This webinar was recorded on Tuesday, September 27, 2022
There are advances in the care of food allergies. Join us as Dr. Anagnostou brings you vital information on the current treatments and management strategies for food allergies and take a look at the future of treatment.
- Dr. Aikaterini Anagnostou
Sponsored by the American College of Allergy, Asthma and Immunology
Transcript:This transcript is automatically generated. 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.
Speaker 1 (00:04)
This is Sally Schoessler, Director of Education for Allergy and Asthma Network. Today’s webinar helps Allergy and Asthma Network live out our mission to end the needless death and suffering due to asthma, allergies and related conditions through outreach, education, advocacy and research. Food allergies are a health concern that need attention 24 hours a day, seven days a week. Families that manage an allergy to food often find it a struggle to maintain the constant vigilance needed to avoid having exposure to an allergen. Today we’re going to hear about current and future food allergy treatments that may help to relieve some of this burden. We are pleased to welcome today’s speaker, Dr. Aikaterini Anagnostou. She is an associate professor of pediatrics at Texas Children’s 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 passionate about investigating new and innovative treatments for food allergy. She is currently the principal investigator for phase three trials of peanut oral immunotherapy and is leading research projects on food allergy, anaphylaxis and the microbiome. Dr. Anagnostou obtained her PhD from Cambridge University in the United Kingdom and her dissertation focused on two separate trials of peanut oral immunotherapy in children.
Her research work was published in The Lancet and received international recognition. Thank you so much for being with us today and for sharing your knowledge and expertise on this important topic.
Speaker 2 (01:47)
Thank you so much Sally, for the kind introduction. It’s my pleasure to be here and I’d like to welcome everyone as well to today’s webinar. So I will be focusing on food immunotherapy mostly as today’s topic for food allergy therapies. But I will also briefly mention biologics and some combination therapies so that we’re all on the same page. I’m just going to very briefly explain some terms that are used in food immunotherapy. So one is desensitization. When we talk about desensitization, we are referring to an increase in the threshold of reactivity of patients before therapy compared to after therapy. And generally patients are able to tolerate larger amounts of the food they’re allergic to after successful desensitization. Sustainable responsiveness or a mission as it is now called, is a little bit different. So it refers to stopping immunotherapy for a period of time and that can differ in different studies. It can be anywhere from a few weeks to a few months. And then when the patient restarts immunotherapy and they’re able to eat the exact same dose that they were eating before they stopped, then we say that that patient has achieved sustained non responsiveness or emission.
Long term tolerance is a goal that we haven’t really reached yet. With any form of food immunotherapy, it implies that you’re able to eat the food whenever you want, stop for however long you want and go back to eating it again. Eat as much as you like. So consumption without any problems or reactions. There are different routes that we administer food immunotherapy through. So one of the most studied, of course, is oral immunotherapy. So sublingual immunotherapy is another one and also percutaneous and I will be discussing all these three, one after the other. So let’s start with oral food immunotherapy. And this is what our typical oral immunotherapy protocol looks like. So there are different phases to oral immunotherapy. The first one is a so-called rush phase or initial dose escalation phase. And this usually lasts either one day or a couple of days. And the idea is that we start from very small doses, very few milligrams of the dose for the food the patient is allergic to, and very quickly, within, say, 20 or 30 minutes, we escalate to a higher dose. This is done over a period of a day, usually in hospital or in a clinic.
The initial dose escalation is followed by the build up phase. Now, during this phase, the dose is increased again, but this time the increase is done more slowly. So during the build up phase, the doses usually increase either every couple of weeks or every month. This differs in different protocols, but the idea is that you go slow up until a target dose, a top dose, which can be predefined in the protocol. So, for instance, for patients with peanut allergy, studies have looked at the top buildup dose of 300 milligrams. That’s a very common dose, which is approximately one large peanut or two very small peanuts. And then once you reach that dose at the end of the build up phase, you enter the maintenance phase. Now, during the maintenance phase, there’s no dose increase. So patients and study participants will take that same dose every day for many months or years. And a lot of patients ask me in clinic, how long do I have to take this for? And at the moment, based on the information we have, we think most likely lifelong, unless something changes in the next few years. Now, some studies, but not all, have also assessed sustained unresponsiveness, so they stopped treatment, like I mentioned before, from anywhere between a few weeks to a few months, and repeated a challenge at the end of stopping treatment. And they checked at what dose the patient or participant is reacting and they compared that dose to the end of this institution period. If the participants had the same level of reactivity at both challenges, then they were considered successful in achieving sustained unresponsiveness or emission. If they were able to eat a lower dose, but still higher than their initial threshold of reactivity before the therapy, they were considered desensitized. I hope this makes sense to everyone, but please do ask questions if it’s not clear. So this is a palisade trial. It’s very well known. Now, it’s a multicenter trial that looked into peanut oral immunotherapy as a form of therapy for peanut allergic children and adults. The majority of subjects were actually children, although some adults were also included in the study. The primary outcome for this trial was the ability of participants to tolerate a single 600 milligram dose in the exit challenge of the study and the cumulative dose they could eat at that level was approximately just over a gram of peanut protein.
