slowlyincrease the amount over time,
teaching the body to tolerate afood.
Now that tolerance, while ithas something to do with IgE,
over time the IgE level will godown.
At first, actually, the IgElevel kind of pops up because
(12:05):
when a kid is being exposed totheir allergen, their immune
system is recognizing it andimmunoglobulin production will
initially increase.
But the way OIT works is byactually accessing a different
part of the immune system, apart of the immune system that
involves regulatory T cells, andI won't go down the stream of
(12:31):
an immune lecture right now.
But ultimately OIT is accessinga different compartment of the
immune system and it is growingtolerance to the food and that
development of tolerance overtime will overcome in most cases
.
Right, no treatment is 100% foreverybody, but in most cases
(12:54):
over time we're able to growtolerance to a food in amounts
that will make a kiddo at leastbite safe amounts that will make
a kiddo at least bite safe,meaning if they were to
accidentally eat a bite of apeanut butter cookie they
wouldn't have a severe allergicreaction, whereas before
starting the treatment, if theywere to accidentally take a bite
(13:14):
of a peanut butter cookie theycould have a severe reaction.
So OIT is going to buildtolerance to a food.
So OIT is going to buildtolerance to a food.
Now, is OIT a better treatmentthan omelizumab or Zolaire?
Well, let's talk about that.
In this study what was comparedwas omalizumab and a placebo
(13:43):
version of oral immunotherapy.
That was one treatment arm.
The other treatment arm wasplacebo, omalizumab or
placebozolair and a truemulti-food oral immunotherapy, a
true multi-food oralimmunotherapy.
(14:04):
Now, the issue with this and Iwill put a link in the show
notes to the visual that Icreated both for Doximity and
then also on the Food AllergyPediatric Hub article I
mentioned to you is that theoral immunotherapy protocol that
was used in Outmatch wasincredibly aggressive.
What do I mean by aggressive?
Well, I mentioned earlier whenI talked about how do you do OIT
(14:25):
, that OIT is low amounts of thealleralforzia protocol.
Palforzia is the FDA-approvedoral immunotherapy product that
(14:49):
treats peanut allergy.
It is defatted peanut flour.
The way Palforzia works is it'sthese little capsules of
pre-measured amounts of thedefatted peanut flour.
You open up the capsules andmix it into applesauce and
that's how you take your dose,or that's how you give your
kiddo your dose.
(15:09):
Now, the first day of doingPalforzia you do what's called
an escalation day, meaning yougo into the allergist office and
you start with 0.5 milligramsof the allergen, then you go up
to one milligram, so of peanutprotein, then 1.5, then three,
(15:32):
then six, and then you stop, andthe next day you go back and
then you start with just a threemilligram dose.
So a lot of allergists too, ifthey're using peanut butter or
non-Palforzia peanut powder, pb2powder, whatever the case may
be, they might start just bydoing three milligrams or they
(15:54):
might start by just giving adose of one milligram or two
milligrams.
So not doing that wholeescalation day, right?
Really, there's not a whole lotof evidence for that escalation
day anyway.
That's just how the protocolhas been done for a long time.
Palforzia is a very, very wellused studies, kind of like the
(16:15):
original sort of OIT protocol.
So they start with this littlemini 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 thenext two weeks, and that's three
milligrams.
And to put that intoperspective, one peanut has
about 300 milligrams of peanutprotein.
(16:36):
So basically, you're startingwith around three milligrams,
depending on what peanut productyou're using, or if you're
starting with around threemilligrams depending on what
peanut product you're using, orif you're using Palforzia, and
then you up dose every two weeks.
So the kiddo takes the doseevery day the same time every
day, one hour before and twohours after.
They can't be doing anythingthat's raising their heart rate
or raising their bodytemperature, because that can
(16:57):
lower the threshold to have anallergic reaction.
So, yes, it is a relativelyintense protocol, because if
you're a kiddo who runs track,who does sports, who does all
these things well, it can behard to find that pocket of time
where, an hour before and twohours after, you are awake and
(17:17):
you are not doing anythingthat's raising your heart rate
or raising your body temperature.
So that's why OIT is not theright fit for everybody.
That's why we talk about thingslike Solaire or sublingual
immunotherapy, which is a muchmore forgiving form of
immunotherapy.
So with Palforzia, with mostoral immunotherapies you updose
(17:40):
every two weeks.
So in the Palforzia protocolthree milligram dose, then two
weeks on that, then sixmilligrams, then 12 milligrams,
then 20, 40, 80, 120, 160, 200,240, up to 300.
And that's your maintenancedose.
So 11 updoses you.
You up dose every two weeks, nomore, no, no sooner than that.
