This webinar was recorded on May 2, 2024
Approximately 20 million Americans have food allergies according to 2021 data from the CDC. Individualized management of food allergies is important because symptoms of food allergies can vary from person to person and reaction to reaction. In this webinar, learn about the current approaches of food allergy management.
Speaker:
- Aikaterini Anagnostou, MD (Hons) MSc PhD
Dr Anagnostou is Professor of Pediatrics at Texas Childrenโs Hospital and Baylor College of Medicine in Houston, Texas. She currently serves as Director of the Food Immunotherapy Program and Co-Director of the Food Allergy Program. She is also Lead for the Adolescent Transition Program for Allergy.ย Dr Anagnostou is passionate about investigating new and innovative therapies for food allergy. She is the PI for phase 3 trials of food allergy therapy and is also leading research projects on food allergy prevention, anaphylaxis, the microbiome and shared decision-making.ย She currently serves as the Chair of the Adverse Reactions to Foods Committee at the AAAAI and as the Vice Chair of the Food Allergy Committee at the ACAAI. She is also a member of the Practice, Diagnostics and Therapeutics Committee and the Anaphylaxis Committee at the AAAAI.ย Dr Anagnostou obtained her PhD from Cambridge University in the United Kingdom and her dissertation focused on two research trials of Peanut Oral Immunotherapy in children. Her research work was published inย Theย Lancetย and received international recognition.
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Transcript:ย While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.
Catherine:ย We are still waiting for some people to join so we will be starting in a moment or so. Thank you for your patience. OK. Hello everyone. My name is Catherine Blackwell. Thank you for joining us today. I am the chief health equity officer for Allergy & Asthma Network. Welcome to this webinar this afternoon. We are in for a real treat today with Dr. Allergy & Asthma asked –Aikaterini Anagnostou today’s present or. We have a a few housekeeping items. All participants will be on mute for the webinar. We will record the webinar and posted on our website within a few days. You will be able to find all of the recorded webinars on her website at allergyasthmanetwork.org. Scroll to the bottom to find any webinars that may interest you. This will be for an hour and that includes time for questions. We will take the questions at the end of the webinar. You can put your questions and the Q&A at any time. That is located at the bottom of your screen. We will have somebody monitoring the chat if you have questions or need help. We will get to as many questions as we can before we conclude today’s webinar. This advanced webinar is a partnership with the American College of allergy asthma and immunology. ACAAI for short. They offer physicians and attendance credits. You can create a free ACAAI account and get attendance credits to the portal. All attendees will be offering a certificate of attendance and no continuing education credit is provided. A few days after the webinar to can receive an email with additional information and a link to download the certificate of attendance. We will also try to add the link o the certificate in the chat. Let’s get started. Today’s topic is food allergies, current approaches towards end of the largest — individualized management. 20 million Americans have food allergies. Individualized management is really important because, as you know, symptoms of food allergies can vary from person to person and reaction to reaction. In this webinar you will learn about the current approaches of food allergy management and the importance of shared decision-making with food allergy patients and their families. With all that said it is my great pleasure to introduce our speaker, Dr. Aikaterini Anagnostou. Dr. Anagnostou is professor of pediatrics at Texas Children’s Hospital at Baylor College of medicine in Houston, Texas. She currently serves as director of the food immunotherapy program and codirector of the food allergy program. She’s also lead for the adolescent transition program for allergy. Dr. Anagnostou is passionate about investigating new and end of eight of therapies for food allergy. She is the principal investigator. Her Phase 3 trials of therapy and is also a leading — is leading projects on prevention, anaphylaxis, the micro biome and shared decision-making. She currently serves as the chair of the adverse reactions to boost committee and as the vice chair of the food allergy committee at the ACAAI and a member of the practice, diagnostics and therapeutics committee and the anaphylaxis committee. She obtained her PhD from Cambridge University in the United Kingdom and her dissertation focused on two research trials in her research is published in the Lancet and received international recognition. Thank you for being here, Dr. Anagnostou. I will turn it over to you.