Speaker 2 (07:10)
67% of participants in the active arm, which is represented here in this dark blue color, achieved this primary outcome. In the placebo arm only about 4% were able to achieve this outcome. Secondary outcomes included tolerance of a dose of 300 milligrams and also 1000 milligrams. And you can see that obviously the percentage of those who were able to eat 300 milligrams was higher because this was actually the maintenance dose for the Palisade study. Whereas the ability of those who were able to eat 1000 milligrams was a little lower because this is much higher than even the primary outcome of 600 milligram dose. On the adult side there were also differences between active and placebo arm but because the numbers were quite small, these differences were not statistically significant. So I think that we need a lot more studies in adults before we can actually decide what sort of level of desensitization we’re able to achieve. This is a table that lists adverse events during the Palisade study and of course as both physicians and investigators, we are interested to find out what is happening to our patients in terms of side effects of any new therapy or treatment.
And as you can see, there are side effects from pretty much everybody’s system which is expected in OIT studies. The majority of these tend to be mild or moderate. Anaphylaxis in this trial occurred in 14% of patients and I have highlighted this top part of the table here to show you that the most common symptoms during oral immunotherapy were coming from the gastrointestinal system. Again, this is expected because we are using the oral route for this therapy. These symptoms from the GI are also the most common reason why people would discontinue oral immunotherapy so it’s quite important to point them out. So as I mentioned at the beginning, this is likely a therapy that patients will have to maintain for long periods of time if not for life. And like any other long term treatment, it poses quite a few challenges, especially in terms of compliance and it is hard for people to remember to take a dose of anything really on a daily basis. So it was thought that it would be nice if we could actually reduce the burden of daily dosing for patients and maybe be able to advise them to take a sort of lower frequency dosing.
Speaker 2 (09:53)
So alternative dosing regimens were studied and this is one of the few studies that has done just that. This was a follow up study to the Palisade. So everybody who completed successful desensitization in the Palisade study could be eligible for this follow up study and participants were divided into different cohorts. So you can see here on the diagram cohort one were the first 120 participants and they actually continued daily dosing for 28 weeks. Then cohort two had a slightly different regimen, four weeks of dosing every other day and then 24 weeks of twice weekly dosing. And in cohort three, there were three sub cohorts; one that continued daily dosing for a total period of time of 56 weeks. A second that had a combination of dosing, four weeks of daily dosing, 24 weeks of every other day dosing, and then 24 weeks of biweekly dosing. And the last cohort, the three C cohort that had four weeks of daily dosing, 24 weeks of every other day dosing, and between 24 to 56 weeks of twice weekly dosing. I’m just going to draw your attention to the colors. Think of orange as the daily cohort color and gray as the non daily.
Speaker 2 (11:23)
Most of the comparisons that are done in this paper refer to daily versus known daily cohorts just to make it easy for everyone. So I’ve summarized the results on this table. For those who continued on a daily regimen, more than 70% were able to tolerate a 600 milligram dose and also 1000 milligram dose and a 2000 milligram dose was close to 70% as well. But when you look at the nondaily regimen, the percentage here is not as different but there is a wide range. Patent is for 1000 doses, definitely much smaller and then when you go to higher doses like 2000 milligrams again the percentage for the nondaily resume drops quite a bit. So it was concluded at the study exit that daily dosing was associated with lower rates of adverse events and fewer severe systemic allergic reactions compared with non-daily dosing. Most common symptoms were coming either from the gastrointestinal or respiratory system and severe adverse events were happily fairly infrequent for participants in both groups. But most importantly, you could see when the comparison was made between those who maintained a daily dose versus those who were having non daily dosing that the efficacy tends to drop as well and the ability to tolerate higher doses is lost when you are on a non daily regimen.
Speaker 2 (12:55)
So what about non responders? So what happens to those who were assigned to a non daily regimen and started having allergic reactions and how many were they? So there were 18 people who did not really tolerate non daily dosing out of 113 that were assigned to it and those were all switched back to daily dosing. When you look at participants who suffered from anaphylaxis in the different groups, there were two subjects in the daily cohorts out of a total of 143 and three subjects in the non daily cohorts out of a total of 113. All of these participants who experienced anaphylaxis received one dose of epinephrine and symptoms resolved and most importantly, some cofactors were present in four of these patients and those were illness, fatigue and exercise. And I will discuss cofactors separately in a couple of minutes. This is just a visual representation of the maximum symptom severity at the food challenges at different dosing levels. And again, the dosing cohorts are split. So these two are the daily ones and these ones on the right are the non daily ones. I focus on this dark green color because this represents severe symptoms, whereas all the others are sort of no symptoms or mild symptoms.