(18:04):
But some families will stretchit out or some allergists will
stretch it out too, depending onhow well is the kiddo
tolerating it.
So you could see like it startspretty small and and and goes
up kind of doubles three to 6, 6to 12, and then 12 to 20, and
then 20 to 40.
And this is all every two weeks.
And then 40 to 80.
(18:24):
And then it goes up by 40 untilyou get to 240.
Then you make a little bitbigger of a jump to 300, and 300
is your maintenance dose.
So that's 11 up doses.
Let's look at the protocol thatOutmatch used as their OIT.
They started with threemilligrams of the allergen and
(18:45):
then went up to 30 and then wentup to 60, and then went up to
125 and then up to 250, 375, 560, 800, up to a thousand
milligrams at dose number nineto 1,000 milligrams at dose
number nine Now.
Leading up to this, all of thekids were on and it was all kids
(19:06):
in the study.
Now the kicker about this studyis that this part of the study
the Zolair versus OIT this isactually stage two of the study.
Stage one of the study is whatgot omelizumab or Zoller,
approved by the FDA to preventanaphylaxis from accidental
ingestion of a food allergen.
That was stage one of the study.
(19:26):
Stage one of the study comparedomelizumab to placebo.
Oit was not involved in stageone.
Stage one very clearlydemonstrated that omelizumab
does protect against severeallergic reactions when someone
eats their allergen.
They demonstrated this bychallenging kids first to make
(19:50):
sure that they were allergic tothe food, then enrolling the
kids and the kiddo either was onomalizumab or they were on
placebo for 16 to 20 weeks andthen they challenged them again
and the kids who were challengedon Xolair.
They were able to consume a lotmore of their food allergen
(20:12):
before having a reaction.
The kids who were not on Xolairyou didn't see that effect.
So Xolair was clearlyprotective.
Stage two of this study is wherethey took some of those kids
who were on Xolair or on placeboand then they put them all on
(20:34):
Xolair for eight weeks and Thenthey stratified the kids to
either start multifood OIT orplacebo OIT.
They all continued Xolair foranother eight weeks and then the
group that was on the multifoodOIT got switched over to
placebo Xolair.
The other group that was onplacebo OIT continued on Zolaire
(20:59):
.
They continued this for 44weeks and then they repeated the
food challenges and what wasdemonstrated was that the kids
who were on the real OIT andplacebo Xolair many of them did
(21:20):
not tolerate OIT.
Well, they were havingreactions.
Well, I'm not surprised theywere having reactions because I
come back to the OIT protocolthat was used in OUtMATCH is
significantly more aggressivethan Palforzia, significantly
more aggressive than other OITprotocols that are regularly
(21:44):
used.
As an allergist who does a lotof OIT, I will tell you that I
do not have a protocol that goesfrom 3mg to 30mg to 60mg to
125mg to 250mg, basicallygetting a kiddo up to eating a
peanut with just five up doses.
(22:05):
No way, Jose, because thesekiddos are allergic.
And look, when the primaryinvestigator was asked about
this at the academy meeting,that was the first question.
I was so glad somebody went upthere and asked about it,
because if not, I was going togo ask and that's never fun to
go up into these.
Well, some people like to go,and you know, ask the question
(22:28):
in front of the big old group.
I don't really like to do that.
I would much rather have themon the podcast.
That's a great idea.
I should have them on thepodcast.
But I digress Tangent.
But when he he was asked, whenthe primary investigator was
asked like, hey, don't you thinkthis protocol was a little bit
aggressive, the response wasthat well, they had been on
(22:50):
zolair so we thought that thekids would tolerate it.
Well, that that's kind of thepart of part of the study.
And there was not a study donethat demonstrated that kids can
be on Xolair leading up to OITand then better tolerate an
(23:12):
expedited OIT protocol.
So I would say that Xolair issuperior to an expedited OIT
protocol.
But I would not say that Xolairis superior to multi-food OIT,
because what they comparedXolair to in OUtMATCH Stage 3 is
(23:37):
not multi-food OIT.
It's like aggressive, superquick multi-food OIT.
And if they wanted to compareit to expedited OIT, well, they
should have first demonstratedthat using Xolair prior to OIT
allows an allergist, allows akiddo to tolerate expedited OIT.
(24:01):
But that was not previouslydemonstrated and that clearly
was not demonstrated here.
Because why the headline isomalizumab is superior to OIT is
because a lot of the kiddosdidn't tolerate the OIT.
They didn't tolerate it becauseit was so aggressive.
So it's really disappointingthat the study was done this way
(24:26):
because it really didn'tcompare it to multifood OIT.
It didn't compare Zoller tomultifood OIT.
The study compared Xolair to anaggressive multifood OIT.
