Dr Gerry Lee (Host): Food allergy is a complex, potentially life-threatening condition that requires a multidisciplinary approach, yet confusion persists in distinguishing. IgE and non IgE. Immediate reactions from intolerances. At the same time, advances in immunotherapies and biologics are opening new opportunities for proactive personalized care. Hello everyone. My name is Jerry Lee, and I'm an associate professor at Emberin University and the host of this three parts bitty series entitled Food Allergy, front Lines Clarifying Diagnosis, advancing Treatment.

From the American College of Allergy, asthma and Immunology, and is supported by a grant from Genentech. In this episode, we'll discuss FDA approved and emerging immunotherapies for food allergy, oral sublingual, and epi cutaneous highlighting their indications. Efficacy, safety, and role in shared decision making. I'm excited to be joined by two amazing food allergy experts in the field.

Our first expert is Dred Edward Kim. Dr. Edward Kim is an associate professor of pediatrics and chief. Of the division of Pediatric Allergy and Immunology at the University of North Carolina School of Medicine. He also directs the UNC Food Allergy Initiative Research Group, whose focus is the development of novel therapeutics for food allergy.

Edwin, welcome back to the podcast

Dr Edwin Kim: Thanks, Jerry. Happy to be here.

Dr Gerry Lee (Host): And our second expert is Dr. Julie Wang. Dr. Julie Wang is Professor of Pediatrics in Division of Allergy and Immunology at ICANN School of Medicine at Mount Sinai. Dr. Wang's research focuses on clinical trials developing new treatments for food allergies, as well as studies aimed at better understanding of how patients and their families manage food allergies and anaphylaxis in schools and other community settings.

Julie, welcome to the podcast.

Dr Julie Wang: Thanks so much for having me, Gary.

Dr Gerry Lee (Host): Okay, well, let's get started. Edwin, let's start with you. Could you give some background on immunotherapy for food algae? How is this performed and how is immunotherapy thought to work?

Dr Edwin Kim: Sure. the simplest way to think about immunotherapy is that it's, uh, form of exposure therapy. An example of this that people may be familiar with is, allergy shots for pollen allergy with. Allergy shots, we figure out what someone's allergic to. Maybe it's oak pollen, maybe it's ragweed. and then we give small amounts of it in the form of repeated shots to try to retrain the immune system to not be allergic.

We do the same thing when it comes to food and food immunotherapy. We identify what the food allergy trigger is, so maybe it's peanut or egg or milk, and then we start with a tiny exposure. The way I like to think about it is going to be an exposure that's big enough for the immune system to see, but not so big that it's gonna cause the actual allergic symptoms that we're trying to avoid.

then, we slowly march that amount up. We increase the amount of food over several months until we reach our treatment dose, and this is the dose that we call our maintenance dose. With this slow buildup, what we're trying to do is actually make the allergy cells like the mast cells and basophils that release the histamine.

We're trying to make these cells less reactive, and we call this desensitization. At the same time, we're trying to encourage the body's immune system to make protective antibodies called IgG to block the allergy and the dial down the reactive IgE antibodies. Once patients reach this maintenance dose, we recommend continuing the treatment for a period of months and maybe even for years with the hope of making these desensitization effect the longer term and the treatment long lasting.

Dr Gerry Lee (Host): Okay, thanks Edwin. julie, there are a lot of approaches to do food allergy immunotherapy. There's the oral sublingual and epi cutaneous approach. Could you review how each is done and maybe the differences with efficacy and safety?

Dr Julie Wang: Sure. So immunotherapy or exposure therapy can be done in different ways, orally, which we term as OIT sublingual, which we shorten as slit or epi cutaneous. also known as EPIs. The amount of allergen exposure with each of these roots varies quite a bit, with the largest amount of exposure possible by mouth, through OIT.

Smaller exposures through slit, and then much smaller exposures through the skin or EPIs. The amount of allergen exposure influences the efficacy and safety of each of these approaches with larger. Exposures potentially leading to efficacy much sooner, but with large exposures, there may also be a higher possibility of allergic reactions to the treatment itself.

Efficacy and safety of each of these treatment options can also vary based on patient specific factors, and these can include age, the food that we're trying to treat, baseline allergy test results, as well as how well the patient and their family adheres to treatment. So in addition, what we're recognizing is that the patient's threshold, can matter.

And what I mean by threshold is the amount of allergen exposure needed to trigger an allergic reaction. So for some people with peanut allergy. They're able to have one peanut or more before an allergic reaction occurs. On the other hand, there are other people with peanut allergy who will react to a very small fraction of a peanut, and these individuals are known to have low threshold allergy.

In our recent cafeteria study, we specifically looked at individuals with peanut allergy with high threshold, and what we wanted to see is how well OIT would work for these individuals. And what we saw was a high efficacy and higher rates of remission when we compare the results of the cafeteria study with other studies that have focused only on individuals with the low threshold peanut allergy.

And just to clarify what I mean by remission, is that these individuals were able to maintain the treatment effect even after a therapy was discontinued.