Speaker 2 (14:20)
So you can see at the 600 milligram dose already there are a few severe symptoms during the food challenges for the non daily dosing cohorts. The same goes for the 1000 milligram dose. When you go up to 2000 milligrams then you can start seeing them in the daily dosing cohorts too, although they are much less. This bar here I’m not referring to. These were placebo subjects in the parent study that were just continuing OIT. So that’s why I’m not referring to this at all. So what about external factors? Now, we’ve noticed as we were doing more and more research studies on oral immunotherapy, that sometimes certain external factors will unbalance this success in desensitization. And patients who were tolerating, let’s say, 100 milligrams of protein would suddenly start having reaction to that level if, for instance, they were very tired or if they were exercising very close to the dose, or if a viral illness sort of came in. And this was more of an empirical observation, but it was confirmed after this study came out. And this is a study called Trace Peanut Study that was performed in the United Kingdom and looked at how threshold changes with some of these external factors.
Speaker 2 (15:48)
They took adults with peanut allergy, not immunotherapy patients, just peanut allergic patients. They challenged them first to establish the threshold, they found the reactive threshold and then they sleep deprived them and challenged them again. And they noticed that the threshold dropped by more than 40%. And the same happened with exercise. When the same patients who were tolerating a certain threshold were exercised and then ate their allergen, the threshold dropped again by more than 40%. So this is one of the very few studies that confirmed our suspicion that some external factors, like the ones I’ve described, can actually alter the balance between the dose that is maintained in OIT and cause trouble. We now inform, of course, our patients about these and we educate them. And the advice is that if, for instance, you experience a viral illness, you either stop dosing or drop down your dose. Call your physician for further advice. We also advise against exercising for 2 hours after eating your dose. And these are some of the limitations in oral immunotherapy, sustainable responsiveness or emission was studied in this small pilot study of two different U. S. Centers that included 24 subjects, all children, one to 16 years old, that had received oral immunotherapy subpoenas for five years.
Speaker 2 (17:21)
So the treatment was stopped for a month. And after that, another challenge was performed to see at what level the patients were reacting now. And it was shown that 50% were actually able to pass the challenge and maintain the same dose that they had before stopping therapy, which I think is actually quite impressive. The most interesting thing that came out, though, was that even for those who actually failed the challenge, so they lost some of the desensitization. The actual threshold at which they had trouble was way higher than their baseline. So the median set of baseline for most of these kids was 50 milligrams of peanut protein at baseline. But when they were challenged after stopping therapy for a month, it was 3750. So clearly, for a lot of patients, desensitization is not lost as fast as we initially thought. One of the important factors that we look at any form of new therapy is what effect it has on quality of life. And we all know that the quality of life of our food allergic patients is not very good. There are different domains that are affected by the food allergy, including, of course, all the dietary restrictions they have to adhere to because of avoidance, emotional impact, social restrictions and limitations, and of course, all the anxiety and fear that come from mercury accidental exposures.
Speaker 2 (18:53)
So studies have looked at quality of life before and after immunotherapy. And these two that I have put up here look specifically into oral immunotherapy. And you can see the study on the left shows an improvement in quality of life for multiple of those domains post peanut, oral immunotherapy for children with peanut allergy. And the same for this study here, which is actually coming from Israel, that looked at a cohort of patients who received immunotherapy and looked at quality of life before, during and after. And this is the total score for quality of life. It is up here for baseline. I hope you can see my pointer. And then it goes all the way down here after maintenance and follow up. So there’s a decrease in the quality of life score and this is interpreted as an increase in quality of life. So quality of life got better following successful immunotherapy and desensitization. Protection from accidental exposures is one of the most common goals for patients and families seeking therapy for food allergy. They want to basically get rid of that fear that if they accidentally get exposed to a food that contains their allergen, they will have a severe reaction.
Speaker 2 (20:17)
And this was a mathematical model that looked at how your risk to having a reaction from accidental exposure changes post immunotherapy. So let’s assume that we have a patient who reacted to 30 milligrams of peanut protein at baseline. This side here shows the baseline threshold doses and then following successful desensitization, this same patient is now able to have 300 milligrams of pena protein without reacting. So we are going all the way here oops, sorry about this. We’re going all the way here and we see that the reduction in the risk of having a reaction to accidental exposure for that patient is now 98.5 per cent. And if you look at this same patient tolerating 1000 milligram dose, the risk reduction is 99.9%. So clearly achieving thresholds of 300 milligrams and 1000 milligrams of peanut protein is clinically relevant and also significant to patients following successful immunotherapy. So I put up this summary here so we can compare the different routes of food immunotherapy. So for OIT, we know that this is an intervention that has high efficacy. The large majority of patients will be successful in achieving desensitization. We know that desensitization occurs usually within a few months.