But what's interesting too isthat the kiddos who did tolerate
that expedited approach soabout half of them the outcome
(24:51):
with Zolaire was kind ofequivalent.
So in the kiddos who toleratedthis expedited OIT they did
about the same as the kiddos whowere on Zolaire.
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.
(25:14):
As I mentioned, it's got itsdrawbacks right, like an hour
before, two hours after, notbeing able to do anything that
raises heart rate, raises bodytemperature, that can really
impact somebody's life.
Also, even with Palforzia, withthe protocol that I mentioned
(25:39):
in the Palforzia study, like 14%of those kids had anaphylaxis
to the OIT, like Palforziaitself is not necessarily like
an easy breezy OIT protocol.
Really, to do OIT well, youreally need to make sure that
(25:59):
you are below a kiddo's reactionthreshold and kiddos are
different, like their immunesystems.
They're different from eachother.
There are a lot of kids yes,absolutely.
There are a lot of kids thatcan tolerate Palforzia, that can
do the, or an equivalentprotocol using peanut butter, or
even different allergens usingthat sort of start with three
(26:22):
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 tostretch out the up doses.
So instead of dosing every twoweeks, you do every four weeks,
really giving their immunesystem time to grow tolerance to
it.
But yeah, a lot of kiddos canreally tolerate that, but some
(26:42):
can't.
So OIT really does have itsdrawbacks.
Is Xolair better?
Well, Xolair has its drawbackstoo.
Right, it's a shot.
It's a shot every two to fourweeks, depending on a kiddo's
total IgE level, not theirallergen specific level, but
it's kiddo's total IgE level,not their allergen specific
(27:04):
level, but it's based on theirtotal 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 theallergy comes back.
Neither Xolair nor oralimmunotherapy should be or are
(27:27):
considered a cure.
Neither of these are considereda cure for food allergy.
That is because a cure issomething that say you have a
condition, you apply the cure toit, the condition goes away.
You stop the cure, right, youstop the medication or whatever
it is, and the condition doesnot return.
Well, we know that with Xolair.
When you stop the Xolair, thecondition returns.
(27:51):
Now stage three of OUtMATCH islooking at that and stage three,
some of the data was presentedand it showed that some kiddos
were able to free eat theirallergens after being on Xolair.
But in a lot of kiddos thattolerance kind of waned over
time, meaning kids startedreacting to foods that they had
(28:14):
been tolerating while they hadsome Xolair in their system is
how we're interpreting that, butnot all kids right.
So also with Xolair, I comeback to it's a shot, it's a shot
.
And so do you want to be takinga shot?
(28:34):
And look, shots are what theyare.
People give themselves shotsall the time.
But do you want to be committedto taking a medicine every two
to four weeks?
If you could be committed to thealternative well, one of the
alternatives of oralimmunotherapy of making sure you
eat the food regularly.
Once you get to food freedom orwhatever it is we want to call
(28:57):
it and many kids can get to thatpoint with oral immunotherapy
evidence-based oralimmunotherapy performed with a
good OIT board-certifiedallergist you can get to that
point of getting the food intothe diet safely.
So OIT is not a cure, though,because if you stop the food, if
(29:20):
you get to tolerating, say,you're able to eat.
You used to be allergic topeanut and now you can eat
peanut butter and jellysandwiches, as much of peanut
butter as you want, whenever youwant, because you went through
an oral immunotherapy process.
You, over time, weredesensitized again under the
strict supervision of anallergist who knows what they're
doing.
Then let's say you stop thatfor like six months, 12 months,
(29:45):
and you strictly avoid allthings peanut.
Well, we know, based on studies, that that sustained
unresponsiveness, meaning thattolerance you built to peanut.
If you don't continue to exposeyour body to the allergen, then
you can lose that tolerance.
So it too OIT too is notconsidered a cure.
(30:08):
Overall, the whole point of thispodcast episode was to address
the claim that Xolair issuperior to multifood OIT, and I
very strongly stand behind one.
The study did not demonstratethat because the OIT protocol is
not consistent with most OITprotocols utilized in research
(30:31):
studies and also in clinicalpractice.
But two, it all comes back tothe patient and what is best for
the patient.
It all comes back to thepatient and what is best for the
patient.
And OIT might be superior toXolair for one patient, but
Xolair might be superior to OITto another patient.
So that all comes back toshared decision making between
(30:52):
you, your child and your child'sallergist.
And that is how you decide whatis superior.
Yes, applying all of thisevidence and information and
research and studies.
Yes, absolutely, but justremember it is not one size fits
all.
One treatment that's great forone kiddo might not necessarily
(31:15):
be the right treatment foranother kiddo, and all kiddos
and families should havepersonalized, shared
decision-making to help informwhat is the best option for your
kiddo.
