Is SLIT a Fit for your patients? Sublingual Immunotherapy for Peanut Allergies

“I do think it's important that we understand that not all the foods are the same, and I think anyone who's seen patients in clinics understands this.” – Dr. Edwin Kim

Could sublingual immunotherapy (SLIT) be the peanut allergy solution allergists have been waiting for? In this episode, Dr. Mariam Hanna welcomes Dr. Edwin Kim, Division Chief of Pediatric Allergy and Immunology at the University of North Carolina, to dive into the science, practicality, and potential of SLIT. With a reputation for safety and ease of use, SLIT is gaining traction—but as Dr. Kim emphasizes, the evidence for other foods like milk, egg, and tree nuts remains extremely limited.

On this episode:

• What is SLIT? A low-dose therapy held under the tongue, offering bite-proof protection with minimal side effects like mouth itch, making it a low-risk option for many patients.
• Why choose SLIT? Why some patients prefer SLIT’s simplicity, including fewer restrictions on exercise and observation, compared to oral immunotherapy.
• Why peanuts? SLIT shows strong results for peanuts, but research on expanding to milk, egg, and tree nuts is still in its early stages, with unique challenges for each food.
• Who benefits most? Younger patients who thrive on routine and those seeking protection from accidental exposures without needing to eat large quantities of allergens.
• What lies ahead? Optimizing dosing for different foods, improving outcomes for patients with low thresholds, and expanding access to non-peanut allergens.

Whether you’re curious about incorporating SLIT into clinical practice or exploring its limits, this episode delivers evidence-based insights. Tune in now to see if SLIT is the right fit for your patients!

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Transcript

Dr. Mariam Hanna:
Hello, I'm Dr. Mariam Hanna, and this is The Allergist, a show that separates myth from medicine, deciphering allergies and understanding the immune system. Training for a marathon doesn't happen overnight. You don't sprint the entire distance on day one. Instead, you start small—just a few steps—building endurance over time. It takes persistence, consistency, and, most importantly, the right mindset to succeed. Your body adjusts, grows stronger, and eventually, what once seemed impossible becomes second nature—or at least I'm told.

Patients that have pursued food immunotherapy are told from the outset that this is a marathon, the finish line rather hazy. I was perhaps discouraged early on in the food sublingual immunotherapy, or SLIT, discussion after a patient I cared for on this treatment received peanut SLIT for two years with no symptoms and, when converted to the same quantity of peanut, immediately had a reaction.

After all, patients will often ask, "How much of a peanut are we getting today? How much of a peanut will we be able to have at the end?" I still can't answer what happened in this story. It's made me nervous about what goes by the term SLIT. 

Here, however, to explore this intriguing treatment is the physician whose name has itself become synonymous with peanut food sublingual immunotherapy—and all sublingual immunotherapy. It's my distinct pleasure to introduce Dr. Edwin Kim. Dr. Edwin Kim is a board-certified allergist and immunologist who serves as Division Chief of Pediatric Allergy and Immunology at the University of North Carolina School of Medicine and directs the UNC Food Allergy Initiative. Dr. Kim collaborates with KOFAR and the Immune Tolerance Network, and he leads the Pediatric Allergy and Immunology Fellowship Training Program at UNC. His research has focused on the development of novel therapeutics for food allergy, including sublingual immunotherapy.

Just this fall, I learned, he received a grant from Food Allergy Research and Education (FARE) to explore SLIT as a treatment for multiple tree nut allergies,  coming soon. Dr. Kim, thanks for taking the time out of your busy schedule to join us, and welcome to the podcast.

Dr. Edwin Kim:
Thank you, Mariam. I'm very excited to be here.

Dr. Mariam Hanna:
Okay, we're going to start with basics to get everybody on the same playing field. Let's start with what is sublingual immunotherapy for food?

Dr. Edwin Kim:
Yeah, I mean, with sublingual, the concept there is to have small amounts of that allergen that are held underneath the tongue. And the hope there—or the expectation—is that that allergen is then absorbed directly by the dendritic cells, which are specialized oral Langerhans cells in the mouth, and then goes straight to the draining lymph nodes and the rest of the immune system. And the benefit we hope of sublingual immunotherapy is that we can use much smaller doses because of that direct access to the immune system and perhaps be able to get stronger benefit with a lot better safety.