Speaker 2 (21:51)
So reasonably fast larger amounts are tolerated over time. There are also less side effects over time and a lot of people sometimes focus on the acute phase, as I call it, of OIT, which is mostly the rush and build up phases. And those are in a way the most difficult ones because they have the more side effects. But as time moves on and patients move on to maintenance, the side effects decrease significantly. We know now that higher desensitization rates and also fewer side effects are associated with daily versus non daily dosing. So this is something we can discuss with our patients. There is a protective effect against accidental exposures that is clinically significant improvement in quality of life have been shown by various studies and OIT is currently licensed for four to 17 year olds, but a lot of studies are coming through for younger ages as well. And over the last two to three years we have had more studies coming through for infants and toddlers who have shown very promising results. And it actually seems like the earlier you start, especially in that kind of early age window of preschool children, the better your results in terms of both desensitization and remission of sustained unresponsiveness.
Speaker 2 (23:15)
On the other hand, this is an intervention that is associated with frequent side effects, although we should remember that most of those a mild or moderate intend to wean over time. Anaphylaxis has been reported in 14% in the Palisade study, but higher rates have been shown in other research studies. So this is something to keep in mind. There may be a population effect here. There are practical limitations for OIT and we discuss the external factors and what effect they can have. And there’s also a risk of eosinophilic esophagitis, I didn’t discuss this in detail. We are still in sort of early stages of trying to understand what is happening with EOE and studies have shown sort of percentages of people developing EOE between 3 to 5%, although some have shown higher than that. But it’s kind of difficult to gauge whether this is sort of undiagnosed EOE that got triggered by the initiation of immunotherapy or EOE that actually developed as a consequence of the therapy or even an undiagnosed EOE that was just not noted until this happened. A systematic review that looked at different OIT studies quoted a rate of 2.7%. When EOE was looked at recently in some otherOIT studies, like a group of other It studies, the rate was about 5%.
Speaker 2 (24:48)
The problem is that a lot of patients that have this type of symptoms will just stop therapy and not necessarily go into having a biopsy. So it’s very difficult to confirm it. So we may be over or underestimating it. And some investigators have also published that for some of their patients, reducing the dose actually makes all these symptoms disappear and patients then continue therapy without problems. And this has been called EOE like syndrome. I’m happy to discuss this further in a Q and A session if you have more questions. Most importantly now for all forms of immunotherapy, including the oral, we don’t really know what protection we get against very large extensible exposures. We think that likely less severe reactions occur after desensitization. But no one has looked at this in a systematic way. Also, oral immunotherapy is not a cure. No matter what we see in the media. It doesn’t make theology go away and it doesn’t cure it. But it does allow patients to eat larger amounts of food that they would normally be able to. You cannot get rid of your epinephrine. This is what I say to all my patients, and it’s one of the most common questions, especially from adolescents.
Speaker 2 (26:07)
Continuous carriage of epinephrine is important because although reactions sort of decrease significantly during maintenance and anaphylaxis follows the same pattern, it may still occur. So it is very important that patients still carry their emergency medication with them. Okay, let’s gears a little bit now and discuss sublingual food immunotherapy. So how does it work? It works in a similar way to oral immunotherapy in terms of gradual dose increases to a maintenance dose. So again, we go sort of low and slow, but the doses here are minimal. So compared with the OIT, they’re between 100 to 1000 times smaller. And the doses can be swallowed or they can be kept in the mouth for a few minutes and then spat out because this type of treatment targets the oral angel hand cells in the oral cavity. So this is a study of sublingual immunotherapy that included 40 subjects, both children and young adults, and they received either daily peanut or placebo. They were split equally, 20 and 20. And after 44 weeks of treatment, they all underwent a challenge to 5 grams of peanut protein. And after those 44 weeks of treatment, 70% of the active subjects were successfully desensitized versus 15% on the placebo arm.
Speaker 2 (27:34)
And the median tolerated dose increased from only 3.5 milligrams of peanut protein all the way to 496 milligrams. Then participants received sublingual immunotherapy for a total of 68 weeks. So they continued their treatment on maintenance dose and the tolerated dose, the median tolerated dose that was calculated after 68 weeks of treatment had now increased to 996 milligrams or almost doubled. So the longer you treat with SLIT, it seems like the larger doses you are able to tolerate. And when looking at the safety profile, most of the side effects are oropharyngeal. And remember how we said that in oral immunotherapy it’s the GI system that gets affected here, it’s sort of the oral cavity that gets affected. So you get oral itching and maybe throat itching because this is how we are giving the doses. And most importantly, when you look at severe reactions, there were none in this study. This is a newer study that included 37 subjects aged one to eleven, that completed between three to five years of peanut SLIT and 67% of those successfully consumed 750 milligram or more during the double blind challenge. And the safety profile is very similar to the previous study with local reactions such as lip swelling and oropharyngeal paritis being the most common and no use of epinephrine.