Dr Gerry Lee (Host): Okay, thanks Julie. So it sounds like immunotherapy for food allergy might be more effective in certain food allergy patients. For example, you are talking about those who had a higher threshold and can't tolerate a small amount of peanut without a reaction. Edwin, what do we know about. Other potential groups who actually might benefit most from food allergy immunotherapy.

Dr Edwin Kim: we know that immunotherapy can work in patients really in all allergic patients, but, our research has really found that younger kids' immune systems may respond stronger to it. It seems like the toddler's immune systems are still developing the allergic part. And so if we can jump in there and intervene and start immunotherapy before they reach school age, what the hope is that we can.

Stop their, IgE specific to the foods from expanding and becoming too much and too hard to handle. and so in studies looking at OIT and the sublingual and epi cutaneous in one to four year olds with peanut allergy, we found that these younger kids can reach higher thresholds after treatment than older kids on the same treat.

and importantly, you know, Julie brought up the remission concept and it seems like especially in these younger kids, this protection may last for several months after stopping the treatment, if you can get started in those early days. But I do think what's important is that, doesn't mean that these treatments are only exclusively for these younger ages.

We know that it can work in older ages, and we also know that threshold matters exactly as Julie said. but for those young kids when they're newly diagnosed. That could be a nice opportunity where their immune system is more likely to respond and also from a practical point of view, more likely to be able to build a treatment like this into their routine, because that is an important aspect as well.

And that's a place where when you have older kids that are busy, they have school and different activities, trying to find a way to make a daily treatment like this work can be harder. and so an advantage to starting young, there as well.

Dr Gerry Lee (Host): Okay, so this is a lot to put together. We have these different approaches and we also have different types of patients with various. Expectations for response, and of course the side effects for each treatment. So, Julie, if you were gonna put this all together, when you approach patients and engage in shared decision making, how do you approach that conversation?

Integrating all these things we've talked about?

Dr Julie Wang: Yeah, so shared decision making is super important because every patient and every family is different. So the first thing I want to explore with the families is an understanding of what the patient, as well as their family's goals are for treatment. Sometimes the patient and their families have slightly different goals, depending on the age of the child that you're talking to.

but what we're also looking to understand is, uh. Their lifestyle, as Edwin had mentioned. and whether there are specific preferences that could make one type of treatment more or less desirable for that specific patient and their family. So examples. if a family is interested in achieving high levels of desensitization so that they can potentially incorporate some food into their diet on a more regular basis, then OIT might fit their goals better than slit or.

On the other hand, if a family is interested in an oral approach that generally has a lower rate of systemic allergic reactions than they may prefer slit over OIT. Another scenario would be a family who's looking for treatment that is not oral because of oral aversion, or if they have specific lifestyle factors such that it would make it difficult for them to adhere to the dosing rules or surrounding OIT, such as avoiding vigorous exercise immediately after OIT dosing.

Then a treatment approach such as Epic may be more appropriate for that patient and family.

Dr Gerry Lee (Host): Okay, Edwin, do you have anything you want to add to your specific approach for immunotherapy? shared decision making.

Dr Edwin Kim: would, I would just echo what Julie said. I mean, no two food allergy patients are alike. Every family is affected in a unique way. food allergy affects each family differently. And so I think it's so important to really understand what is it about the food allergy that's a problem for that particular family or for that particular patient.

and then in that sort of background talk about, the different treatment options that are available and how they. These treatments can or can't help them get there. but again, I think it's really important to understand sort of what they're trying to achieve. What is the activity or activities that they want to do that they can't do, or what is it that they're worried about that they wanna be reassured against?

Really making sure we're starting from there. Then sort of describing the different treatments and how they may or may not fit into there, is going to be, super essential here. And I think what's also important to keep in mind is that, the best option may not be a treatment at all, but it might even be avoiding the food.

And so, of course, as parents and as caretakers are automatic inclination is to do something, we wanna get in there and make a difference than do something. but in some cases, actually avoiding may be the simpler and safer. Way to go as well. and so just to be able to talk through the different options of what we can do, and including avoidance as one of those I think is going to be really important.

and then kind of, staying up to date. So we know that we've have these treatments available that we've just talked about, but there's many more that are coming and with each new treatment, coming back to the conversation about, okay, where are we trying to get to? How close are we with what we have now?

And then these new treatments, is it safer? Is it easier? can it allow us. to eat more or things like that. And how do those fit in? And again, it may be that we keep doing what we're doing or maybe we do switch over to the new food. But shared decision making really should be this ongoing process that happens each time we see the patient.

Dr Gerry Lee (Host): Well, Edwin Julie, I really appreciate you sharing your approach on how to talk to patients about immunotherapy. This concludes part two of our three part miniseries, food Allergy Frontlines Clarifying Diagnosis. Advancing treatment. Next, we'll be covering the expanding role of biologics like omalizumab in managing complex food allergies. If you enjoyed this episode and like to hear other episodes from Allergy Talk, please visit college.ac ai.org/allergy talk.

And again, I wanna thank you for listening. My name is Jerry Lee for the American College of Allergy Asthma Immunology. Edwin and Julie, thank you again for joining and have a wonderful day.