Dr. Anagnostou:ย Thank you very much. That is a kind introduction. It is my pleasure to be here and I would like to welcome everyone to this webinar. These are my active disclosures. The learning objectives for the day include a description of both traditional and novel approaches to managing food allergies. An excellent nation and discussion on food allergy treatment approaches using both immunotherapies and also Biologics. A discussion on the key components of shared decision-making and food allergy management. Very brief introduction because I’m sure this audience already knows a lot about food allergies. Based on prevalence studies we have, an estimated 8% of children and 10% of adults in the United States are reported to currently have at least one food allergy. We know that food pose a burden to both patients and their families, and that burden is multifaceted. They have to deal with a lot, both patients and their families. One of the most important parts of this burden I hear a lot in my clinic as well is fear and anxiety. Especially surrounding accidental exposures, potential for severe life-threatening reactions. This can significantly affect the quality of life. What has fascinated me is thatย although there are hundreds ofย food allergens, more than 90%ย of allergic reactions thatย patients encounter are causedย by actually just those nine topย food allergens.ย Which include milk, egg, soy,ย wheat, peanut, tree nuts,ย sesame, fish and shellfish.ย It’s important to point outย these food allergies have aย different natural progress inย life.ย Milk, egg, soy and wheat areย generally allergies to getย outgrown.ย People go out of them — growย out of them.ย Peanut, tree nuts, sesame, fishย and shellfish not as much.ย Today we are focusing on theย management of food allergy.ย What do we mean by traditionalย approach?ย This refers to the approachย that has been around for manyย decades which involves completeย avoidance of the food that isย the trigger of the foodย allergy.ย It is very much an acceptableย approach that is still validย today and forms one of manyย choices that food allergicย individuals have nowadays forย the management of food allergy.ย Together with the traditionalย approach we educate patients onย how to prevent future exposuresย to their allergenic trigger,ย how to recognize signs andย symptoms of an allergicย reaction, and how to treatย those allergic reactions whichย include education on the use ofย epinephrine injectors.ย I cannot stress enough if youย giveย — this is an important point.ย In addition to the traditionalย approach we know have novelย management approaches that haveย come about in the last five toย 10 years.ย These include various forms ofย food immunotherapy, includingย oral immunotherapy andย sublingual and biologics.ย I believe most people attendingย this webinar have probablyย already heard about the recentย FDA approval for the use of Oย malizumabย There are other therapeuticย approaches in the pipeline thatย are in phase one trial so weย will not be discussing thoseย today.ย Let’s start with food, andย therapy.ย — immunotherapy.
I would like to point out thatย food immunotherapy has actuallyย made it as part of variousย guidelines all around the worldย that refer to management ofย food allergens.ย This is the EAACI guideline.ย They brought information andย guidance on food immunotherapyย in 2018.ย According to the EAACIย guideline, it should beย considered from the age of 45ย years with symptoms ofย persistent IgE mediated foodย allergy to cows milk, egg, andย peanut with sensitization toย the triggering allergen. Theย guideline recognizes theย majority of children that areย allergic to milk and egg areย likely to develop toleranceย spontaneously to both of theseย food allergens.ย For these patients theyย recognize it is acceptable toย wait and see whether thereย allergy outgrows beforeย initiating food immunotherapy.ย I will discuss the point ofย little later.ย I will be focusing on thisย presentation for earlyย immunotherapy.ย These are more recentย guidelines coming from theย global allergy and asthmaย excellence network.ย They focus on food allergyย management and they recommendย offering peanut oralย immunotherapy and especiallyย supervision to selectedย children aged 4 and up withย clinically diagnosed severe IgEย mediated peanut allergy.ย They offer the same forย children again age four andย above for severe persistentย mediated hands echo cow milkย allergies.ย What is meant is for severe —ย a history of severe reactionsย but also this refers to theย burden of food allergy.ย It recognizes that certainย children and certain familiesย may have a more severe burdenย compared to others.ย Let’s look a little bit aboutย what data are out there toย support our use of oralย immunotherapy for food allergicย patients.ย Most people are familiar by theย study on the left.ย This is the Palisades studyย published in 2018.ย It is the largest unit oralย immunotherapy study that hasย been published to date.ย It is a multicenter study thatย enrolled children between theย ages of 4 to 17 years of ageย who were randomized to receiveย either oral immunotherapy toย peanut or placebo.ย The primary outcome of theย study was the percentage ofย participants able to tolerateย 600 Villa grants of peanutย protein — milligrams subpoenaย protein, equivalent to two toย three peanuts.ย After a year of therapy.ย The children would initially goย into a rush phase where theyย would get the dose increasedย pretty rapidly within a day.ย Then they would enter a slowerย up dosing phase, the buildupย phase, with the aim to reach aย top dose of 300 milligrams.ย Once that dose was reached theย buildup period what and in theย minutes period — maintenanceย period would start with theyย would take 300 milligrams forย six months to complete a wholeย year of therapy.ย At the end of the trial it wasย noted that 67% of children wereย able to tolerate a 600ย milligrams dose without anyย dose limiting symptoms comparedย to 4% and Nicholas Evo a –aย placebo arm that did notย receive immunotherapy.ย It’s important to rememberย their 600 milligrams dosesย double with the kids was takingย for maintenance, the 300ย milligrams dose.ย When you look at the far left,ย the 300 Miller Graham dose itย is clear the percentage is muchย higher.ย When you look to the right forย the 1000 milligrams dose, alsoย reported after your therapy,ย the percentage is just overย 50%.ย Just over half were also ableย to tolerate much higher doses,ย more than triple theirย maintenance at the end of aย year of therapy.ย I mentioned the study wasย focused on children.ย There were also adults in theย study.