Speaker 2 (29:09)
So looking in this SLIT, it has lower efficacy and it takes longer, but it does allow for moderate to higher amounts to be tolerated over time. There are certainly less side effects compared with OIT and these are mostly orpharyngeal. There is a variable protective effect against accidental exposures. This is mainly because it takes longer to work and we’re not really sure how many people are up to the level of, say, 300 milligrams of peanut protein, which provides protection from exposures. So we have to say that it is variable, at least for the first year. But on the other hand, there are no practical limitations here. So patients receiving slip, they don’t need to avoid exercise, don’t need to worry too much about illness. Anaphylaxis is also rare. It has been described especially for some slit milk studies, but it is pretty rare. Still, we have unknown protection against large exposures similar to OIT, mainly because this has not been studied. Quality of life has also not been studied with SLIT, but I’m pretty sure these studies are coming. And again, it is not a cure, it doesn’t make the algae go away and patients still need to continue carrying their epinephrine.
Speaker 2 (30:30)
So let’s move on to epicutaneous food immunotherapy. This works a little bit differently than the other two in terms of how you receive the allergen. So there is an occlusive patch, and I put the picture of it right there, contains dried allergen in the chamber and this patch is applied on the child’s back, so it’s applied on the skin every 24 hours. It targets the dendritic skin cells and it provides a single daily dose of 250 micrograms of peanut protein. So as you can see, a very, very, very small dose. The annual exposure amount is approximately a third of a peanut. So this is, again a very well known study. By now, that Pete’s trial that looked into epicutaneous immunotherapy and use of patch for a year. The primary outcome here is based on the eliciting dose and the patients were split into two groups. Those who were reacting to less than ten milligrams of peanut protein at baseline. And the primary outcome for those was to achieve more 300 or more milligrams of peanut protein after therapy. And those who had a higher threshold and they were reacting to between ten and 300 milligrams at baseline.
Speaker 2 (31:51)
And the outcome for those was to achieve 1000 milligrams or more of peanut protein after a year of therapy. So the changes were on the eliciting dose. So what were the results? In the intention to treat analysis? It was shown that 35.3% of patients were successful to achieve the primary outcome after twelve months of therapy, compared to 13.6% of patients in the placebo arm. When looking at the safety profile, most of the side effects were coming from the skin and again, as expected, these were the most common ones, paritis sort of skin itching and Aristema. Serious and severe adverse events did occur, but they were pretty uncommon and the rate of anaphylaxis was 4%. So what happens long term with EPIT? This is a three year interim analysis of the subjects who continued receiving EPIT for up to three years. And I think the best way to visualize this is looking at the graph on the right. So this is the baseline tolerated. The median sorry, eliciting dose was 144 milligrams of peanut protein. Then at the end of year one this had increased to 444 milligrams and at the end of year three this went all the way up to 944 milligrams.
Speaker 2 (33:22)
So there is an increase in the cumulative reactive dose over time, but two to three years of treatment are likely required to bring this up to a level of about 1 gram. The investigators also looked at remission after two months of therapy. It was a small number of subjects that participated in this, only 18, but 14 out of those. So 77.8% actually were able to maintain an elicited dose of equal or more to 1 gram, which is quite impressive. There was no treatment related epinephrine use in years two and three and compliance appeared to be pretty high with very few withdrawals of therapy. Quality of life has been looked at for EPIT and again it seems that successful desensitization as a result of epicutaneous immunotherapy is associated with a significant increase in quality of life. And the graphs here, the top graph shows the parent reports for quality of life changes and the graph here shows the child report. So a proxy report was received from pretty much everyone who participated child report. Not as much, because very young children of course cannot fill in those questionnaires, but both of these showed increases in quality of life and this was mainly driven by the increasingly eliciting dose and also by achieving.
Speaker 2 (34:54)
The primary outcome. There was a study that also looked at how your risk to exposure to packaged food that is cross contaminated with your allergen changes after successful epicutaneous immunotherapy. And there was a relative risk reduction of between 73% to 78% when patients were consuming peanut contaminated packaged food products. So that clearly is significant. And you can see this graph on the right. This is sort of the baseline curve where patients are having reactions to lower doses and higher percentages and this, this shift to the right, which means you need more food to have a reaction and less patients are experiencing their reactions to accidental exposures. So, in summary, for epicutaneous immunotherapy, there is lower efficacy, but that increases over time. There’s a longer treatment period required to achieve similar levels in OIT. So you need probably two to three years variable, but generally higher amounts are tolerated over time and there are less side effects which are mostly cutaneous. There is a protective effect against accidental exposures, there’s improvement in quality of life and again, there are no practical limitations. There are frequent skin side effects, although they don’t seem to induce discontinuation to a significant number of patients.