Dr. Mariam Hanna:
So when did this all start? When did people start pursuing sublingual immunotherapy for food?

Dr. Edwin Kim:
So at least as far as published reports are concerned, there really haven't been that many in general. We've done several with peanut, of course, but prior to even our peanut work, there were a couple of studies, particularly looking at peach allergy in the Mediterranean as well as hazelnut allergy in Europe. There were a couple of case reports looking at folks using actually small pieces of kiwi held under the tongue as a medication. And so those were purely case reports, but prior to that, those were really the only studies.

Then we were able to follow that up with our multiple studies of peanut sublingual immunotherapy, which was also done by the larger KOFAR group that you mentioned previously. And then another peanut study was done at Johns Hopkins University as well.

Dr. Mariam Hanna:
And how did preparing SLIT for food start initially?

Dr. Edwin Kim:
Yeah, so really this goes back to during my training at Duke University in North Carolina, and this is way back into the sort of late 2000s when a lot of this work was starting. I was working with my mentor and PI at the time, Wesley Burks, and there was a lot of interest in the general concept of immunotherapy.

We had already learned that subcutaneous—the allergy shots for immunotherapy—seemed to show a signal of benefit but at the same time had significant side effects and risks that just really didn't make it something that people thought was viable to pursue. So thinking about other routes that might make sense, that's where oral immunotherapy first became in vogue. At the same time, though, the concept of sublingual also popped up, just understanding that oral involved large volumes of allergen and that there was already an early sign that there could be significant side effects that came with that.

Dr. Mariam Hanna:
How is sublingual immunotherapy though  different from targeting low doses in oral immunotherapy? So what's big nowadays is that we have shifted our thought from targeting three grams as your final target dose to 300 milligrams, to now we have some groups that are targeting 30 milligrams.

Dr. Edwin Kim:
Yeah, this is really a critical question, and this is something that I'm not shy to bring up every single time I speak on sublingual. And unfortunately, the answer that I can give right now is I don't know for sure. So you're exactly right. We've looked at oral immunotherapy at a wide range of doses, and published doses of oral immunotherapy for peanut have gone as high as
4,000. Of course, the regulated version in the United States is 300 milligrams, but as you say, some groups have gone lower than that as well. I will say that it does seem to be an indication that more is better. So those OIT studies with the higher doses does seem to achieve higher threshold .

In particular, when I look at the data that comes from, say, the Aimmune trials where they looked at 300 milligrams, their success rate or the thresholds that they were achieving were good but maybe not nearly as good as the larger doses. And then when I jump over to our sublingual, where we're exposing patients to, say, two or even four milligrams—much lower than the 300 that's done in that Aimmune OIT study—it does seem like our results may actually be better than some of those or at least the same.

Now jumping back to your question, though, with our sublingual approach, what we have recommended to our patients is to hold it under their tongue and then swallow it. There are versions of sublingual where patients are instructed to spit it out afterward. That could be one version of a study that we do to try to get at your answer—as opposed to having them swallow, spit that out. But again, we've not done that at this point, so we don't know for sure. It is presumed that especially those youngest kids likely are swallowing it fairly quickly.

And so again, we are trying to create new ways that we can study this question to be sure that we are getting the benefit that we think we are. I will say also that we are leveraging very much the experience from environmental allergy sublingual immunotherapy, where there is some better data on looking at the actual immune cells involved in the mouth, as well as work with Steve Durham in particular demonstrating that sublingual does seem to have a strong effect, especially for grass pollen allergy.

Dr. Mariam Hanna:
Okay. Let's talk about goals of treatment. Let's split it up into short-term. So when a patient is undergoing this therapy, what are their short-term goals of doing food SLIT specifically?

Dr. Edwin Kim:
Yeah, this is such an important question, and this is actually why we're even having this conversation now in my mind. So going back to when we first started doing this work that you mentioned, we were talking about in the late 2000s—in particular, about 2009, 2010 is when some of this early work started with peanut sublingual immunotherapy. But at that time, really, the goals of treatment were different.