The results were notย statistically significant atย the end.ย This is most likely because ofย the number of adults was quiteย small.ย We were not able to detect suchย a signal.ย Although adults generally andย practice do not seek therapiesย as much as children, I didn’tย see any reason why oralย immunotherapy would not beย appropriate for an adult asย well or in any way lessย effective.ย The study on the right is theย stop II trial.ย 100 peanut allergic childrenย who after six months of oralย immunotherapy were able toย tolerate five peanuts.ย 82% reached that dose.ย When they were challenged to aย much higher dose of theirย maintenance, 1400 milligrams ofย peanut protein, 62% were ableย to tolerate that higher dose asย well.ย Two different studies.ย One multicenter and one singleย center.ย Different parts of the world.ย As you can see, the results inย terms of efficacy are similar.ย The rate of treatment relatedย anaphylaxis reported for theย Palisades study was 14%.ย For the stop II trial, 1%.ย Moving on to real worldย studies, this was a study thatย recruited 145 peanut allergicย individuals within the ages ofย 4 to 18 years old.ย 77.9% were successfullyย desensitized to a total ofย three grams of peanut protein.ย Then they investigators wantedย to look at long-termย maintenance.ย They split the patients intoย two groups.ย One was the high mains group.ย They received three grams. Theย other was the low dose manusย group that received less thanย half of the initial maintenanceย dose.ย 1200 milligrams. Both groupsย were followed up for sixย months.ย It was found that when theyย were re-challenged to theย initial dose of 3000ย milligrams, 100% on theย high-dose armor successful,ย which we expect because theyย took that same dose duringย maintenance.ย Versus 95.5% in the low doseย maintenance arm.ย Adherence to treatment wasย quite different.ย It was found to beย significantly higher in thoseย patients that belonged to theย low maintenance group.ย This is important because unitย oral immunotherapy and oralย immunotherapy in general is aย long-term therapy.ย Adherence to treatment is veryย important.ย If patients discontinue for aย long periods of time they canย lose part or even all theirย tolerance.ย A lot of times adherence toย high doses can be difficult.ย This was the reason the studyย was performed.ย The investigators wanted to seeย if patients could get away withย lower dose maintenance doses.ย The study was encouragingย because it showed similarย efficacy for high and lowย maintenance dose with betterย adherence on the lowย maintenance dose arm.ย We talk a lot about peanuts.ย There are hundreds of studiesย now looking into peanut oralย immunotherapy.ย What is happening with the restย of the food allergens?ย Happily, nowadays we haveย studies that have focused onย different food allergens suchย as tree nuts.ย This was a nonrandomized studyย that looked into desensitizingย patient.ย There were 50 patients betweenย the ages of 4 to 25 years.ย 15 controls in the study thatย received no therapy.ย The target dose was 4000ย milligrams, which isย approximately equivalent to 16ย cashews.ย The investigators reported thatย 88% of the participants whoย received oral immunotherapyย versus zero in the control armย were able to tolerate the doseย of 4000 milligrams of cashewย protein at the end of theย study.ย Those patients that were fullyย desensitized were split into aย high and low maintenance doseย group just as in the previousย study with the peanut.ย They were challenged to a fullย cashew dose.ย It was found that all patientsย who had consumed a low cashewย dose were able to pass a fullย dose cashew challenge after atย least six months ofย maintenance.ย The results were pretty goodย for cashew as well.ย A reported 18% of patientsย received epinephrine associatedย with treatment related allergicย reactions.ย What about those food allergenย — allergies that don’t stayย with most people but resolveย over time and have a naturalย history that is favorable?ย One of those is hands egg —ย hen’s egg.ย This was published in 2012.ย A randomized controlled trialย that included 40 active and 15ย placebo individuals, allย children in the age was —ย median age was 7 years.ย A rush phase, a buildup phase,ย and a maintenance phase of twoย grams of egg powder, equivalentย to a third of a whole egg.ย After 10 months of therapy,ย there was a challenge to fiveย grams of egg powder.
