Peanut oral immunotherapy desensitizes children with higher allergy thresholds

Key takeaways:

• The full dose of peanut protein in this study was 9,043 mg.
• More children receiving peanut oral immunotherapy vs. avoiding peanut had success in tolerating this amount.

Following receipt of increasing peanut oral immunotherapy, or home-measured peanut butter, desensitization to peanut protein in children initially able to ingest more than half a peanut was achieved, according to study results.

Lead author of this study published in NEJM Evidence, Scott H. Sicherer, MD, director of the Elliot and Roslyn Jaffe Food Allergy Institute at Mount Sinai Kravis Children’s Hospital and chief of the division of allergy and immunology in Mount Sinai’s department of pediatrics, told Healio the patients in this population are unique in that they have a higher threshold of peanut than that tested in current approved treatments.

“Commercial FDA approved peanut oral immunotherapy (P-OIT) was tested on children who reacted to about half a peanut or less,” Sicherer said. “The other FDA approved therapeutic, omalizumab, was similarly tested on those with this ‘low threshold’ of reactivity.

“Both treatments aim to increase threshold modestly, essentially to help people with peanut allergy to be what is often described as ‘bite safe’ in case of an accidental ingestion,” Sicherer continued.

Testing in individuals with a threshold over half a peanut is important because Sicherer said studies have uncovered this threshold in approximately half of those with food allergies.

“The question we asked was whether this higher threshold allergy should be treated, or if someone is already bite safe perhaps it is best to leave them alone,” Sicherer told Healio.

In the single-center, prospective, two-group, parallel-group, randomized controlled open-label phase 2 ChAllenging to Food with Escalating ThrEsholds for Reducing Food Allergy (CAFETERIA) trial, Sicherer and colleagues evaluated 73 children aged 4 to 14 years who reacted to a peanut protein challenge between 443 mg and 5,043 mg — equivalent to more than one peanut — to determine the impact of P-OIT using home-measured peanut butter (n = 38; median age, 6 years; 50% girls; 47.4% white) on desensitization when placed against peanut avoidance (n = 35; median age, 7 years; 25.7% girls; 68.6% white).

“We enrolled people with peanut IgE levels under 50 kU_A/L and used allergist-supervised oral food challenges (medically supervised gradual feeding) to identify those who could qualify as ‘higher threshold,’” Sicherer told Healio.

Individuals in the P-OIT group received a higher dose of peanut butter every 8 weeks, with 1 tbsp marking the highest dose.

“We supervised all up-dosings in person (one reaction was treated with epinephrine) and gave participants/families strict advice about how to avoid treatment-related reactions and how to recognize and treat them should they occur,” Sicherer told Healio. “Allergist’s careful and close supervision was essential.”

Researchers gave a double-blind placebo-controlled food challenge (DBPCFC) to a similar proportion of individuals from the two groups (ingestion, n = 32 [84.2%] vs. avoidance, n = 30 [85.7%]) and reported that significantly more individuals receiving P-OIT vs. avoiding peanut had success in tolerating either 9,043 mg peanut protein (about 35 peanuts) or a two-dose-level increase of peanut protein from baseline (100% vs. 21%). Notably, this result was observed in an analysis with prespecified multiple imputation for missing values.

Following a similar pattern, a greater proportion of the P-OIT group achieved tolerance of 9,043 mg of peanut protein than the avoidance group (100% vs. 10%), according to the study.

During this DBPCFC, researchers also found that those receiving P-OIT vs. avoiding peanut had lower median peanut-specific IgE (5.1 kU_A/L vs. 7.9 kU_A/L) and Ara h 2-specific IgE (2.6 kU_A/L vs. 3.3 kU_A/L).

Since all individuals from the P-OIT group given a DBPCFC tolerated the full dose of peanut protein, they could partake in the evaluation of sustained unresponsiveness, or tolerance off treatment. Of the 32 individuals, the study reported that 30 agreed to this further testing.

“We tested durability of response by having the treated children eat peanut products ‘ad lib’ for 4 months (but instructed to eat about 2 tbsp equivalent peanut per week) and then total avoidance for 2 months,” Sicherer told Healio.

Following this timeframe, researchers found that more individuals assigned to P-OIT had sustained unresponsiveness vs. individuals assigned to avoidance who had natural tolerance (n = 26 [86.7%] vs. n = 3 [10%]; total cohort, 68.4% vs. 8.6%).

According to Sicherer, this finding is significant because of the current era of personalized medicine.

“Identifying those with a ‘higher threshold’ allergy can have very significant treatment implications,” Sicherer told Healio. “Prior studies with the children having lower thresholds of allergy have not shown this level of success.”

Despite the difference in tolerance, the study noted comparable improvements in FAQL-PB questionnaire scores from baseline among those who received P-OIT (mean change, –7.78) and those who avoided peanut (mean change, –9.23).

In terms of safety, a higher proportion of individuals from the P-OIT group experienced an adverse event than the avoidance group (n = 25 [65.8%] vs. n = 11 [31.4%]). None of the individuals experienced serious adverse events. Additionally, dosing reactions did not exceed grade 1 severity, according to the study.

After dividing the adverse events by system organ class, researchers observed that the most common type of adverse event in both sets of individuals was gastrointestinal symptoms (P-OIT, 63.2% vs. avoidance, 22.9%), followed by immune system disorders (31.6% vs. 22.9%).

“This may be a very feasible, cheap and easy treatment approach for allergists to use when patients wish to undertake an active treatment,” Sicherer told Healio. “Importantly, however, one has to identify those with a ‘higher’ threshold, and there is no simple test for that.”

Looking ahead, Sicherer told Healio next steps include validating these findings in additional studies and looking into other food allergies.

“More studies are needed to address this approach for other foods,” Sicherer said. “We are also working, in the laboratory, on understanding how we can better identify people with higher threshold allergy and what determines treatment outcomes.”

Reference:

• Eating gradually increasing doses of store-bought peanut butter enables children with high-threshold allergy to safety consume peanuts. https://www.mountsinai.org/about/newsroom/2025/eating-gradually-increasing-doses-of-store-bought-peanut-butter-enables-children-with-high-threshold-allergy-to-safely-consume-peanuts. Published Feb. 10, 2025. Accessed Feb. 10, 2025.