Speaker 2 (36:26)
Anaphylaxis has been noted in this type of therapy too, although the rate is much lower than OIT. And again, we don’t know what happens against large exposures. It’s not a cure and patients still need to continue carrying their epinephrine. I wanted to mention biologics for food allergy. I honestly think that we need another webinar to talk about this because there is so much research going on and there are so many different biologics that are being looked at right now to see what effect they have on food allergy therapy. And I just wanted to show you this graph because the way that biologics work is they basically disrupt sort of pro allergenic and inflammatory pathways that lead to food allergy. So we have a huge variety here. Omalizumab, of course, is well known and anti GE. Dupilumab, has already been licensed for moderate to severe Eczema and is now being trialed for food allergy and so many more. So I think that biologics will have a significant role to play in the future for food allergy therapy. And I also wanted to mention that we could potentially see combination therapies coming through as well. So OIT and biologics and there are already multiple research studies looking at this combination.
Speaker 2 (37:52)
And why are we looking at combination therapies? I think one of the main drives is because we want to make food immunotherapy safer, more efficacious, and hopefully faster as well. So OIT and biologics, like I mentioned, have already been studied for multiple food allergens and in multiple research studies. I recently saw a very interesting study that is in press right now combining OIT with Premedication with antihistamines. The reason for this was to reduce side effects during OIT when using Premedication with antihistamines. It’s a small study coming from Canada it only had about 40 patients on it that was split into three groups. One was OIT with premedication antihistamines, the second was OIT with placebo antihistamines, and the third was placebo placebo. And it was quite interesting because it did show a sort of modest effect of reduction in symptoms like urgearian, abdominal pain, but it also showed an increase in certain side effects like tiredness and sleepiness, which affected quality of life. So the investigators were not really suggesting Premedication with antihistamines at this point in time. But it’s a very small study, so we are looking to see other ones potentially even using different combination antihistamines in the future.
Speaker 2 (39:26)
There are also a few studies out there combining OIT and probiotics. Again, that is an interesting combination considering that most of the adverse events in OIT come from the gastrointestinal system and probiotics may have an effect. And the most recent study looking at OIT and probiotics from Australia actually did show that there is some improvement in GI symptoms with the use of probiotics. But this was mostly noted in the younger ages, sort of children between the age of one to five. And of course, other treatments are in the pipeline, such as fecal transplants and microbiome manipulation, which are all very interesting. And I honestly think the future of food algae is looking very interesting and hopefully very bright for our patients. So we have all of these therapies now either already approved or coming through the pipeline. And sometimes having too many options can be a bit problematic because our patients are going to be faced with a decision to choose. It’s not an easy decision and we need to help them. And I really like this model of shared decision making from the Ottawa Hospital Research Institute, mainly because it kind of shows the key roles of each person in the shared decision making process.
Speaker 2 (40:46)
So as clinicians, we’re on the left and we have a responsibility for diagnosing the patient problem correctly. So if someone doesn’t have peanut allergy, they really do not need peanut immunotherapy. This is important to note we have to make sure that the patient we have in front of us actually has the disease we’re treating them for. It’s important for us to also discuss options of therapy. We can’t assume the patients know about them. Some will come very well informed and very well educated, some will know less. So it’s our responsibility to present all the options. We also need to see how ready they are to make a decision. And if we find that they really are not, we can refer them for decision support. And there is a role here for decision coach that doesn’t necessarily have to be a physician. I think nurses, dietitians, all of our colleagues in different specialties can help us with this. And then the patient role. The patient role is on the right and it is equally important to the physician role because the patients are going to tell us what they want out of this, what their goals are, and they need to be able to identify them and communicate them well.
Speaker 2 (42:02)
And their decisions will mainly be shaped by the values, priorities and also social circumstances. So, for instance, there’s no real point of sensitizing someone to say walnut if they never eat it or if a family never eats it. So we need to keep all of these things in mind and the patients have to have a very active role in this process. And hopefully the result of the shared decision making is to make an informed decision that is ideal for each patient individually and it is based on their priorities and their values. I’m going to stop here because I really want to leave time for questions and I want to thank you all for listening to me today.