A much higher dose andย maintenance, more than double.ย It was noted that 55% of theย children were able to pass theย challenge.ย They were able to tolerateย approximately the equivalent ofย one whole egg.ย About a year later, they wereย re-challenged.ย This time to 10 grams of eggย powder, double the dose of theย previous challenge.ย Five times the dose of theirย regular maintenance.ย At that point in time 75% ofย the group that was challengedย were able to tolerate thatย dose, which is approximatelyย equivalent to two whole eggs.ย More individuals were able toย tolerate the food challenge.ย They were able to tolerateย higher doses as well.ย The study assessed sustainedย responsiveness or omission,ย which is based a check to seeย if patients can tolerate theย same dose if the therapiesย stopped for a certain amount ofย time.ย The patients for thisย particular study wereย instructed to avoid all egg forย four to six weeks and the foodย challenge was repeated.ย You can see that by stoppingย therapy for this amount of timeย at 24 months when the challengeย was repeated a much lowerย percentage are able to tolerateย the 10 gram doseย .ย There were no severe reactionsย during the study.ย There is a lot of conversationย that has been going on for aย while, especially with regardsย to sesame and sesame allergicย individuals.ย We are seeing more studiesย focusing on immunotherapyย coming through.ย In included 60 patients thatย were receivingย — receiving no therapy forย the sesame allergy.ย The patients were four yearsย and up.ย 88.4 percent were successfullyย desensitized to 4000 milligramsย of protein versus zero in theย control arm.ย Again, the patient’s that wereย desensitized were instructed toย try either the high-dose orย low-dose maintenance.ย Again, low-dose maintenance wasย found to be successful atย equally effective or close toย equally effective as high-doseย maintenance dose.ย Epinephrine treated allergicย reactions occurred in thisย cohort and about 16% ofย patients .ย 8.3% of patients were homeย doses.ย Like I mentioned before, Iย think it’s a good time to focusย a little bit more on early lifeย immunotherapy.ย By early life we are referringย to preschoolers.ย Those children that are belowย the age of 4.ย Below school age.ย The reason we are focusing onย this population is one, ourย guidelines have changed.ย We introduce allergenic foods aย lot earlier than we used two inย the past. I remember many yearsย ago when I was training weย advised individuals to notย introduce allergenic foods ifย they were high-risk until atย least the age of three years.
This was advice given toย families and caregivers.ย We realized now that was theย wrong advice.ย The earlier you introduce theย foods the better your outcomesย are going to be in terms of notย developing a food allergy.ย This is one important point.ย We will see more reactionsย likely in the early age becauseย children are introduced foodsย early.ย We did not diagnose peanutย allergy until the age of threeย because that is when childrenย were exposed to it but this hasย changed.ย Since I mentioned earlyย allergenic food introduction Iย want to reassure everyone thatย based on current guidelines noย screening is needed for infantsย before introducing allย allergenic foods and earlyย introduction is safe.ย Studies that have looked aroundย the world in the earlyย introduction have shown veryย safe outcomes.ย Very few infants will haveย significant allergic reactions.ย Going back to early lifeย immunotherapy, this has come upย from the Canadian Society ofย allergy and clinicalย immunology.ย It is one of very fewย guidelines and guidanceย documents that discuss earlyย food OIT.ย Based on the Canadianย guideline, OIT is indicated forย toddlers and preschoolers.ย While they recognize there is aย likelihood of August heย spontaneously growing milk andย egg allergy like was mentionedย before, these allergies, whenย they persist and they don’tย actually go away can cause aย huge burden on patients andย families.ย So the decision on whether toย undertake early food, noย therapy should involved –earlyย food immunotherapy shouldย involve decision-making ratherย than the physician making aย decision on whether these kidsย should receive OIT or not.ย What they are basically sayingย is that early OIT isย well-tolerated, has highย efficacy for the young ageย group.ย Waiting for the food allergiesย to go away is absolutely anย option if that is the choice ofย the parents.ย Also initiating therapy shouldย be considered as an alternativeย option.ย Sometimes we cannot really tellย if they are going to outgrowย their food allergy are not.ย Sometimes we can.ย There are certain high-riskย phenotypes but not always.ย When it does not go away it canย cause problems. What are theย data to support early oralย immunotherapy?ย Early life oral immunotherapy?ย This was one of the firstย studies published on early OIT.ย It included 40 children betweenย the ages of nine to 36 monthsย with peanut allergy.ย They were randomized one to oneย to receive early oralย immunotherapy at either of 300ย milligrams or 3000 milligramย agents dose for 2 — threeย years.ย This is an open label study, noย control group.ย The preschoolers were recruitedย based on a history of a recentย peanut reaction and alsoย positive testing includingย specific IgE and foodย challenge.ย Responsiveness at four weeksย after stopping earlyย immunotherapy.ย This was assessed by aย double-blind placebo foodย challenge up to five grams ofย peanut protein.ย Desensitize Asian rates wereย very high in this —ย desensitization rates were veryย high in this group.ย The rates of sustainedย unresponsiveness were alsoย pretty high.ย As you can see there is notย very much difference in theย rates of sustainedย responsiveness between theย low-dose and the high-doseย maintenance arm.ย The investigators notedย successful oral immunotherapyย was associated with lowerย baseline specific IgE.ย That’s important since we areย looking for biomarkers thatย were — will predict patientย response.ย On the right you can see theย number of adverse reactions andย the type of reactions thatย occur during the study.ย The light gray color representsย reactions that occur duringย buildup.ย The black color representsย reactions that occur duringย maintenance.ย As in most oral immunotherapyย studies, abdominal pain is topย of the list. We often CGIย symptoms that are related toย therapy and adverse events.ย The other important observationย I always take out of this graphย is that most of the symptomsย and reactions actually occurย during the buildup phase andย very few appear duringย maintenance, which is what weย see during oral immunotherapyย studies.ย Adverse events tend to go awayย over time.ย This is another trialย investigating early peanutย immunotherapy.ย It is the impact trial.ย In included 146 children thatย were randomly assigned two toย one to either receive peanutย oral immunotherapy for placebo.ย — or placebo.