That's the episode.
Thanks so much for tuning in.
(31:35):
Of course I'm an allergist, butI'm not your allergist.
So talk with your allergistabout what you learned on this
episode and visit us atfoodallergyandyourkiddocom where
you can submit your family'squestions.
God bless you and God blessyour family.
Is Xolair (omalizumab) really superior to
oral immunotherapy when it comesto treating patients with
multiple food allergies?
That is exactly what I'm goingto discuss with you today on
food allergy and your kiddo.
Okay, so you may have seen aheadline recently.
(00:22):
One on the NIH's website saysomalizumab treats multi-food
allergy better than oralimmunotherapy.
High rate of oral immunotherapyside effects in NIH trial
explains superiority ofomalizumab.
That's one of the headlines.
Another headline that was onthe American Academy of Allergy,
(00:45):
asthma and Immunology's website, of which I am a fellow of the
Quad AI, as it's called.
That headline read Omelizumabis superior to oral
immunotherapy in multi-foodallergy treatment study.
So what is really going on here?
What is Omelizumab?
The brand name is XolairX-O-L-A-I-R.
(01:09):
The brand name is Xolair.
What is that?
And what is really multi-foodoral immunotherapy or OIT, and
is one truly better than theother?
I recently wrote about this onthe Food Allergy Pediatric Hub,
which is a food allergy focusedclinician pediatrician website
(01:34):
where I try to provideevidence-based information, of
course, to my colleagues whoserve families who have food
allergies, treat kiddos who havefood allergies, but are not
they themselves allergists?
So general practitioners,really any clinician who wants
to know more about what's goingon in the world of food
(01:56):
allergies, but they themselvesare 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 writeabout my experience at the
academy meeting, the quad AImeeting that I attended recently
, where this information waspresented.
So this is the topic that Iselected because hello, when you
(02:20):
hear a headline like that thatone treatment approach is
superior to another treatmentapproach 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 toanother for everybody, right?
(02:51):
I mean, in 99.999% of cases, ofall things medicine, we need to
personalize the approach, andone treatment option for one
kiddo is not going to besuperior to a different
treatment option for anotherkiddo.
So, but why?
Why was this, in my opinion,very strong claim made and do
(03:14):
they have the data to reallyback up such a large claim?
I do not think they do and I'mgoing to tell you why, and full
disclosure I prescribe Xolair.
I also do multi-food oralimmunotherapy.
I do it all.
I'm really happy that we haveall these options now to really
(03:34):
try to serve families the bestway we can in the best approach
for their kiddo.
So what does that really meanwith all this?
First let's talk about what isXolair or omalizumab.
Xolair is a biologic medicationthat is injected once or twice
(03:56):
a month to help prevent a kiddoor adult who has a food allergy
from having a severe allergicreaction should they ingest
their allergen.
So what Xolair is is anantibody that actually binds to
the allergic antibody.
Allergic antibodies are calledIgE, immunoglobulin E.
(04:18):
I call them allergic antibodies.
They're not just allergicantibodies, they do other
important things.
But for whatever reason, in thelast few hundred years we as
humans have started makingallergic antibodies or IgE,
specific to foods like peanut,like cashew, like milk, and in
(04:40):
these last few hundred yearswe've had the onset of allergic
conditions.
I'll put a link to one of myfavorite papers by Dr Thomas
Platts Mills, who was one of mymentors at the University of
Virginia Wahoo Wah, where Icompleted a three-year allergy
(05:01):
fellowship.
Dr Platts- Mills is agrandfather of allergy and he
wrotea beautiful paper a fewyears ago, really discussing the
onset of allergic conditions.
If you were to come see me inmy office I would probably use a
line along the lines of Job hada lot of bad things, but he
(05:21):
didn't have food allergies.
That's because really allergiesdid not come on the scene until
just a couple hundred years ago, and food allergy in particular
.
The uptick in food allergy wasfirst noted in the 1990s, and
really just in the 1900s waswhen we really started even
seeing this thing calledanaphylaxis to foods.
(05:43):
So why we as humans havestarted making IgE to foods, we
really don't know.
But here we are.
We are in a place where we makeIgE to foods and kids now can
have food allergies.
Five to 10% of kids, dependingon the study you read, have an
(06:04):
anaphylactic food allergy.
So what's really going on withthat and how can we treat it?
Well, that comes back to thewhole topic of today.
Right, like, what about Xolair?
What about OIT?
Is one better than the other?
Back to what Xolair is.
Xolair is an antibody that'sgoing to bind to the allergic
antibodies, whether it's peanut,cashew, whatever it is.
