Low-dose peanut immunotherapy safely desensitizes 82% of preschoolers in landmark trial

An unprecedented three-year Swedish trial has shown that a gentle, slow approach to peanut immunotherapy can transform the lives of children with allergies, enabling most people to safely tolerate the equivalent of 70 peanuts, while dramatically reducing the risk of severe reactions that have long plagued traditional treatment protocols.

Study: Safety and efficiency of peanut oral immunotherapy in preschool children with slow dosing and low maintenance dose: a randomized controlled trial.. Image Credit: Triocean/Shutterstock

In a recent study published in Lancet Regional Health – EuropeA group of researchers evaluated the safety and effectiveness of slow-dose peanut oral immunotherapy with a low maintenance dose in preschool children with peanut allergy.

Preschool Peanut Allergy Treatment Background

Peanut allergy affects about 2% of people in Western countries and often begins in childhood, causing lifelong stress for families worried about accidental exposure and serious allergic reactions.

Oral immunotherapy involves regular consumption of small amounts of peanuts and has become a promising option to increase tolerance. However, many treatment protocols are associated with frequent side effects, including anaphylaxis and gastrointestinal symptoms, especially in older children receiving higher doses. Young children may respond better because their immune systems are more adaptable during early development.

Safer and more practical treatment strategies are still needed to improve long-term outcomes for children.

Slow dose escalation trial design

Researchers conducted an open-label randomized controlled trial in Stockholm, Sweden, involving 75 children aged 1–3 years with confirmed peanut allergies. Eligibility was based on positive oral peanut challenge results and detectable immunoglobulin E antibodies against peanuts (Arachis hypogaea 2).

Children with significant uncontrolled asthma, eosinophilic esophagitis, serious medical conditions, or prior life-threatening anaphylaxis requiring intensive care were excluded from the study. Participants were randomly assigned in a 2:1 ratio to receive peanut oral immunotherapy or peanut avoidance.

Oral immunotherapy protocols use slow dose increases every 4–6 weeks. Treatment began with approximately one-quarter of each child’s response threshold, followed by a gradual increase until a maintenance dose of 285 mg peanut protein was reached. Peanut flour mixture was provided in small doses, and larger doses were given with commercially available peanut puffs (bamba). Parents provided daily doses at home and recorded symptoms, medications, and goal adherence during the three-year study period.

Children at 1 and 3 years were subjected to repeated oral peanut challenges. A final challenge was performed after 4–6 weeks of peanut abstinence to evaluate continued unresponsiveness. Blood samples were collected to measure immunoglobulin E antibodies and immunoglobulin G4 antibodies against peanut proteins. Adverse reactions, treatment adherence, and allergic disease progression were also analyzed.

Peanut Tolerance and Immune Response Conclusions

The study showed that slow-dose peanut oral immunotherapy with a low maintenance dose produced strong clinical benefits with relatively few serious side effects.

Of the 50 children assigned to treatment, 82% achieved sustained unresponsiveness after three years of therapy, followed by 4–6 weeks of no peanut exposure. In contrast, only 12% of children in the peanut-avoiding group were able to tolerate 750 mg of peanut protein by the last oral challenge.

There was a large improvement in peanut tolerance in the treated children: 84% had successfully tolerated the full challenge dose even before the peanut-free period began, indicating strong desensitization during ongoing therapy.

The amount of peanuts tolerated after treatment was dramatically higher in the oral immunotherapy group. Children receiving therapy tolerated a mean cumulative dose of 5000 mg of peanut protein, equivalent to approximately 70–80 whole peanuts, whereas children in the abstinence group tolerated only 3 mg after 3 years, which is essentially unchanged from baseline reactivity, suggesting a less natural resolution of allergy. In a per-protocol analysis, 35 of the 42 children who completed treatment tolerated the full 5000 mg challenge after the peanut-free period.

Notably, the severity of reactions during the final challenge was markedly lower in treated children: only 2.4% experienced grade 5 reactions such as anaphylaxis or breathing difficulties, compared with 25% in the avoidance group. These findings suggest that gradual exposure during early childhood may help the immune system develop lasting tolerance.

Immune markers also changed significantly during treatment. Peanut-specific immunoglobulin E antibody levels and Arachis hypogaea 2-specific immunoglobulin E antibodies declined over time in treated children, while immunoglobulin G4 antibodies increased. These changes indicate that the immune system has become less reactive to peanut proteins after long-term treatment. No similar changes were seen in the avoidance group. However, the study found no significant treatment effect on the development of other allergic manifestations, such as atopic dermatitis, rhinoconjunctivitis, or asthma.

Safety, Adherence, and Practicality of Dosage

The safety profile was remarkably favorable compared to previous oral immunotherapy studies Effect, POSEIDONAnd the devilwhich enrolled slightly different populations and used biweekly dosing and, in some cases, significantly higher maintenance doses.

More than 43,000 peanut supplements were administered during the trial, and only 0.7% of participants reported adverse reactions.

Most adverse events were mild and included oral itching, lip symptoms, eczema, or urticaria. Only 9% of reported adverse events were related to gastrointestinal symptoms; Additionally, no children developed any long-term symptoms, as was seen in patients with eosinophilic esophagitis.

Serious reactions were uncommon: only 6 children experienced 8 serious dose-related events, and most occurred during the initial dosing phase. Home administration of the epinephrine auto-injector was required only 3 times in 2 children due to dose-related reactions.

Separately, six children in the treatment group received seven epinephrine doses for reactions after accidental ingestion of other foods (milk, wheat, or tree nuts), while in the avoidance group, seven children received reactions from accidental peanut exposure, four of which were classified as severe.

About 22% of children completed the full three years of treatment without experiencing any moderate or severe dose-related allergic reactions. Families demonstrated strong adherence to doses, with only 4.2% of doses missed on average over three years.

The longer intervals between dose increases (every 4–6 weeks) likely made it easier for families to manage during transitions, travel, and other daily activities. Dropout rate was modest, 16% discontinued studies OIT And 20% discontinued use, including one child who withdrew because of repeated anaphylaxis associated with treatment.

Implications of low-dose peanut immunotherapy

The findings showed that peanut oral immunotherapy using slow dosing and low maintenance doses could provide high levels of peanut tolerance while reducing severe allergic reactions in preschool children. Early treatment during a period of greater immune flexibility improved both effectiveness and safety. The use of commercially available peanut puffs and flexible treatment intervals also increased practicality for families, making long-term adherence easier.

Compared to the more intensive dosing schedules and higher maintenance goals used in some current clinical protocols, this approach offers a potentially safer alternative. However, the authors acknowledged several limitations, including an open-label design without a placebo group, a relatively small sample size of 75 participants, reliance on parent-reported adverse events, and different starting doses leading to follow-up challenges across the groups. Generalization to young children who are sensitive to peanuts is also limited.

Additional studies comparing therapy schedules and adherence rates between different doses or treatment protocols are necessary to refine treatment programs and optimize long-term protection against peanut allergy.

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