These children were challengedย 500 milligrams of peanutย protein.ย In order to qualify for theย study they needed to reactย before the dose provided theyย had a positive challenge.ย They were then started on anย initial dose escalation day.ย That took them from just .1ย milligrams of peanut proteinย all the way to six milligramsย of peanut protein.ย After the initial doseย escalation day was completed,ย they entered the slow buildupย phase.ย Every couple of weeks theyย would be updosed from sixย milligrams all the way up toย 2000 milligrams, which was theย target maintenance dose.ย Once they reached the 2000ย milligrams they entered theย maintenance phase.ย This whole process of doseย escalation and maintenance tookย 134 weeks.ย At the end of that time theyย were challenged again.ย This time to 5000 milligrams ofย peanut protein.ย More than double theirย maintenance dose.ย This challenge aimed to assessย desensitization and was theย primary outcome for the study.ย For those who were successfulย in tolerating the 5000ย milligrams challenge, they wereย then instructed to stop therapyย completely and stop eating anyย kind of peanut for 26 weeks.ย At the end they wereย rechallenged to 5000 milligramsย to assess for emission.ย These are the results.ย On the top you can seeย intention to treat analysis forย both groups.ย On the bottom is a protocolย analysis.ย In terms of achievingย desensitization, 71% in theย active OIT are more successfulย in the primary outcome of theย study versus only 2% in theย placebo arm.ย In terms of remission, 21% wereย successful versus 2% in theย placebo arm.ย Approximately one in five thatย received early OIT achievedย remission.ย Percentages for the protocolย analysis or higher.ย What was really interestingย was, when the investigatorsย looked at what could increaseย the probability of remissionย for participants in the study,ย they found younger aged andย lower specific allergy toย peanut worse associated with anย increased probability ofย remission.ย When they looked at theย analysis and this time brokenย down into different ages, youngย children that had the highestย rate of remission were betweenย one to two years.ย 71%.ย This dropped to 35% for thoseย who were between two to threeย years and dropped to 19% forย those between the ages of threeย to almost four.ย Now one thing I will say aboutย this is the numbers wereย unfortunately quite small.ย This is providing some reallyย interesting insight on startingย therapy early but it would beย very nice to have some furtherย studies investigating earlyย immunotherapy, not just forย peanut but other food allergensย as well and a young age group.ย Ideally below the age of two.ย Adverse event are reallyย important in any therapeuticย trial.ย In oral immunotherapy studiesย we tend to see a lot of them,ย although happily most are mildย or moderate.ย This particular study 98% ofย participants in the peanut OITย active arm had at least oneย dosing reaction.ย The participants that receivedย epinephrine for at least oneย dosing reactions were 22%.ย What about real-world studiesย in this very young group ofย kids?ย Looking at real-world studiesย in preschoolers there are quiteย a few.ย Most come out of Canada.ย The one I have chosen toย present you today.ย This was a Canadian studyย looking at preschoolers betweenย the ages of nine to 17 monthsย who received an oral foodย challenge to 4000 milligrams ofย peanut protein after receivingย therapy for one year, afterย being on maintenance for a yearย of 300 milligrams they wereย challenged.ย Out of the 170 patients, 92,ย 78.6% had a negative challenge.ย Interestingly, 115, 98.3%, wereย actually able to tolerateย accumulated dose that wasย greater or equal to 1000ย milligrams. There were someย adverse reactions noted in thisย real-world study.ย There were 21.4%, 25 childrenย reacted.ย In these children the thresholdย of reaction had significantlyย increased compared to baseline.ย There were two patients thatย received epinephrine associatedย with therapy.ย This represents a 1.7% ofย epinephrine administration inย the study.ย For those of you who are moreย visual, this is the results inย the form of graphs.ย You can see on the left-handย side the effectiveness notedย for 1000 4000 — 1000 and 4000ย grams in the change in theย acumen lidded threshold ofย peanut that was tolerated atย baseline and the follow-up oralย food challenge .