(06:26):
It's going to bind to all thoseallergic antibodies that are
floating around in a person'sbloodstream and it's going to
allow the immune system to sortof dispose of those antibodies
so that they are no longer ableto really hang out on allergy
cells.
And if those allergicantibodies are not hanging out
on your allergy cells then it'sreally hard to activate those
(06:46):
allergy cells because it's thoseallergic antibodies that bind
to the allergen and then triggerthat allergy cell to then
activate.
So you can see an example akiddo who has a peanut allergy.
They have peanut specific IgEor peanut allergic antibodies
hanging out on their allergycells, their mast cells and
(07:08):
their basophils when they eatpeanut.
Peanut protein binds to theallergic antibody that's hanging
out on the allergy cell andthat binding ultimately triggers
that allergy cell to becomeactivated, specifically to
degranulate the granules withinthat cell get kind of spewed out
(07:30):
the contents of those granules,which is histamine,
vasodilators vaso meaning vessel, dilate, meaning open up.
That's why kiddos and adultswho have anomaloxis can have a
drop in blood pressure.
It's because of what's in thegranules of the allergy cells,
also bronchoconstrictors broncomeaning our airways constrict,
(07:50):
meaning get smallerBronchoconstrictors are in the
granules.
So when those allergy cells getactivated that's how an
anaphylactic reaction can occuris because the contents of the
granules is being spewed outlocally into the tissues, into
circulation, and the treatmentfor that is epinephrine.
(08:10):
Epinephrine binds to theallergy cell, stabilizes it,
tells it hey, stop having thisterrible reaction.
Also binds to the blood vessels, tells them to tighten up so
that we can combat any drop inblood pressure, we can combat
swelling, we can combat thehistamine effect, all the things
.
So epinephrine is yourtreatment for anaphylaxis.
(08:33):
Xolair binds those allergicantibodies, kind of takes them
out of circulation.
So then if you don't have theallergic antibodies on the
allergy cell anymore and youaccidentally eat a peanut, well,
that peanut doesn't have a wayto trigger the allergy cell.
Amazing, amazing, that isamazing.
That is amazing because ithaving Zolair approved to
(08:57):
prevent anaphylaxis when itcomes to kiddos and adults with
food allergies, it now providesmany families an amazing safety
net so that if their child wereto accidentally ingest their
allergen, then they won't have asevere allergic reaction.
It is amazing.
Xolair itself is not a new drug.
(09:17):
It was approved last year bythe FDA as a management tool as
a treatment of food allergy bypreventing anaphylaxis from
accidental ingestions.
But Zoller itself.
(09:38):
We as allergists have beenusing Xolair for 20 years.
It helps people who have asthma, it helps people who have
chronic hives, it helps peoplewho have nasal polyps, allergic
rhinitis, because it's theanti-IgE, it's the anti-allergic
antibody, so it helps lots ofallergic conditions.
It's really fantastic.
(09:58):
So, as you can see, like I'mnot an anti-zolair person, I
think zolair is great.
There was a generic recentlymade available or a biosimilar
that we'll talk about on adifferent episode.
Made available Like this isgood.
It is good to have this option,but it comes back to is this
(10:18):
option better than oralimmunotherapy and why is this
study called the OUtMATCH Study?
Why is this study saying thatit is better?
Well, let's talk a little bitnow about what OIT is.
I've talked about OIT multipletimes on the podcast.
I've had amazing guests on thepodcast talking about OIT.
(10:38):
What OIT is, or oralimmunotherapy, is a treatment
plan for food allergyanaphylactic food allergy where
over time we give the kiddo orthe adult small amounts of their
allergen.
They take it every day and thenwe increase that every few
weeks until we get them to amaintenance dose.
(10:59):
Once they're on a maintenancedose so a maintenance dose of
peanut for a peanut allergymight be half a teaspoon of
peanut butter we keep them onthat, recheck their labs After 6
, 12 months, see if we've drivendown their allergic antibody
level and see also how well havethey been tolerating their dose
(11:19):
.
Do they like it?
Do they want to eat more of it?
Have they had accidentalingestions of eating a whole lot
more of it?
All the clinical indicators oftolerance, before we then say,
okay, well, let's do a full dosechallenge and see if you can
eat two or three tablespoons ofpeanut butter.
That is oral immunotherapy,where we introduce the allergen
(11:44):
in low amounts and slowlyincrease the amount over time,
teaching the body to tolerate afood.
Now that tolerance, while ithas something to do with IgE,
over time the IgE level will godown.
At first, actually, the IgElevel kind of pops up because
(12:05):
when a kid is being exposed totheir allergen, their immune
system is recognizing it andimmunoglobulin production will
initially increase.