Speaker 1 (42:48)
Oh, thank you so much. That was so interesting. There’s so many interesting options these days that we didn’t used to have and I think it’s wonderful to hear about them. So we do have some questions in our question box. And if you are listening, please feel free to add your questions to the box. Our first question is what is the equivalent of about 1000 to 2000 milligrams when you’re talking about peanuts? What is that dose in real life peanuts?
Speaker 2 (43:22)
Yeah, that is an excellent question and one that is not very easy to answer because the amount of protein that is inside any food and since we’re talking about peanut, let’s just talk about peanuts. Depends on the size of it. So larger peanuts will have more protein inside than smaller peanuts. So when I usually present sort of the results of this trial, I sometimes make the distinction between the European studies and the US. Studies because in Europe, the size of peanuts is much smaller and you have approximately 150 milligrams inside each sort of small peanut. And one peanut is two peanut kernels joined together. Just so we’re all speaking the same language here, but when you look at US. Peanuts, they’re much larger, right? They’re a different variety. So actually the average US. Peanut probably has about 200 to 250 milligrams of protein inside it. So if you think it like that, 1000 milligrams of peanut protein would be equivalent to four sort of medium to large size US. Grown peanuts.
Speaker 1 (44:29)
I didn’t realize that European peanuts and US. Peanuts were different sizes. That’s fascinating. That’s something I never actually thought about. So our next question is, is there a standardized guideline or protocol for oral immunotherapy?
Speaker 2 (44:48)
So there is an FDA approved product out right now that actually comes with a standardized dosing schedule that people can use. When you look into the research studies, there are many different protocols and that is of course a difficulty, I guess, for a lot of people because they may go into PubMed or other sort of resources, try to find different studies, and each study does things a little bit differently, but the overall concept is the same. So when my patients come into my office with a whole pack of copies from research studies that they have found online about oral immunotherapy, I say to them that the main concept of oral immunotherapy is to start low and go slow. And the most important part for their end is compliance and making sure that the child is taking a daily dose. So there’s no kind of common protocol that all investigators around the world have used. Everybody is doing things slightly differently. Even maintenance doses can be different. So some studies aim for 300 milligrams for maintenance. Other studies have looked at, say, 1 gram or 3 grams or 4 grams. So there is sort of a variation, but the principle behind doing it is the same.
Speaker 2 (46:12)
I hope this is helpful.
Speaker 1 (46:14)
Yes, I think what the listener was looking for was there some set protocol that they could use in their office to use for oral immunotherapy. And it sounds like there are variations in that.
Speaker 2 (46:30)
Yes, that’s correct. And like I said, the FDA approved product does have its own protocol that comes with it.
Speaker 1 (46:38)
Thank you so much. Our next question is from a patient. She said, I am a parent of a son who is EOE. He is allergic to tree nuts. Are there any promising studies for tree nut immunotherapy?
Speaker 2 (46:52)
So, yes, at the moment, a lot of researchers are also looking into trina immunotherapy. There are also biologics that I have seen looking into changes in the threshold of trina allergy with or without the combination of immunotherapy. So it’s not just peanut that has been studied. It’s just that it’s one of the most common allergies that people have looked at and have investigated, mainly because it is associated with a high risk, obviously, of severe reactions. And it is one of those allergens that scare everyone because it has been associated with fatalities, et cetera, et cetera. So studies in various forms of immunotherapy, not just OIT, have looked at peanuts, tree nuts, have looked at milk, egg, wheat, sesame. So basically the whole variety of the most common food allergens. If someone has EOE to the food that they are looking to treat with immunotherapy, this can be a little complicated, but this is probably a discussion for offline.
Speaker 1 (48:05)
Okay, some of these questions are long, and I’m hoping that I’ll be able to communicate them appropriately. So our next question says with respect to biologics, and now with more kids on deploy, map, in particular for Eczema, what is the current thought about as past oral food challenge while on dupilumab and how to approach the food when a decision to stop dupilumab arises in the future? For instance, should patients avoid the food until passing a challenge off of dupilumab?
Speaker 2 (48:38)
Okay, so if I understand this question correctly, what is being asked here is that the patient is receiving a biologic for another atopic condition that is not their food allergy. But the listener is asking whether taking the polymap will also have an effect on their food allergy and therefore what to do with the food. So, I hope I understand the question correctly, but it’s what I think it.
Speaker 1 (49:06)
Says, but I hope we both understand it.