Potential benefits in startingย treatment early include theย development of a higherย threshold for patients.ย This reduces the risk ofย accidental exposures andย increases probability forย desensitization and sustainedย responsiveness before startingย school.ย Is associated with aย psychological benefit.ย Having a more controlledย approach to includingย allergenic food and having aย shift in avoidance requirementsย and reduced socialย vulnerability related to foodย allergy.ย That include bullying, which asย we know it now — no networkย — know now occurs more withย food allergies and thought.ย This can take a long time.ย It can be costly.ย It requires a lot of staff,ย effort and time.ย There are differences inย insurance coverage plans andย physician reimbursement acrossย the country.ย There are areas that haveย limited access to allergyย specialists.ย We are talking to parents here.ย There are a lot of parentalย hesitancy and anxiety,ย especially when dealing withย malady events.ย I will move to a differentย form.ย This is epic you to any of —ย ep icutaneous.ย The Pats contains the driedย allergen in the chamber andย stays there for 24 hours beforeย it is changed.ย It targets dendritic skin cellsย and its been locked into aย single daily dose of 250ย micrograms of peanut protein.ย A much lower dose compared toย that with oral immunotherapy.ย This was the first epicutaneousย immunotherapy trial published.ย Children received the patch forย 12 months.ย You can see the intention toย treat analysis, the successย rate of 35% and those who hadย the patch versus 13% and thoseย on the placebo.ย Looking at side effects, theย most common involved the skin,ย which is expected in the wayย that the allergen is placed onย the skin.ย The anaphylaxis rate was 3.4%.ย This was followed by the peopleย trial and three year termย analysis of 141 subjects thatย received epicutaneousย immunotherapy.ย At month 36, 75.9% hadย demonstrated increased listingย dose.ย If an individual had anotherย listing dose of less than 10ย milligrams at baseline, theย primary outcome would involveย the dose going to at least 300ย milligrams or over.ย For those who had a dose ofย more than 10 milligrams atย baseline, the aim was to bringย the eliciting dose after theย therapy to more than 1000.ย You can see on the graph on theย right that the cumulativeย reactive dose increasesย significantly with multipleย years of therapy, starting atย 144 and going to 444 milligramsย at month 12, and 934 at monthย 36.ย More than enough to protectย them accidental exposures.ย Sustained nonresponsiveness wasย also looked at.ย Importantly, there were noย treatment related epinephrineย events in the years two andย three.ย The study showed goodย compliance.ย The study was done as well forย young infants.ย This is the Epitope study.ย The primary outcome showed 67%ย of infants and taught othersย been successful — toddlersย being successful versus 33.5%ย in the placebo.ย Treatment related anaphylaxisย occurred in only 1.6% in theย intervention group.ย Creative treatment relatedย anaphylaxis for food, therapyย –immunotherapy tends to beย lower in the early age group.ย Moving on to sublingualย immunotherapy.ย This works a littleย differently.ย The doses are much smallerย compared with oralย immunotherapy .ย They were either swallowed orย kept in the mouth for a fewย minutes and then spat out.ย This targets the cells.ย This was the first sublingualย immunotherapy study includingย 40 subjects receiving eitherย slipped or placebo.ย After 44 weeks of therapy itย was found that 70% wereย successful in significantlyย raising their toleratedย threshold versus 15% of theย placebo subjects.
You can see the medianย tolerated dose is significantlyย increased from just 3.5ย milligrams at baseline to 496ย milligrams. This was the medianย tolerated dose.ย After further weeks of therapyย looking at now 68 weeks ofย total treatment, the doseย increased to 996 milligrams.ย More importantly, there were noย noted severe reactions duringย this study.ย This is a difference withย severe reactions.ย They are exceedingly uncommon.ย You can associate that with theย way the treatment isย administered.ย Epinephrine treated reactionsย are few and far between.ย In most studies they wereย actually none.ย This is the study looking atย sublingual immunotherapy.ย Again, some results.ย Children between the ages of 1ย ti 1 — to 11.ย 70% could target — sideย effects are similar to previousย studies with symptoms being theย most common.ย Let’s move onto biologics.ย I’m sure everyone by now hasย seen the results of the trialย that looked at efficacy ofย Omalizumab.ย The primary endpoint for theย study was ingestion of peanutย protein in a single dose of 600ย milligrams or more withoutย having any dose limitingย symptoms. The investigatorsย looked at various secondaryย endpoints.ย There were children and adultย included in the study.ย They all needed to be peanutย allergic and also have at leastย two other food allergies,ย including potential forย cashew, milk, egg, wheat andย hazelnut.ย 300 milligrams or less for twoย other fruit.ย They were randomly assigned toย either receive Omalizumab orย placebo at the two to oneย ratio.ย The first 62 participants wereย enrolled in a 24 week openย label extension.ย A total of 462 were screened.ย 180 randomized.ย 177 were children andย adolescents.ย There were three adults in theย study.ย I think we were all interestedย to see the efficacy resultsย when you look at the primaryย endpoint that refers toย tolerance of peanuts withoutย any dose limiting systems —ย symptoms. Those receivingย Omalizumab achieved 600ย milligrams of peanut proteinย versus 7% in the placebo arm.ย When looking at other foods,ย cashew percentages, 41% versusย 3%.ย Eggs, 67% versus 0%.ย It is difficult to cover theย study in a presentation likeย this.ย I encourage everybody to lookย at it in more attention.ย We could literally dedicate aย whole presentation to each oneย of the studies are presentedย today.ย These are more detailed resultsย looking at the different foodsย and different doses tolerated.ย The investigators have alsoย looked at tolerance of one foodย at a certain amount versus twoย foods versus three foods.ย The percentages start offย pretty high, especially forย doses over one gram.ย Then they dropped down to lowerย after you move on from the oneย gram to two, Four to six grams.ย I will spend my last fewย minutes talking a little bitย about decision-making in foodย allergy management.ย Remember the title of thisย webinar was individualizedย management.ย We know now what works for oneย family and one individual mayย not work for others.ย Shared decision-making has comeย into our practice and is partย of our standard consultationย for many years now.ย Both clinicians and patientsย have an equal roll to a play inย the optimal goal which isย informed decision-making basedย on the patient once.ย — wants.ย The clinician hasย responsibility of making aย correct diagnosis of foodย allergy, discussing optionsย that are available with theirย patients.ย Looking for any conflict andย also referring.ย Needed.ย — referring for support ifย needed.ย The patient has to identify andย communicate their own informedย values and priorities.ย These are often shaped byย social circumstances.ย These are practical steps I useย in my clinic when it performย those shared decision-makingย conversations.ย I start by saying to myย patients let’s discuss thisย together because it’s a two-wayย communication between patientsย and physicians.ย It’s important to listenย actively to what the patient’sย have to say.ย As a second step we examineย options together.ย I usually say let’s examineย your options and what isย available now, what choices youย have.ย We go through benefits andย risks for different options.ย We talk about available choicesย and alternatives.ย Step three can occur on theย same visit or a future visit.