But the way OIT works is byactually accessing a different
part of the immune system, apart of the immune system that
involves regulatory T cells, andI won't go down the stream of
(12:31):
an immune lecture right now.
But ultimately OIT is accessinga different compartment of the
immune system and it is growingtolerance to the food and that
development of tolerance overtime will overcome in most cases
.
Right, no treatment is 100% foreverybody, but in most cases
(12:54):
over time we're able to growtolerance to a food in amounts
that will make a kiddo at leastbite safe amounts that will make
a kiddo at least bite safe,meaning if they were to
accidentally eat a bite of apeanut butter cookie they
wouldn't have a severe allergicreaction, whereas before
starting the treatment, if theywere to accidentally take a bite
(13:14):
of a peanut butter cookie theycould have a severe reaction.
So OIT is going to buildtolerance to a food.
So OIT is going to buildtolerance to a food.
Now, is OIT a better treatmentthan omelizumab or Zolaire?
Well, let's talk about that.
In this study what was comparedwas omalizumab and a placebo
(13:43):
version of oral immunotherapy.
That was one treatment arm.
The other treatment arm wasplacebo, omalizumab or
placebozolair and a truemulti-food oral immunotherapy, a
true multi-food oralimmunotherapy.
(14:04):
Now, the issue with this and Iwill put a link in the show
notes to the visual that Icreated both for Doximity and
then also on the Food AllergyPediatric Hub article I
mentioned to you is that theoral immunotherapy protocol that
was used in Outmatch wasincredibly aggressive.
What do I mean by aggressive?
Well, I mentioned earlier whenI talked about how do you do OIT
(14:25):
, that OIT is low amounts of thealleralforzia protocol.
Palforzia is the FDA-approvedoral immunotherapy product that
(14:49):
treats peanut allergy.
It is defatted peanut flour.
The way Palforzia works is it'sthese little capsules of
pre-measured amounts of thedefatted peanut flour.
You open up the capsules andmix it into applesauce and
that's how you take your dose,or that's how you give your
kiddo your dose.
(15:09):
Now, the first day of doingPalforzia you do what's called
an escalation day, meaning yougo into the allergist office and
you start with 0.5 milligramsof the allergen, then you go up
to one milligram, so of peanutprotein, then 1.5, then three,
(15:32):
then six, and then you stop, andthe next day you go back and
then you start with just a threemilligram dose.
So a lot of allergists too, ifthey're using peanut butter or
non-Palforzia peanut powder, pb2powder, whatever the case may
be, they might start just bydoing three milligrams or they
(15:54):
might start by just giving adose of one milligram or two
milligrams.
So not doing that wholeescalation day, right?
Really, there's not a whole lotof evidence for that escalation
day anyway.
That's just how the protocolhas been done for a long time.
Palforzia is a very, very wellused studies, kind of like the
(16:15):
original sort of OIT protocol.
So they start with this littlemini 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 thenext two weeks, and that's three
milligrams.
And to put that intoperspective, one peanut has
about 300 milligrams of peanutprotein.
(16:36):
So basically, you're startingwith around three milligrams,
depending on what peanut productyou're using, or if you're
starting with around threemilligrams depending on what
peanut product you're using, orif you're using Palforzia, and
then you up dose every two weeks.
So the kiddo takes the doseevery day the same time every
day, one hour before and twohours after.
They can't be doing anythingthat's raising their heart rate
or raising their bodytemperature, because that can
(16:57):
lower the threshold to have anallergic reaction.
So, yes, it is a relativelyintense protocol, because if
you're a kiddo who runs track,who does sports, who does all
these things well, it can behard to find that pocket of time
where, an hour before and twohours after, you are awake and
(17:17):
you are not doing anythingthat's raising your heart rate
or raising your body temperature.
So that's why OIT is not theright fit for everybody.
That's why we talk about thingslike Solaire or sublingual
immunotherapy, which is a muchmore forgiving form of
immunotherapy.
So with Palforzia, with mostoral immunotherapies you updose
(17:40):
every two weeks.
So in the Palforzia protocolthree milligram dose, then two
weeks on that, then sixmilligrams, then 12 milligrams,
then 20, 40, 80, 120, 160, 200,240, up to 300.
And that's your maintenancedose.
So 11 updoses you.
You up dose every two weeks, nomore, no, no sooner than that.
(18:04):
But some families will stretchit out or some allergists will
stretch it out too, depending onhow well is the kiddo
tolerating it.
So you could see like it startspretty small and and and goes
up kind of doubles three to 6, 6to 12, and then 12 to 20, and
then 20 to 40.
And this is all every two weeks.
And then 40 to 80.
(18:24):
And then it goes up by 40 untilyou get to 240.