This was much more driven by research, less by the patients themselves. And the thought there was, well, if we're going to treat food allergy, that means we're going to cure food allergy. When it comes to sublingual, though, that was not the case at all. So it was about one-third of patients who were able to achieve this. One-third of them were better than they started but somewhere in the middle. And then one-third of them were barely better than when they had started—essentially looking like they were unchanged.

 
And so with that sort of spread of results, in a setting where we were thinking really it's all about full pass—because we're trying to cure the allergy, trying to get tolerance—suddenly sublingual sort of just fell to the side. And then that's where you see the explosion of OIT studies happen because that was really what looked like it was going to be more effective.

But then you fast forward to the last few years, and I think what you've started to see is much more of a focus on this concept of bite-proof protection. So the idea that, well, if we can cure it, that's fantastic, but short of curing it, a lot of our patients actually don't want to eat it. They really don't like the smell, the taste. And so really for them, they just want to get on with their life and just know that if there were a small accidental exposure, they would be safe from those exposures.

And so suddenly, looking at it with that lens, the results that we had from sublingual from back then—as well as now more recently—seem to suggest that, hey, you can get that with sublingual. There is a bit of a range of results, but the majority of patients are improving from baseline and likely have a level of protection that will keep them safe from these types of exposures.

Dr. Mariam Hanna:
So I was one that got frustrated with sublingual immunotherapy early because of this one patient experience, but you're telling me that that happened in a third of patients, so that's already validating to what I saw there. But when I speak about this to other colleagues, they're like, what's the long-term goal? When we do immunotherapy for aeroallergens, we're on a set course with a set defined timeframe. What about this?

Dr. Edwin Kim:
Yeah, so this question comes up for all the different immunotherapies at the moment. So even for OIT and then in the US with anti-IgE therapy with omalizumab, I think this has really forced us to ask that question of what is the long-term goal?

And I think this will very much vary by patients. I think there are some patients where their end goal is to try to get some version of the food into the diet and liberalize their diet to some extent. At the moment, I would say of all the treatments, the one that's probably closest to that is going to be OIT. So that would be the sort of patient that would veer in that direction.

But we do have patients where, again, they want something that is simple, easy to do, that can just allow them to avoid peanut but be safe from those small exposures. And so for those patients, the sublingual may be the way to go.

For some of those patients, there may be discrete periods of time where that matters. So it might be that, oh, again, while I'm in primary school where the cafeteria is not maybe cleaned as well as it needs to be, there's less oversight. That might be the time that's very, very important for that child. So the family may decide, well, let's do a treatment for this period of time and then reassess. There are going to be some families where they just want to know that reassurance, and they're just going to sign up, and that's what they want to do for a long period of time. One of the things that comes up with sublingual immunotherapy is, after a period of time, we've seen with our food challenges that many of these patients are able to achieve thresholds that are 2, 3, 4 peanuts, or even more.

And so there are going to be some patients where they want to just switch it over to some sort of food. It's much easier to access the food and, again, gives them a sense of opening up that diet. And so we have seen for many of these patients the ability to do exactly that. So after a period of maybe one, two, or even three years of treatment, being able to switch them to a small amount of peanut food and then doing well with that could be an option for some patients as well.

Then there could be some that want to officially transition into some form of OIT. So we've had that discussion where some people might use sublingual as a way to bypass some of the lower doses that are classic in an OIT protocol and then perhaps be able to start at a much higher dose of OIT and then continue to build up from there as well.

So I do think that we have many different options on the treatment side. But one thing I'll leave with here is that in our clinical research, as people's consent ended, as the protocols ended, we were not able to continue them on the sublingual immunotherapy. So all of them essentially transitioned over to food. And one thing that we did notice was a good number of those patients actually suddenly turned around after a month or two and asked to go back on the sublingual.

So I did think that that was very telling— that they realized the amount of work it takes for oral immunotherapy. We know it can work, but the restrictions on exercise, the observation periods, the stomach aches, and the nausea that oftentimes come with it—all of those things were essentially invisible to them on sublingual. And then suddenly having to actually think about this—what was essentially to them somewhat of an invisible disease—suddenly became ever present.