Sometimes quite a few timesย decision-making does not takeย place in one singleย consultation.ย When the patient is ready toย make a decision then they willย communicate that to me, to theย physician, and after followingย all the steps together we feelย like the decision is the mostย appropriate based on the goals,ย preferences and values.ย There were a lot of differentย decisions that can fall intoย this.ย Shared decision-making process.ย An example of one would beย choosing versus therapeuticย options and management optionsย for food allergens.ย Avoidance, oral immunotherapy,ย Omalizumab.ย The future will bring even moreย of these into play.ย I have listed some of theย considerations and discussionย points we can bring togetherย with patients.ย Another example would beย discussing a high versus lowย dose OIT and I presented a lotย of the data availableย discussing this.ย It’s important to remember thatย your goal, the patient’s goalย is the one that is going toย determine which option youย choose.ย For those who are onlyย interested for protection fromย accidental exposure, it reducesย the chance of accidentalย exposures.ย For those aiming for free diet,ย we’re looking more forย sustained unresponsiveness andย remission.ย This is a differentย conversation and the steps thatย need to be taken in the clinicย are quite different.ย I have included this reference.ย The study that gave us someย information about a reductionย of risk to accidental exposuresย in terms of high-yieldย threshold changes afterย therapy.ย To round this up I need toย remind everyone that when weย are making decisions about foodย allergen management it is notย all targeting therapy.ย Of course therapies are a bigย part but there are otherย decisions that involveย management that are associatedย with food allergies.ย For example, what to do if youย have an Apple elected reactionย — an anaphylactic reaction.ย This comes out of the update ofย the anaphylaxis parameter, thenย excellent document I encourageย everyone to read.ย It actually comments on theย need for activating emergencyย services in an episode ofย enough Alexis — anaphylaxis.ย Looking at episode relatedย factors, is there a promptย response to a single dose ofย epinephrine?ย Is there complete resolution ofย symptoms following the singleย dose of epinephrine?ย What about other factors likeย does the patient have immediateย access to more than one dose ofย F and Efrin?ย — epinephrine?ย Do they have a goodย understanding of whenย epinephrine should be used andย what the benefits are whenย using it early?ย Is there immediate access toย other people who may provideย help?ย These are very importantย factors to consider whenย discussing activation of theย emergency services forย anaphylaxis.ย We have learned a lot andย during the COVID-19 pandemic weย were member how the patient didย not want to activate emergencyย services, did not want to go toย the emergency room.ย A lot of that experience hasย informed our most recentย conversations and also theย updates in the anaphylaxisย parameter.ย In conclusion, the landscape ofย food allergy management hasย changed significantly over theย past three years.ย There are different options nowย available.ย Those options can often beย confusing for patients.ย I haven’t asked recently if,ย for example, the new biologicย can be taken orally.ย It is not necessarily intuitiveย and don’t always be certainย people are receiving theย correct information.