Then you make a little bitbigger of a jump to 300, and 300
is your maintenance dose.
So that's 11 up doses.
Let's look at the protocol thatOutmatch used as their OIT.
They started with threemilligrams of the allergen and
(18:45):
then went up to 30 and then wentup to 60, and then went up to
125 and then up to 250, 375, 560, 800, up to a thousand
milligrams at dose number nineto 1,000 milligrams at dose
number nine Now.
Leading up to this, all of thekids were on and it was all kids
(19:06):
in the study.
Now the kicker about this studyis that this part of the study
the Zolair versus OIT this isactually stage two of the study.
Stage one of the study is whatgot omelizumab or Zoller,
approved by the FDA to preventanaphylaxis from accidental
ingestion of a food allergen.
That was stage one of the study.
(19:26):
Stage one of the study comparedomelizumab to placebo.
Oit was not involved in stageone.
Stage one very clearlydemonstrated that omelizumab
does protect against severeallergic reactions when someone
eats their allergen.
They demonstrated this bychallenging kids first to make
(19:50):
sure that they were allergic tothe food, then enrolling the
kids and the kiddo either was onomalizumab or they were on
placebo for 16 to 20 weeks andthen they challenged them again
and the kids who were challengedon Xolair.
They were able to consume a lotmore of their food allergen
(20:12):
before having a reaction.
The kids who were not on Xolairyou didn't see that effect.
So Xolair was clearlyprotective.
Stage two of this study is wherethey took some of those kids
who were on Xolair or on placeboand then they put them all on
(20:34):
Xolair for eight weeks and Thenthey stratified the kids to
either start multifood OIT orplacebo OIT.
They all continued Xolair foranother eight weeks and then the
group that was on the multifoodOIT got switched over to
placebo Xolair.
The other group that was onplacebo OIT continued on Zolaire
(20:59):
.
They continued this for 44weeks and then they repeated the
food challenges and what wasdemonstrated was that the kids
who were on the real OIT andplacebo Xolair many of them did
(21:20):
not tolerate OIT.
Well, they were havingreactions.
Well, I'm not surprised theywere having reactions because I
come back to the OIT protocolthat was used in OUtMATCH is
significantly more aggressivethan Palforzia, significantly
more aggressive than other OITprotocols that are regularly
(21:44):
used.
As an allergist who does a lotof OIT, I will tell you that I
do not have a protocol that goesfrom 3mg to 30mg to 60mg to
125mg to 250mg, basicallygetting a kiddo up to eating a
peanut with just five up doses.
(22:05):
No way, Jose, because thesekiddos are allergic.
And look, when the primaryinvestigator was asked about
this at the academy meeting,that was the first question.
I was so glad somebody went upthere and asked about it,
because if not, I was going togo ask and that's never fun to
go up into these.
Well, some people like to go,and you know, ask the question
(22:28):
in front of the big old group.
I don't really like to do that.
I would much rather have themon the podcast.
That's a great idea.
I should have them on thepodcast.
But I digress Tangent.
But when he he was asked, whenthe primary investigator was
asked like, hey, don't you thinkthis protocol was a little bit
aggressive, the response wasthat well, they had been on
(22:50):
zolair so we thought that thekids would tolerate it.
Well, that that's kind of thepart of part of the study.
And there was not a study donethat demonstrated that kids can
be on Xolair leading up to OITand then better tolerate an
(23:12):
expedited OIT protocol.
So I would say that Xolair issuperior to an expedited OIT
protocol.
But I would not say that Xolairis superior to multi-food OIT,
because what they comparedXolair to in OUtMATCH Stage 3 is
(23:37):
not multi-food OIT.
It's like aggressive, superquick multi-food OIT.
And if they wanted to compareit to expedited OIT, well, they
should have first demonstratedthat using Xolair prior to OIT
allows an allergist, allows akiddo to tolerate expedited OIT.
(24:01):
But that was not previouslydemonstrated and that clearly
was not demonstrated here.
Because why the headline isomalizumab is superior to OIT is
because a lot of the kiddosdidn't tolerate the OIT.
They didn't tolerate it becauseit was so aggressive.
So it's really disappointingthat the study was done this way
(24:26):
because it really didn'tcompare it to multifood OIT.
It didn't compare Zoller tomultifood OIT.
The study compared Xolair to anaggressive multifood OIT.
But what's interesting too isthat the kiddos who did tolerate
that expedited approach soabout half of them the outcome
(24:51):
with Zolaire was kind ofequivalent.
So in the kiddos who toleratedthis expedited OIT they did
about the same as the kiddos whowere on Zolaire.
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.