Dr. Mariam Hanna:
I love that you just said that what was suddenly an invisible disease was now ever present. Let's talk about what restrictions do exist. Are there any restrictions around dosing with sublingual immunotherapy?

Dr. Edwin Kim:
I mean, we try to take a common-sense approach. So we tell our patients, okay, if your child—because typically it's been with kids—if your child is sick, has a fever, just doesn't look right, it just doesn't make sense to give them the treatment. Now again, do we know that the treatment will necessarily cause allergic reactions or anaphylaxis? We don't. But that's probably the one scenario where we may just say, well, just use some common sense. If they're not up for it, there's not a reason to force it. We know that missing one or two days is not going to change anything, and you can hop right back onto the same dose when you're done, and you'll be perfectly safe.

Outside of that, though, we've not had any restrictions that we'd classically think of for OIT. So, exercise in particular—we've not had that restriction. As far as an observation period, we originally, in our earliest studies, had a 90-minute observation period, but we quickly realized that the main side effect of mouth itch typically comes on within a minute or two and is already gone by about 10 minutes. We really rarely saw much more than that. So we shrunk that observation period all the way down to 30 minutes.

Patients have admitted to me that they observe even less. I think once they get sort of comfortable within it and understand what might be a typical side effect versus a true allergic reaction, we've seen less of that as well. Patients have not necessarily had to take this on a full stomach or with a meal. Most of the time, they’ve not associated it with a meal.

So those are really, again, the key restrictions. The hot showers that sometimes are brought up for OIT—we've not seen that problem either. And then maybe most importantly is going to be that concern for eosinophilic esophagitis (EoE).

And so there too, we have had some patients complain not just of the mouth itch, but some stomach ache as well. And so those have been tracked. To date, I would say across the 150 patients that we've treated with sublingual immunotherapy, we've not seen EoE. But I do tell my patients, look, we are putting it in the mouth, and as we mentioned before, patients do swallow it after. So this medicine will pass through the esophagus.

And so I think my belief here is that if we treat enough patients, if we get up into the thousands or tens of thousands, is it going to happen? It seems like it would. It would make sense because it transits through. You're going to find a patient that is already predisposed to it.

And sure enough, in environmental sublingual immunotherapy, we have seen a couple of case reports. If I recall, I think a patient with perhaps ragweed and maybe with dust allergy—both were reported. And so I do think that it's possible. But the key point to me is that it’s going to be far, far, far less common than you might see with oral immunotherapy.

Dr. Mariam Hanna:
See, you're like selling me on this again. Wait, hold on. I'm also passionate about asthma and the importance of asthma control. Does that need to be as strictly controlled? I mean, controlling someone's asthma is always great, but does that need to be as strictly adhered to with SLIT for food? 

Dr. Edwin Kim:
Yeah, so that's a great question, and we've taken the exact same sort of common-sense approach with our patients there too. So it's not been that an automatic, "Oh, you're coughing and wheezing, you need to stop." Unfortunately, we know that's real life for a lot of these kids who may have mild to moderate asthma.

And so again, what we've told them there, though, is that uncontrolled asthma for any type of immunotherapy is going to be a risk factor for having a bigger reaction. So if the parent is sensing that that is happening, absolutely the focus is to get the asthma under control. And more often than not, that just says, "Well, I'm going to focus on that. I don't have the brain space to work on the sublingual." So they may choose to hold for a day or two, but it's not been a formal restriction that we've given to patients.

And again, it's something important for us to continue to follow, but we've not seen that. And this is a place where I can mention, of course, we can't intentionally put people in these situations. I can't tell patients, "Well, go ahead and exercise and then take your sublingual and let's see what happens."

And so really, the way we've had to study this is by working backwards. So what we've seen is, okay, the patients who do report some side effects that are more than mouth itch—then asking them, "Okay, what was going on at that time? Were you eating? Were you sick? Did you have a fever? Did you have asthma?" In those settings, we've not seen, again, exercise or asthma or even illness be part of that.

Dr. Mariam Hanna:
Okay, so now let's get into, does SLIT need to be standardized? Do we need to have a standardized pharmaceutical-grade product with exact amounts in it, or can we cocktail make it in the kitchen because hey, it's just food, and you dilute it a lot. What are your thoughts on that?

