Peanut Oral Immunotherapy Boosts Tolerance in Children with High-Threshold Peanut Allergy

Scott Sicherer, MD

Credit: Food Allergy Research & Education

Phase 2 data presented as a late-breaker the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) in San Diego found that children with a “high threshold” peanut allergy had significantly greater rates of desensitization to meal-size amounts of peanut after peanut oral immunotherapy compared with children who avoided peanuts altogether.

Nearly half of patients with peanut allergies have allergen thresholds > 143 mg and are considered “bite safe.” While these higher thresholds should make the peanut allergy easier to treat, FDA-approved peanut allergies address allergen thresholds ≤ 143. Investigators, led by Scott Sicherer, MD, from Mt. Sinai School of Medicine, sought to assess peanut oral immunotherapy in children with high peanut thresholds.

“Typically, you would have said, “Oh, gee, you’re allergic to peanut, don't eat it,” Sicherer told HCPLive at AAAAI 2025. “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 a regular food.”

Participants (n = 73) aged 4 – 14 years were randomized 1:1 to either avoid peanuts altogether or to undergo peanut oral immunotherapy (n = 38) with approximately 3400 mg maintenance dose of storage-purchased, home-measured peanuts. This was ahead of an oral challenge up to 9043 mg. The primary endpoint was the difference in the proportion tolerating a 2-dose increase from baseline or 9043 mg between the avoidant and oral immunotherapy groups.

Among patients tolerating 9043 mg on peanut oral immunotherapy, investigators determined sustained unresponsiveness after 16 weeksof ad-lib ingestion, followed by 8 weeks of avoidance.

Patients on oral immunotherapy had a 100% success for ingestion, compared with 21% in the avoidant group (P < .001). 100% on oral immunotherapy and 10% avoiders tolerated 9043 mg.

In the per-protocol analysis, 86.7% on peanut oral immunotherapy continued to tolerate 9043 mg on sustained unresponsiveness. The intention-to-treat analysis showed 68.4% on peanut oral immunotherapy, compared with 8.6% in the avoidant group, achieved sustained unresponsiveness or a natural tolerance of 9043 mg (P < .0001).

Oral immunotherapy was shown to be relatively safe. The team observed treatment-related adverse events no greater than grade 1.

“Our phase 2 trial of POIT using inexpensive store-purchased and home-measured peanut products in children confirmed by OFC to have “high threshold” peanut allergy, showed significantly higher rates of desensitization to meal-size amounts of peanut compared to avoiders and a substantially durable response after ad-lib ingestion and then 8 weeks of avoidance,” investigators wrote.

References

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