(25:14):
As I mentioned, it's got itsdrawbacks right, like an hour
before, two hours after, notbeing able to do anything that
raises heart rate, raises bodytemperature, that can really
impact somebody's life.
Also, even with Palforzia, withthe protocol that I mentioned
(25:39):
in the Palforzia study, like 14%of those kids had anaphylaxis
to the OIT, like Palforziaitself is not necessarily like
an easy breezy OIT protocol.
Really, to do OIT well, youreally need to make sure that
(25:59):
you are below a kiddo's reactionthreshold and kiddos are
different, like their immunesystems.
They're different from eachother.
There are a lot of kids yes,absolutely.
There are a lot of kids thatcan tolerate Palforzia, that can
do the, or an equivalentprotocol using peanut butter, or
even different allergens usingthat sort of start with three
(26:22):
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 tostretch out the up doses.
So instead of dosing every twoweeks, you do every four weeks,
really giving their immunesystem time to grow tolerance to
it.
But yeah, a lot of kiddos canreally tolerate that, but some
(26:42):
can't.
So OIT really does have itsdrawbacks.
Is Xolair better?
Well, Xolair has its drawbackstoo.
Right, it's a shot.
It's a shot every two to fourweeks, depending on a kiddo's
total IgE level, not theirallergen specific level, but
it's kiddo's total IgE level,not their allergen specific
(27:04):
level, but it's based on theirtotal 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 theallergy comes back.
Neither Xolair nor oralimmunotherapy should be or are
(27:27):
considered a cure.
Neither of these are considereda cure for food allergy.
That is because a cure issomething that say you have a
condition, you apply the cure toit, the condition goes away.
You stop the cure, right, youstop the medication or whatever
it is, and the condition doesnot return.
Well, we know that with Xolair.
When you stop the Xolair, thecondition returns.
(27:51):
Now stage three of OUtMATCH islooking at that and stage three,
some of the data was presentedand it showed that some kiddos
were able to free eat theirallergens after being on Xolair.
But in a lot of kiddos thattolerance kind of waned over
time, meaning kids startedreacting to foods that they had
(28:14):
been tolerating while they hadsome Xolair in their system is
how we're interpreting that, butnot all kids right.
So also with Xolair, I comeback to it's a shot, it's a shot
.
And so do you want to be takinga shot?
(28:34):
And look, shots are what theyare.
People give themselves shotsall the time.
But do you want to be committedto taking a medicine every two
to four weeks?
If you could be committed to thealternative well, one of the
alternatives of oralimmunotherapy of making sure you
eat the food regularly.
Once you get to food freedom orwhatever it is we want to call
(28:57):
it and many kids can get to thatpoint with oral immunotherapy
evidence-based oralimmunotherapy performed with a
good OIT board-certifiedallergist you can get to that
point of getting the food intothe diet safely.
So OIT is not a cure, though,because if you stop the food, if
(29:20):
you get to tolerating, say,you're able to eat.
You used to be allergic topeanut and now you can eat
peanut butter and jellysandwiches, as much of peanut
butter as you want, whenever youwant, because you went through
an oral immunotherapy process.
You, over time, weredesensitized again under the
strict supervision of anallergist who knows what they're
doing.
Then let's say you stop thatfor like six months, 12 months,
(29:45):
and you strictly avoid allthings peanut.
Well, we know, based on studies, that that sustained
unresponsiveness, meaning thattolerance you built to peanut.
If you don't continue to exposeyour body to the allergen, then
you can lose that tolerance.
So it too OIT too is notconsidered a cure.
(30:08):
Overall, the whole point of thispodcast episode was to address
the claim that Xolair issuperior to multifood OIT, and I
very strongly stand behind one.
The study did not demonstratethat because the OIT protocol is
not consistent with most OITprotocols utilized in research
(30:31):
studies and also in clinicalpractice.
But two, it all comes back tothe patient and what is best for
the patient.
It all comes back to thepatient and what is best for the
patient.
And OIT might be superior toXolair for one patient, but
Xolair might be superior to OITto another patient.
So that all comes back toshared decision making between
(30:52):
you, your child and your child'sallergist.
And that is how you decide whatis superior.
Yes, applying all of thisevidence and information and
research and studies.
Yes, absolutely, but justremember it is not one size fits
all.
One treatment that's great forone kiddo might not necessarily
(31:15):
be the right treatment foranother kiddo, and all kiddos
and families should havepersonalized, shared
decision-making to help informwhat is the best option for your
kiddo.
That's the episode.
Thanks so much for tuning in.
(31:35):
Of course I'm an allergist, butI'm not your allergist.
So talk with your allergistabout what you learned on this
episode and visit us atfoodallergyandyourkiddocom where
you can submit your family'squestions.
God bless you and God blessyour family.
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