A groundbreaking three-year trial in Sweden has shown that a gentler, slower approach to peanut immunotherapy can transform the lives of allergic infants, allowing most to safely tolerate the equivalent of 70 peanuts while dramatically reducing the risk of serious reactions that have long been a problem with conventional treatments.
Study: Safety and efficacy of peanut oral immunotherapy in preschool children with slow escalation and low maintenance dosing: a randomized controlled trial. Image credit: triocean / Shutterstock
In a recent study published in Lancet Community Health – EuropeA group of researchers evaluated the safety and efficacy of oral peanut immunotherapy, with low maintenance doses and gradual increases in doses, in preschool children with peanut allergies.
Background of preschool peanut allergy treatment
Peanut allergy affects approximately 2% of the population in Western countries and often develops in early childhood, creating lifelong stress for families worried about accidental exposure or severe allergic reactions.
Oral immunotherapy involves regularly ingesting small amounts of peanuts, making it a promising option for building tolerance. However, many treatment protocols are associated with frequent side effects such as anaphylaxis and gastrointestinal symptoms, especially in older children receiving high doses. Young children may respond better because their immune systems are more adaptable early in development.
Safer and more practical treatment strategies are still needed to improve long-term outcomes in children.
Slow escalation dose study design
Researchers conducted an open-label, randomized, controlled trial in Stockholm, Sweden, involving 75 children aged 1 to 3 years with a confirmed peanut allergy. Eligibility was based on a positive oral peanut challenge result and detectable immunoglobulin E antibodies to peanuts (Arachis 2).
Children with a history of severe uncontrolled asthma, eosinophilic esophagitis, severe medical conditions, or 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.
The oral immunotherapy protocol involved slow dose titration every 4 to 6 weeks. Treatment was initiated at approximately one-quarter of each child’s response threshold and then gradually increased until a maintenance dose of 285 mg of peanut protein was reached. Peanut flour mixtures were provided in small quantities, and larger quantities were administered using commercially available peanut puffs (BAMBA). Parents administered the medication daily at home and recorded symptoms, medication, and goal adherence throughout the three-year study period.
Children received repeated oral peanut challenges at 1 and 3 years of age. To assess sustained nonresponsiveness, a final challenge was performed after 4 to 6 weeks of peanut avoidance. Blood samples were taken to measure immunoglobulin E and immunoglobulin G4 antibodies to peanut proteins. Side effects, treatment adherence, and allergic disease progression were also analyzed.
Peanut tolerance and immune response findings
This study demonstrated that peanut oral immunotherapy administered at low maintenance doses and slowly titrated provides strong clinical efficacy with relatively few serious side effects.
Of the 50 children assigned to treatment, 82% achieved durable nonresponse after 3 years of treatment and were subsequently not exposed to peanuts for 4 to 6 weeks. In contrast, only 12% of children in the peanut avoidance group were able to tolerate 750 mg of peanut protein by the final oral challenge.
Treated children showed significant improvement in peanut tolerance. 84% had already successfully tolerated the full challenge dose before the peanut-free period began. This indicates that strong desensitization occurred during ongoing treatment.
The amount of peanut tolerated after treatment was dramatically higher in the oral immunotherapy group. Children receiving treatment tolerated a median cumulative dose of 5000 mg of peanut protein (roughly equivalent to 70 to 80 whole peanuts), whereas children in the avoidance group tolerated only 3 mg after three years, essentially unchanged from their baseline responsiveness, making it unlikely that the allergy would resolve on its own. In a per-protocol analysis, 35 of 42 children who completed treatment tolerated the full 5,000 mg dose after a peanut-free period.
Of note, the severity of the reaction during the final challenge was significantly lower in treated children. Only 2.4% experienced a grade 5 reaction, such as anaphylaxis or difficulty breathing, compared to 25% in the avoidance group. These findings suggest that gradual exposure during early childhood may help the immune system develop durable tolerance.
Immune markers also changed significantly during treatment. In treated children, levels of peanut-specific immunoglobulin E antibodies and peanut 2-specific immunoglobulin E antibodies decreased over time, whereas levels of immunoglobulin G4 antibodies increased. These changes indicate that the immune system has become less responsive to peanut proteins after long-term treatment. Similar changes were not observed in the avoidance group. However, this study did not find a significant treatment effect on the development of other allergic symptoms such as atopic dermatitis, rhinoconjunctivitis, and asthma.
Safety, adherence, and dosing practicalities
The safety profile was significantly better compared to previous oral immunotherapy studies such as IMPACT, POSEIDON, and DEVIL. These studies enrolled somewhat different populations and used biweekly escalating doses and, in some cases, significantly higher maintenance doses.
More than 43,000 doses of peanut were administered during the trial, but only 0.7% of participants reported side effects.
The majority of adverse events were mild and included itching in the mouth, lip symptoms, eczema, and hives. Only 9% of adverse events reported were related to gastrointestinal symptoms. Additionally, none of the children developed chronic symptoms similar to those seen in patients with eosinophilic esophagitis.
Severe reactions were rare, with only 6 children experiencing 8 dose-related serious events, most occurring during the initial phase of dose escalation. Because of dose-related reactions, home administration of the epinephrine autoinjector was required only three times in two children.
Separately, six children in the treatment group received seven doses of epinephrine for reactions after accidentally ingesting other foods (milk, wheat, tree nuts), while seven children in the avoidance group had reactions due to accidental exposure to peanuts, four of which were classified as severe.
Approximately 22% of children completed three full years of treatment without experiencing moderate or severe dose-related allergic reactions. Families demonstrated strong adherence to medication, with a median of only 4.2% missing medication over a 3-year period.
The long interval between dose escalations (every 4 to 6 weeks) may have made it easier for families to manage infections, travel, and other daily activities. Dropout rates were modest, with 16% discontinuing OIT and 20% discontinuing avoidance, including 1 child who dropped out due to repeated treatment-associated anaphylaxis.
Impact of low-dose peanut immunotherapy
The results of this study showed that peanut oral immunotherapy using slow escalation doses and low maintenance doses can provide high levels of peanut tolerance while minimizing severe allergic reactions in preschool children. Early treatment, when immune plasticity increases, appears to improve both efficacy and safety. The use of commercially available peanut puffs and flexible treatment intervals also increased practicality for families and facilitated long-term compliance.
Compared to the more intensive dosing schedules and higher maintenance goals used in some current clinical protocols, this approach potentially provides a safer alternative. However, the authors acknowledged several limitations, including an open-label design that did not include a placebo group, a relatively small sample size of 75 participants, dependence on parent-reported adverse events, and differences in starting doses of follow-up challenges between groups. Generalizability is also limited to younger children who are sensitized to peanuts.
Additional studies comparing treatment schedules and compliance rates across different doses or treatment protocols are needed to refine treatment schedules and optimize long-term protection against peanut allergy.
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Reference magazines:
- Klevebro, S., Uhl, C., Konradsen, J. R., Ullberg, J., Tedner, SG, Holmdahl, I., Badolati, I., Da Silva Rodrigues, R., Sverremark-Ekström, E., Nilsson, C., and Asarnoj, A. (2026). Safety and efficacy of peanut oral immunotherapy in preschool children with slow escalation and low maintenance dosing: a randomized controlled trial. Lancet Community Health – Europe. Doi: 10.1016/j.lanepe.2026.101690, https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(26)00102-X/fulltext