Dr. Edwin Kim:
Yeah, I'm going to disappoint you on this. We don't know. And so all I can speak to is the way we've done it so far. And so we have used these extracts that just across the many, many years of investigating in our laboratory before ever using it for treatment, we have found that this extract has been really stable.

And so the five milligrams per milliliter sort of concentration of peanut protein in there has been really rock stable. So that has allowed us, from a research point of view, to be really confident in what we are doing. But your question is a good one, because the extracts are not necessarily easy to get, or there's a cost that comes with it.

And so if there are ways to be able to do this with food, as you say, that would be spectacular and would be really good for access for patients. There have been a couple of reports, and I know many clinics are trying versions of this. So it'd be important for those clinics to be able to share this information back with everyone else so we can learn from that.

And first, with peanuts—since that's where we have the most data—I think it'd be great to be able to compare across, well, what are the different forms people are using and compare across what we've seen with our extracts, and is it the same or not? But then it'll be just as important, really—and a segue that I would like to take—is a huge unanswered question now is  the other foods, probably starting with milk, egg, and tree nuts.

Dr. Mariam Hanna:
Yeah, milk is the bane of my existence, so yes, yes, I agree. Does threshold matter in the discussion of sublingual immunotherapy? Would they be more amenable to oral immunotherapy at that point, or could they just stay on SLIT?

Dr. Edwin Kim:
I think that the main thing there is going to be the high-threshold patients probably just have more options that they could jump into quickly, the question there might be, well, do they need any treatment? Are they high enough where they could just go straight to small amounts of food? And if they can do that, that is the simplest. And so that might be a way to go, but there may be somewhere the sublingual makes sense.

And there, could we just jump to the straight full dilution? Could we just start with a maintenance dose? These are questions I very much want to be able to answer as spinoffs, because when we think about sublingual immunotherapy for environmental allergies—in particular, the tablets that are out there—they don't have a buildup period. They just go straight to the maintenance, and patients tolerate that very well.

If we could do that with sublingual, my goodness, that would simplify it even more. I mean, we already think of it as a pretty easy-to-do protocol, but that would really be fantastic.

Dr. Mariam Hanna:
Okay, so what are the patient populations that you think would benefit the most then from sublingual immunotherapy? Who are those patients?

Dr. Edwin Kim:
I do think that, generally speaking, it seems that the younger patients are going to be better for really most versions of immunotherapy in my mind. And for two reasons. I mean, one of them is going to be the data seems to suggest stronger sort of efficacy, perhaps longer-lasting immune changes if you start younger. But also, I think the younger patients are sort of in a setting with their families and in their controlled environments to be able to do an everyday type of treatment. As the patients get older, as we start to have adolescents, teenagers, and definitely once they start going to university, they get busy, and I think the daily treatments become a lot harder.

And so that's where ideally, if you can switch them to a daily treatment that is a food, that's a lot easier to do. That might be one option, but this is also the place where, in my mind, the biologics and stuff become part of the conversation.

And again, understanding that some countries have more access to biologics than others, I think that's an important factor as well. And again, this goes back to the key question you asked about goals. So if the goal of that middle school patient is just they want to do something hidden at home so that their friends don't have to know about it and can't tease them about it, but that will protect them in situations where they may get exposed to small amounts, hey, this might be a great option for them as well because it just hopefully can fit into that busy schedule better.

Dr. Mariam Hanna:
Okay. Here's the key question. Is SLIT ready for prime time?

Dr. Edwin Kim:
Yeah, so I'm heavily biased here, but I would think that we've gathered really good data, in particular around peanut. And so for peanut allergy, I do think that what we have seen from our data using extracts and then what's starting to come out as far as folks trying to do versions of this in the clinics with food forms seems to be very promising when it comes to peanut.

But I do think it's important that we understand that not all the foods are the same, and I think anyone who's seen patients in clinics understands this. So cashew is an allergy we're starting to see a lot of in our clinic, and cashew doesn't seem to behave the same as walnut.

And then you mentioned milk as something that can be troublesome in the clinic, and I would absolutely agree. Generally speaking, milk has maybe less severe reactions, but the ones that are severe are quite severe.