Speaker 2 (49:10)
That’s fine. It is such an interesting question, right? Because one of the sort of really large benefits of biologics is that they are not allergen specific. So when we talk about immunotherapy to say peanuts, we are only treating peanuts. When we do immunotherapy for milk, we’re only treating milk. But potentially, because the biologic is not food allergen specific when using it, it can have an effect on multiple food allergies. So, to answer the question more directly, it is possible that using the dupilumab has also an effect on food allergies. And happily, we won’t have to guess for very long because right now the dupilumab is being researched as therapy, both as monotherapy for food allergy, but also as a combination therapy together with immunotherapy. So we will have a definitive answer to this question very soon. But let me just speculate here that using the diploma also has an effect on the food allergy. And yes, it is possible to do a food challenge while the patient is taking the diploma and actually see what level of what threshold of reactivity they have the specific food. Now, of course, once you stop the biologic, after a few half lives, you probably won’t have the effect of the biologic anymore.
Speaker 2 (50:39)
And the patient is not desensitized because in order to become desensitized, you need to have exposure to your food allergen. So again, speculating as the effect of the biologic weighs, the effect that it also has on the food allergy most likely will wane as well. So I hope I’ve answered that question correctly. What people are thinking is whether you could actually start immunotherapy in combination with the biologic. This was the combination therapy that I alluded to before. And then once you stop the biologic, you will continue your immunotherapy. So you will have that level of desensitization to fall back on and then you won’t necessarily need both forever.
Speaker 1 (51:30)
Okay, thank you. Our next question is what group of patients do you offer oral immunotherapy to?
Speaker 2 (51:39)
So, oral immunotherapy can be offered to pretty much patients with any severity of the food allergy. I think it is more interesting to think of patients that cannot have it, right? So having active EOE to the food is one contraindication. So the studies have not really included patients with EOE to the food because the idea is that if you already have active disease, if we start giving you more of the food that you have trouble with, it won’t work and it will give you more symptoms and it would potentially worsen your EOE. So that’s one sort of contraindication. Another contraindication is having sort of severe or uncontrolled auto comorbidity. So if you have very severe uncontrolled asthma, allergic rhinitis or eczema, then it is likely that oral immunotherapy will not be successful and make these diseases even worse. I also think that it is pretty important to look at this in terms of compliance. So if you have someone in front of you who you know is not going to be taking a daily dose because they have a chaotic lifestyle, or they are just too busy, or they are not able to be compliant with, say, their asthma medication, this is a big red flag.
Speaker 2 (53:07)
And I don’t think that it is a very good idea to initiate OIT in these patients, mainly because they won’t adhere to it, most likely, or they will be kind of not careful with dosing and they may end up skipping more doses, missing lots of doses and then having more problems than benefits through this therapy. So to come back to the question, OIT can actually be beneficial for a very large variety of patients with some caveats and some exceptions and it is the physician’s responsibility to actually identify that when they first evaluate the patient in the clinic. And of course, most of all patients that have positive skin testing or positive Ige to the food but are eating the food don’t need immunotherapy because I have heard some very interesting stories about that.
Speaker 1 (54:06)
Thank you so much. Our next question, you’ve touched on parts of it, but I want to go ahead and ask it for our listener. Does the research on peanuts transfer to other allergens such as eggs or milk or do allergen specific studies need to be done?
Speaker 2 (54:22)
So in terms of immunotherapy, yes, allergen specific studies need to be done, but actually, to be fair, a lot of those have already been done. So when you look in the literature, like I mentioned before, it’s not just peanut, I just started with a peanut because it’s the most studied. But there are milk immunotherapy studies, egg immunotherapy studies, all the allergens that I mentioned before, tree nuts allergies also have been researched. So there is a variety out there and in theory you should be able to desensitize to any food.
Speaker 1 (54:56)
Well, thank you so much, I appreciate that. I wish we could get to absolutely every question, but we are getting short on time. So thank you so much everyone for writing in your questions and for listening today. So I would like to thank Dr I’m going to mess your last name up sometime today, I don’t know if it’ll be right now, but I’d like to thank Dr. Aikaterini Anagnostou very much for everything she shared today and I’d like to thank our listeners for listening today. So at this time, please download the Sip certificate of attendance from your control panel and if you have any difficulties, please email us using the link in your emails. If we can go forward a couple of slides, I’d like to ask you to please join us for our next Advances in Allergy and Asthma webinar as we look at atopic dermatitis, which is also known as eczema, and how it presents in different colors of skin. This webinar will be on October 27 at 04:00 p.m.. Eastern time. You can register for this webinar on our [email protected], scroll to the bottom of our homepage to webinars. You can also view our recorded webinars on this page of our website.
Speaker 1 (56:12)
And we’d like to ask you to visit our website for quality guidelines based resources on allergy and asthma. Also access important medical information on allergies and asthma from our partners, the American College of Allergy, Asthma and Immunology at Allergy and Asthmarelief.org. Thank you again for joining us today. Please stay online for two to three minutes to complete the evaluation survey. This is Sally Schoessler for the staff at Allergy and Asthma network. Thank you for joining us for an important discussion on food allergy treatments and we look forward to having you join us next time on Advances in Allergy and Asthma.