There is a lot ofย misinformation out there thatย we need to tackle successfully.ย We are the ones as allergistsย that have the evidence that canย actually cancel outpatient —ย out patients based on it.ย I cannot really stress thisย enough.ย We don’t give the sameย judgments to all of ourย patients.ย We give them the same optionsย available but what they decideย to do a be very different.ย The other ones that are goingย to guide us towards a finalย decision that reflects theirย values and priorities.ย In terms of unmet needs andย future research, I am sure weย can find a lot more than what Iย have put here.ย I just wanted some examples.ย I think we would all benefitย from head-to-head studies thatย will examine efficacy andย safety of different therapies.ย I would love to see some ofย those.ย I would like to see some largerย studies which include diverseย food allergy populations soย that we can have much betterย insight into individualย management.ย We can’t really makeย assumptions about a lot ofย these things.ย We may think patients requireย option A, but then we find outย that actually that was not trueย .ย I think a lot more research isย required in this space and willย definitely be welcome.ย I would love to see studiesย that are focused on patientย reported outcomes.ย Again, most studies are lookingย at efficacy and safety.ย Those two are stream theย important.ย We still need to look at them.ย Patient reported outcomes areย also key.ย This is something that onlyย they can report to us.ย They only come from them.ย We cannot guess, cannot assume.ย Thank you very much forย listening to me.ย Thank you for your attention.ย I am not very happy to answerย any questions and the remainingย time.ย Thank you.
Catherine:ย Dr. Anagnostou, we have a lotย of questions that I’m not sureย we will be able to get to themย all by 1:00 but we will do ourย best. The first question wasย asked.ย Excuse me.ย What is the feasibility ofย doing PNET OIT — peanut OITย when the child vomits peanutย butter?
Dr. Anagnostou:ย None.ย I can answer that in one word.ย This is a case where you’reย looking it individualizedย management.ย If the patient has a tasteย aversion to the food, they willย not eat it.ย You are not going to force-feedย them even if the parents mayย offer.ย I have had that offer in myย clinic as well.ย I immediately said no.ย You have to look at the patientย factors.ย That was part of theย decision-making.ย If you have a picky eater, ifย you have a child with severeย taste aversion or any kind ofย limitation to digesting foodย than pursuing oralย immunotherapy would not be theย right choice at that point inย time to put it mildly.
Catherine:ย OK.ย If a person is desensitized toย one allergen does that bodeย well for successful OIT forย other foods to which a child isย allergic?
Dr. Anagnostou:ย Excellent question.ย We have looked into what weย call cross decentralization.ย There are certain foods thatย share common proteins andย common allergens.ย For example, tree nuts.ย There are common proteinsย shared among different treeย nuts.ย We all know that patients whoย are allergic to cashew, a lotย of times, although not alwaysย or also allergic to pistachio.ย Same for walnut.ย We call that cross-reactivity.ย For therapies we are reversingย that term to crossย desensitization.ย There have been oralย immunotherapy studies haveย looked into desensitizingย people to cashew.ย They find the majority are alsoย desensitized to pistachio.ย There is this part of theย question where foods that areย closely related botanically canย be cross desensitized.ย In terms of desensitization toย irrelevant foods, when you doย oral immunotherapy to peanutย you are not going to crossย desensitized anybody to milk.ย The foods are not relatedย botanically.ย It is unlikely you will seeย that effect.ย They will also be no indicationย as to how successful the OIT isย going to be in those veryย different foods.ย What I have to say however isย that the efficacy of oralย immunotherapy is pretty high.ย Looking at research studies,ย the percentages are almostย always above 60% to 70% to anyย kind of food.ย When looking at multi-foodย studies with multiple foodsย given concurrently, the ratesย are equally high.ย Generally, it works and itย works from a variety ofย different foods.ย I hope that answers theย question in a different way.
Catherine:ย OK.ย How should eggs be introducedย to infants?ย If a sibling is alerting toย peanut or egg, are thereย guidelines to counsel theย family?
Dr. Anagnostou:ย There is a lot of informationย nowadays from both the AI andย college.ย There are leaflets you canย print out to handier patients.ย I’m assuming the questionย refers to potential crossย contact or cross-contaminationย of surfaces when there isย already a child in the houseย that is allergic to one ofย those food allergens.ย I know there are a lot of fearsย surrounding this but I alwaysย tell me families that they canย wipe down surfaces quiteย successfully just using waterย and soap, therefore avoidingย this type of cross contact orย cross-contamination.ย Other safe approaches likeย there is a five-year-oldย allergic tag.ย Now the family has a new infantย they want to introduce egg.ย They can probably do that andย introduce boiled egg to to theย infant.ย They could choose a time withย the other child is out of theย house of they are so incrediblyย worried, although I don’t thinkย that would be necessary.ย It is of incredible importanceย to do early allergen includeย introduction.ย I encourage all families to doย it.ย There are multiple practicalย ways to overcome theseย barriers.
Catherine:ย We are just at the top of theย hour.ย We don’t have time for any moreย questions.ย Thank you Dr. Anagnostou. Thisย has been so informative.ย Just a close, join us nextย month on June 12 at 4:00 p.m.ย Eastern standard Time.ย We will welcome a doctor toย discuss the relationshipย between atopic dermatitis andย allergies.ย You will receive an evil fromย Zoom — and email from Zoomย with a recording and valuationย and supplement resources.ย Thank you again for joining us.ย From all of us at Allergy &ย Asthma Network, join us as weย work everyday to breathe betterย together.ย Thank you.ย Have a good one.