And so I do think that for peanut, I feel really good about where we are as far as trying to introduce this into clinic. But I do think it's going to be exquisitely important that we take our time and understand what's happening for some of these other foods, including the dose as well.

Because we have a dose that we have found to work really well for peanut, but is that going to be the same? Is it four milligrams of any food that is appropriate, or does it vary by the food? Not that we have to wait forever, but I do think that it's going to be important as people start to try this in their clinic settings to really understand and be wary that we could be getting different results, efficacy as well as safety.

And then the more that we can share back with each other, the faster we can try to get this to be ready, as opposed to relying on only academic centers or even industry to do this for us. 

Dr. Mariam Hanna:
Wow. Okay. So what are you looking for in SLIT research in this coming decade?

Dr. Edwin Kim:
The number one thing to me is going to be those other foods. I think we've known all the time, but now we're saying out loud that we know patients are allergic to far more than just peanut. And again, the milk, egg, and the tree nuts come to mind. Many patients are allergic to multiple foods.

And so I think that probably is number one on my list—trying to figure out what are the right doses? Can we expect the same safety? Can we expect the same efficacy when it comes to the other foods?

The other place that comes to mind is going to be—I mentioned the one third, one third, one third before. So we have one third of patients that, even with this tiny, tiny two milligram or four milligram dose of peanut, are easily eating five-plus grams of peanut. Amazing. Then we have a bunch of these folks that are in a good place where they might be eating two grams before they have any symptoms—clearly a treatment benefit from where they started.

But how do we get those two-gram people up to five grams? And then especially the ones that, if you do a true pre-to-post, they do seem like they got better. They do have immune changes, but that threshold—is it usable in clinic? It's right on the cusp.

And so how do we bring those patients up? Are there ways that we can sort of augment the treatment that we are already using right now? And so is it purely a dose thing?

And this is where I do wonder if the different formulations matter. And so there is a company—an industry company—that is trying to look at peanut sublingual immunotherapy. And I do wonder, with that treatment designed to stay where it is absorbed sublingually versus the food maybe, or the extracts that we're using sort of going all over the place, could that be a way that we get a stronger effect? We don't know. And so that's where those studies will be exquisitely important.

Dr. Mariam Hanna:
An exciting decade ahead. Alright, time to wrap up and ask today's allergist, Dr. Edwin Kim, for his top three key messages to impart to patients and physicians on today's topic: food sublingual immunotherapy. Dr. Kim, over to you.

Dr. Edwin Kim:
Yep. So, top three. Really, number one is going to be, I do think that sublingual immunotherapy, especially for peanut allergy, has come a long way. I think it's demonstrated that it is very simple to do. The safety is extraordinary, with mouth itch being the most common side effect that we see. And then the efficacy is far better than what we had expected. So I’m really confident that the majority of patients are going to be protected against small exposures.

The number two here would be that data has been solely with peanut at this point. And so we really do need to learn for the other foods. Do they behave the same, do they not? Again, because we know so many of our patients are allergic to multiple foods. So as we start to roll this out, it's going to be important for us to try to pull that data, share with each other, and understand how the other foods behave.

And then the last one is what we had spoken about. Number three is going to be, how do we bring up those people at the bottom? And so we know that some patients are going to have very small benefit or maybe no benefit, and are they patients that need to inherently jump to other treatments? Or are there ways, perhaps augmenting the treatment, that we can bring those folks up?

And so an exciting time where we have a treatment that I think can sit there in the conversation with OIT and anti-IgE therapy, but there are definitely some areas that are going to be important for us to be working on in the future coming up.

Dr. Mariam Hanna:
Perfect. Thank you, Dr. Kim, for joining us on today's episode of The Allergist.

Dr. Edwin Kim:
Thank you for having me. This has been fantastic.

Dr. Mariam Hanna:
This podcast is produced by the Canadian Society of Allergy and Clinical Immunology. The Allergist is produced for CSACI by PodCaft Productions. The views expressed by our guests are theirs alone and do not necessarily reflect the views of the Canadian Society.

This podcast is not intended to provide any individual medical advice to our listeners. Please visit www.csaci.ca for show notes and any pertinent links from today's conversation. The Find an Allergist app on the website is a useful tool to locate an allergist in your area.

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