Oral Immunotherapy Shows Promise for High Threshold Peanut Allergy, with Scott Sicherer, MD

At the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) in San Diego, Scott Sicherer, MD, from Mt. Sinai School of Medicine, presented the late breaker, “Randomized Trial of High Dose, Home Measured Peanut Oral Immunotherapy in Children with High Threshold Peanut Allergy.”

His team’s phase 2 trial compared the tolerance levels of peanut oral immunotherapy vs avoiding peanuts altogether in 73 children aged 4 – 11 years with a high threshold peanut allergy (> 143 mg) The study assessed whether patients on oral immunotherapy could tolerate 3400 mg of store-bought peanuts and then 9043 mg during the oral challenge.

100% of children on oral immunotherapy tolerated 9043 mg of peanuts, compared with 10% in the avoidant arm. HCPLive spoke with Sicherer at AAAAI 2025 about these promising findings.

HCPLive: What prompted this research, and does it address a significant gap in peanut allergy management?

Sicherer: All of the products that [the FDA has approved]—which are two omalizumab and also a commercial version of peanut oil immunotherapy—specifically brought people into the study if they reacted to half of a peanut or less. [This] makes sense because they're very sensitive to small amounts [and] more prone to have a reaction if there's a little bit of peanut in a cookie, a little mistake like that. But [these studies are] ignoring the half of the children who have a peanut allergy but could already eat half a peanut…who might be what we call “bite safe.”

[This group] could represent almost half of the peanut-allergic population. We figured that [they] would even be easier to treat, and maybe treatable with very simple measures, [such as] peanut butter. Something that you could just buy in the store…measure…[and] use as a medicine, except that obviously would have to be done under doctor supervision. That's what brought the study together.

HCPLive: Your trial found that participants who underwent peanut oral immunotherapy had a significantly higher rate of desensitization compared to those who avoided peanuts. What are some of the key factors that contributed to this success, and what does this mean for the future of peanut allergy treatment?

Sicherer: We randomized the group that was already identified as [having a] higher threshold, [meaning they could] eat more than half of the peanut before they would react. We randomized them to either go through this process of oral immunotherapy using home-measured amounts of peanut, but under allergy supervision versus [to] just avoid it.

The group that did not go through the…gradual increases under doctor supervision… had the same threshold at the end of the study. Some…actually showed a lower threshold than they started with. Some showed a higher threshold than they started with, but on average, they had no change. They were [often] still bite-safe, but they couldn't eat peanut butter.

For the ones who had the feeding test, all of [them] were able to eat a peanut butter and jelly sandwich worth of peanut butter—so they were basically able to eat it like regular food.

We wanted to also ask the question: is this a durable response? What would happen in real life if they stopped taking it as a daily dose? Because they were taking…a tablespoon a day as a daily dose as treatment? We had them spend 4 months eating it… so we encouraged them to have peanut butter and to hopefully have about two tablespoons a week, but we didn't give them a specific plan. We had them completely stop any peanut butter for 2 months so they wouldn't have any exposure. Then we brought them back to a feeding test, and for all the ones that came back for that feeding test, almost 90% were able to still ingest that whole peanut butter sandwich worth of peanut butter.

Typically, you would have said, “Oh, gee, you’re allergic to peanuts, don't eat it.” But with this information, you can make a very strong argument that if the family and child were interested in raising their threshold and eating the food more like regular food, although I would not call it a cure, it's still a treatment. They could go through a process that's relatively simple, not a lot of visits with the doctor, and could end up having them eat peanut butter like regular food.

HCPLive: Is there anything else you want to add about the findings?

Sicherer: The starting point here is to determine [a] threshold. Is this person sensitive to tiny amounts or not? If you don't figure that out, you would never want to apply this particular protocol. Secondly, it's important to have allergist supervision. I do worry that people will look at this and say, ‘Oh, home measured, home purchase’ [and interpreting it could mean] you just do this all on your own, like you're a family. No, that could be risky and dangerous. You have the allergy. You have to work with an allergist if you're going to approach something like this.

References

1. Sicherer, S, Bunyavanich, S, Berin, C, et al. Randomized Trial of High Dose, Home Measured Peanut Oral Immunotherapy in Children with High Threshold Peanut Allergy Journal of Allergy and Clinical Immunology, Volume 155, Issue 2, AB445

2. Derman, C. Peanut Oral Immunotherapy Boosts Tolerance in Children with High-Threshold Peanut Allergy. HCPLive. March 3, 2025. https://www.hcplive.com/view/peanut-oral-immunotherapy-boosts-tolerance-children-high-threshold-peanut-allergy. Accessed March 3, 2025.