Edwin Kim, MD, MS: Uncovering the Factors of Peanut Allergy Immunotherapy

Younger patients are faring better, and for longer, with sublingual immunotherapy. A leading investigator discusses what more needs to be learned in the burgeoning field.

Food allergy immunotherapy may be heavily influenced by age of initiation.

Investigators from the University of North Carolina School of Medicine reported data at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2021 Virtual Sessions last week showing sublingual immunotherapy (SLIT) initiated in children with peanut allergy aged 1-4 years old resulted in significant desensitization to the allergen and sustained unresponsiveness to allergen exposure months after ending once-daily SLIT.

The research, presented by Edwin Kim, MD, MS, builds on previous assessment of SLIT by himself and colleagues which showed the benefit and safety of the LEAP Study-informed allergen exposure treatment plan in a slightly older pediatric patient population.

With evidence that even younger patients benefit more greatly and for longer, and with the lone regulated peanut immunotherapy AR101 (PALFORZIA) being indicated for ages 4-17, Kim and colleagues are making progress on a promising pathway of research for allergen desensitization.

In an interview with HCPLive, Kim discussed the AAAAI 2021 trial results, what may drive earlier immunotherapy response, and what other allergens may be considered for research.

HCPLive: What were your thoughts on the trial outcomes?

Kim: We're so happy about this, I mean, for multiple reasons. One point I'll make right up front is the ability to go down to this young age, to me, is vitally important. Of course, I think we're trying to promote the LEAP guidelines with early introduction of peanut to try to prevent allergy. And we think that will be successful, but at the same time, we know that there's still going to be kids that are allergic. And I think with the LEAP guidelines, because of that, we're going to start capturing these kids even younger from when they're first diagnosed.

So, to be able to have treatments that we can immediately offer these kids as soon as they are diagnosed, I think is going to be really important for these kids and for their families. Number one, that comes to mind as far as trying to be able to go younger.

Then number two is this kind of hypothesis of the immune systems of these younger kids potentially being more responsive to these treatments is something we've suspected. I feel like our data is small, but seems to support that concept as well. Because our study we published in 2019, that group was on average about age 7. And we saw good effects there. But now that we go down to an average age of 2, those effects are much stronger, where we've got kids routinely eating 4000 milligrams—like 15-16 peanuts without any symptoms at all. And then a bunch of them hanging on to it for at least 3 months without any treatment, which is far stronger than what we saw with the older kids.

I think there's a lot of excitement with our own group that this is real, that this is something that really can become a benefit to these young kids in the future.

What factors do we believe are driving the increased benefit of earlier sublingual immunotherapy initiation in young children? Are there key characteristic differences between the average toddler patient versus a seven-year old?

Kim: It's in hypothesis mode right now as well. But I think a question that I still want to understand, and I think other researchers out there are thinking the same, is trying to separate out whether it's actually chronological age, or is it their IgE level, their peanut-specific testing levels? Because we do know that early on in diagnosis that your IgE level, your skin test levels, are going to likely be on the small side. And then over those first few years of life with the allergy, those numbers, oftentimes will go up until they find their final steady level or whatever you want to call it. That maintenance level.

So, not surprisingly, in our cohort, these young kids, they do have smaller IgE levels. So which one is it? Is it the age? Is it IgE? Is it both? I don't know that we know that answer just yet. But we're hoping to be able to, as we analyze the the lab stuff that we have from this cohort more in-depth, as well as other studies out there looking at the same age group. We're trying to separate that piece out. The idea that those IgE levels and the skin test change a lot in the first year or so goes back to this concept of, is their immune system more moldable? Or is it more willing to change, versus maybe when you're older, your immune system is more set.

I think those are all the thoughts that we have right now. Older kids can respond, there's no doubt about that. I don't want people to get the wrong message that you age out, and you can't get better. But at least our data seems to suggest if you can start earlier, that may give you an a slightly better and a slightly longer-lasting benefit.

What is it particularly about peanut that has made it the most promising prospect for allergen immunotherapy assessment?

Kim: The field sort of just naturally went there, and I think the main reason is that peanut is a very prevalent allergy and the numbers keep going up. But it also tends to be the one that's more severe, it tends to be the one that people don't outgrow. They really hang on to it for life. So, for all those reasons, I think it made sense that peanut is where we started.

But I would guess that more than half of the patients that we see for peanut allergy have other allergies at the same time. And there are plenty of kids out there who are allergic to other things and not peanut. So, this is very much proof that the concept works, that we're not crazy. But I think we very much need to and want to be able to expand this to to the other foods that people can be allergic to—and maybe multiple foods. Not only should we be thinking about can we do SLIT for milk, but we should be thinking can we do SLIT for milk, egg and peanut at the same time.

And there's definitely growing research looking at multiple allergens simultaneously. A lot of work coming out of Stanford is in that area using the the flours in oral immunotherapy. But when thinking about future directions for what we're doing for SLIT, that's very high on the list of how do we get this concept to other foods. I think instinctively, it seems like it should be pretty amenable to multiple foods at the same time. You just mix a bunch of liquids together and go for it. And maybe it's a lot easier than it might be to try to do an adjusted form. So that's very much a direction we want to go.