The Effect of Peanut Oral Immunotherapy on Allergic Reaction Threshold in Children

by | Apr 1, 2025 | 2025, Allergies, Infant and Children's Health, Nuts and Seeds, Recent Articles

Written by, Dr. Clara Sartor, ND, BSc. In this trial of peanut oral immunotherapy using store-bought, home-measured peanut butter versus peanut avoidance in high-threshold peanut allergy, those treated achieved significantly higher rates of desensitization with a durable response off treatment.

peanutsAn allergic reaction can be defined as a hypersensitive immune response to a substance that, in most circumstances, is considered harmless and not one to cause that intense of an immunological response in the majority of people1. Peanut allergies affect about 2% of the general population in countries of the West, with a prevalence expected to rise2 Allergic reaction symptoms can range from common and mild gastrointestinal symptoms, such as nausea and abdominal cramps to severe respiratory and circulatory involvement such as wheezing, bronchospasm, and syncope1. Given the potential severity of symptoms and that it persists as often a lifelong condition, understanding treatment options for addressing peanut allergic reactions remains critical2.

While research studies tend to report data on those with low tolerances to peanuts, being defined as a reaction with less than either 100 mg of peanut protein or half of a peanut, few studies report on those with higher tolerances. Sicherer et al. aimed to address this with a study design of a single-center, phase 2, prospective, two-group, parallel-group which used a double blinded, placebo-controlled oral food challenge (DBPCFC) for screening. The DBPCFC tested who was able to consume greater than 143 mg but no more than 5043 mg of peanut protein; this was conducted following a modified version of the PRACTALL protocol, and those with 300, 600, 1000, and 3000 mg dose reactions met eligibility criteria. Additionally, to meet the inclusion criteria, candidates must have been between the ages of 4 to 14 with a history of sensitization to peanut serum immunoglobulin E (IgE) and a recent history of peanut avoidance. Those with serum peanut IgE greater than 40 kUA/l were excluded from the study.

Once the criteria was met, individuals were randomly stratified at a 1:1 ratio into either a food ingesting group or a food avoidance group. Those in the food ingesting group underwent peanut oral immunotherapy (P-OIT) in which they were exposed to store-bought, home-measured peanut butter. Participants in the P-OIT group presented for observed ingestion of peanut butter, the dose of which was 20-35% of the cumulative reaction dose. Daily dosing was permitted if 137 mg of peanut butter, or approximately an 1/8th of a teaspoon, was well tolerated. Those in the P-OIT group would then return every 8 weeks for another observed ingestion at the higher dose for each subsequent encounter, with clearance to proceed at the higher daily dose only after having successfully and safely consumed the specified amount during the observed feeding. For participants who tolerated the full 9043 mg cumulative reactive dose during the screening DBPCFC, they were advised to ingest at least 2 tablespoons of peanut butter per week for 16 weeks, and then avoid peanut protein entirely for 8 weeks to assess a longer-term response. This was considered the clinical care path given its reflection to common eating habits. DBPCFCs were conducted in both groups; for initial outcomes, this was completed in the P-OIT group at either 8 weeks if taking a full tablespoon daily or after 72 weeks of total treatment with repeat DBPCFCs conducted in the avoidance group based on an algorithm to help ensure similar lengths for both groups. This was considered the primary outcome DBPCFC. Significant findings of the study were as follows:

  • A total of 73 participants met the inclusion criteria with 38 falling into the peanut ingestion group and 35 into the peanut avoidance group.
  • Of the 38 in the P-OIT group, 32 (84.2%) followed the primary outcome DBCFC, and of the 35 in the avoidance group, 30 (85.7%) followed the primary outcome DBCFC.
  • No participants exhibited serious adverse effects.
  • Skin prick tests demonstrated a decrease from baseline (of -2.57 mm in mean wheal diameter) in the ingestion group while no change was noted in the avoidance group.
  • In both the ingestion and avoidance group, gastrointestinal disorders comprised the most common adverse effects.
  • 100% of those in the ingestion group were able to titrate up to the full dose of 9043, compared to 20% (6/30) of those in the avoidance group, and 100% of those in the ingestion group were able to tolerate the full dose, compared to only 10% (3/30) in the avoidance group.
  • The authors estimate the success proportion as 100% for the ingestion group and 21% for the avoidance group, noting a 79% difference between the two; this is with 95% confidence interval and a p-value of <0.001.
  • Those in the treatment category could safely consume a meal-sized portion of peanut post-treatment.
  • 26 of 30 (87%) individuals in the treatment category maintained toleration of 9043 mg of peanut protein after 8 weeks of avoidance.

This study posed several imitations. The authors note the lack of demographic representation in the sample chosen as while sex was fairly represented in this pediatric group, ethnicity was not. This trial included a lower number of Black and Hispanic participants and a higher number of Asian participants than what would accurately represent the United Staters population of kids with food allergies. The authors note that in particular, the lack of Black participants is common thread found in other food allergy trials as well, suggesting a larger issue. Understanding how Black children respond to P-OIT and may benefit from peanut allergy treatment is principal given that this demographic shares a genetic link to peanut allergic response, and given their higher rate of atopy compared to other demographics3,4. Furthermore, this trial is limited by its design on several aspects. Generalizability was limited given the focus on those with higher thresholds to peanut IgE response and that it was conducted at a single site. Additionally, its design lacked the ability to mask those in each group which poses potential introduction to the placebo effect. Despite this, one can conclude store-bought, home-measured P-OIT may prove to be a more effective treatment option for those with high-threshold peanut allergies in increasing tolerability. More research is needed to address the limitations noted in this study and to elucidate potential long-term outcomes as well as unearth if this may be applicable to other allergens as well.

Source: Sicherer, Scott H., Supinda Bunyavanich, M. Cecilia Berin, Tracy Lo, Marion Groetch, Allison Schaible, Susan A. Perry et al. “Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy.” NEJM evidence (2025): EVIDoa2400306.

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Posted April 1, 2025.

References:

  1. Sadowski. JMDKAA. Allergy. 2023, July 31. https://www.ncbi.nlm.nih.gov/books/NBK545237/
  2. Lieberman JA, Gupta RS, Knibb RC, et al. The global burden of illness of peanut allergy: A comprehensive literature review. Allergy. May 2021;76(5):1367-1384. doi:10.1111/all.14666
  3. Thomas NM. Racial and Ethnic Data Reported for Peanut Allergy Epidemiology Do Little to Advance Its Cause, Treatment, or Prevention. Front Public Health. 2021;9:685240. doi:10.3389/fpubh.2021.685240
  4. Wegienka G, Johnson CC, Zoratti E, Havstad S. Racial differences in allergic sensitization: recent findings and future directions. Curr Allergy Asthma Rep. Jun 2013;13(3):255-61. doi:10.1007/s11882-013-0343-2