Slow up-dosing peanut immunotherapy shows sustained tolerance in toddlers

A slow up-dosing oral immunotherapy protocol using low-dose peanut exposure enabled most toddlers with peanut allergy to tolerate peanut after 3 years of treatment, according to findings from the randomized SMACHO trial published in The Lancet Regional Health – Europe.^1,2

Investigators in Stockholm, Sweden, evaluated 75 children aged 1 to 3 years with confirmed peanut allergy, randomly assigning 50 children to oral immunotherapy (OIT) and 25 to peanut avoidance. The study assessed whether gradual dose escalation and a low maintenance dose could improve safety while maintaining treatment efficacy.

After 3 years of treatment followed by a 4- to 6-week peanut-free period, 82% of children in the OIT group tolerated at least 750 mg of peanut protein—equivalent to approximately 3.5 peanuts—without an allergic reaction, compared with 12% in the avoidance group.

Investigators also reported that many treated children tolerated substantially higher peanut exposures.

“All children who followed the protocol achieved the goal of eating 3 and a half peanuts without experiencing an allergic reaction, and most were able to consume up to 25 peanuts,” said Caroline Nilsson, associate professor at the Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and senior consultant at Sachs' Children and Youth Hospital. “We consider the treatment to be safe if it is carried out under controlled conditions in a health care setting.”

Low-dose maintenance protocol achieved high tolerance rates

Peanut allergy affects approximately 2% of individuals in Western Europe and North America and frequently persists into adulthood. Oral immunotherapy has emerged as a treatment strategy, though previous studies have raised concerns about adverse reactions during treatment.

In the SMACHO trial, treatment began with a very small peanut dose administered in the hospital before the transition to daily home dosing. Every 4 to 6 weeks, children returned for dose escalation until reaching a maintenance dose equivalent to approximately 1.5 peanuts daily. Investigators used commercially available peanut puffs for doses above 24 mg peanut protein.

“This is the first randomized study of oral immunotherapy in toddlers involving a slow up-dosing and a low maintenance dose,” said Nilsson. “The peanut puffs were easily ingested, which made the treatment simple for families to follow, and we were surprised by how positive the results were.”

Among children completing the protocol, 98% achieved sustained unresponsiveness to at least 750 mg peanut protein after the treatment-free period. Additionally, 83% tolerated the maximum challenge dose of 5000 mg peanut protein, roughly equivalent to 25 peanuts.

Investigators noted that adverse reactions during oral food challenges were generally milder in treated children compared with children assigned to peanut avoidance. Severe reactions during final food challenges occurred in 2.4% of treated children compared with 25% of children in the avoidance group.

Safety findings support supervised treatment approach

Across more than 43,000 administered peanut doses, adverse events occurred after 0.7% of doses and were primarily mild, including oral itching, lip symptoms, urticaria, and eczema.

Six children experienced 8 severe dose-related reactions during treatment, with most occurring during dose escalation. Epinephrine administration at home was reported 3 times in 2 children, all during the up-dosing phase.

“The cautious treatment approach appears to play an important role in safety, but this is not something that parents should attempt at home, as serious reactions can still occur,” said Anna Asarnoj, associate professor at the Department of Women’s and Children’s Health, Karolinska Institutet, and senior consultant at Astrid Lindgren Children’s Hospital, Karolinska University Hospital, who led the study with Nilsson.

Researchers emphasized that close medical supervision remains essential during treatment. The children in the study were identified through the Karolinska University Hospital laboratory network and treated at Sachs’ Children and Youth Hospital in Stockholm.

The investigators concluded that gradual dose escalation combined with low-dose maintenance may offer a safer alternative to more rapid escalation protocols while maintaining clinical effectiveness. They also suggested that the protocol could be feasible for broader clinical implementation.

The next phase of the research will evaluate long-term persistence of peanut tolerance and assess immunologic changes occurring during therapy.

References

1. Klevebro S, Uhl C, Konradsen JR, et al. Safety and efficiency of peanut oral immunotherapy in preschool children with slow up-dosing and low maintenance dosing: a randomised controlled trial. Lancet Reg Health Eur. Published online May 6, 2026. doi:10.1016/j.lanepe.2026.101690

2. Controlled peanut intake may reduce allergies in toddlers. Karolinska Institutet. May 6, 2026. Accessed May 7, 2026. https://www.eurekalert.org/news-releases/1126923